Tumor CEA Research Articles

Prognostic factors for thermo-ablation of liver metastases in colon cancer: A Maltese perspective.

267 Background: Malta is a small Mediterranean archipelago with an annual colon cancer incidence of 300 patients per year and a cumulative 5-year overall survival of 58%. Despite major improvements in therapeutic strategies, colon cancer remains the third leading cause of cancer deaths locally with an annual mortality rate of circa 110 patients per year. Percutaneous thermal ablation of colorectal liver metastases involves exposure of metastatic deposits to temperature extremes using radiofrequency, microwave or cryotherapy. The role of this case series was to examine the prognostic value of clinico-pathological variables to provide insight into patient selection for ablative therapy. Methods: This retrospective analysis of 66 adult patients with colorectal liver oligometastatic disease who underwent thermal ablation between January 2014 and January 2022, reviews demographic and pathological criteria including tumour grade, presence of vascular invasion, mismatch repair and k-RAS & BRAF mutational status, CEA & Ca19.9 assay at time of treatment. Other parameters include metachronous versus synchronous disease, hepatic burden and concurrent chemotherapy. All these co-variables were analysed using the Cox Regression Hazard model to assess their impact on progression free- (PFS) and overall survival (OS). Results: For this patient cohort, the mean PFS and OS were 13.1 and 33.8 months. Our data indicates that most individuals experience progression within the first 10 months, with a gradual decline in PFS for the remaining individuals. A Ca19.9 level within normal limits (p=0.004, HR 0.157-0.700 95% CI) was related to an improved PFS but not OS. The presence of synchronous metastases (p=0.004, HR 0.168-0.715 95% CI) and ablation of one lesion (p=0.013 HR 0.191 (0.052-0.702 95 CI) were favourable prognostic markers for improved OS. k-RAS wt status was a prognostic adverse biomarker for PFS (p=0.002, HR 1.529, 6.686 95% CI). There was a paucity of data for BRAF and MMR status so these were excluded from the final analysis. No statistical survival benefit was noted for patients treated with chemotherapy, and other variables including gender, age, primary tumour sidedness, LVSI or CEA value. Conclusions: There are two surprising trends here- the paucity of survival benefit for the use of chemotherapy in conjunction with ablation and the worse outcome for k-ras wt tumours. We postulate that the absence of BRAF sub-stratification at the time of patient accrual, impacted statistical hazard. This case series suggests that the prognosis and survival of colorectal liver oligometastatic disease is multifactorial and complex, highlighting the need for further genomic and molecular insights.

Lipid levels and insulin resistance markers in gastric cancer patients: diagnostic and prognostic significance.

Gastric cancer (GC) is a highly heterogeneous and aggressive malignant tumor that seriously affects the life safety of people all over the world. Its early manifestations are subtle. The present study aimed to investigate the clinical significance of serum lipid profiles, insulin resistance markers including the triglyceride-glucose (TyG) index and the atherosclerotic index (AI), in GC patients. A retrospective analysis encompassed 215 GC patients and 827 healthy individuals. The study results show that the total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein levels, and the TyG index of GC patients were significantly lower than those of the control group before and after propensity score matching analysis. In the GC group, the levels of CEA, CA199, CA125, and CA724 tumor markers were higher than those in the healthy control group. Patients in advanced stages exhibited lower serum levels of serum lipids and TyG index compared to those in early stages. ROC analysis revealed that the TyG index, CA125, and CA199 combination yielded the highest positive prediction rate for GC at 98.6%. TyG index is significantly associated with the risk of adverse reactions after chemotherapy (OR = 1.104, 95% CI 1.028-1.186, P < 0.01). Multiple tumor markers and the TyG index combined detection showed correlations with five adverse reactions caused by chemotherapy (r < 0.6, P < 0.05). Preoperative lipid profiles in the serum show a strong correlation with patients diagnosed with GC. Evaluating a combination of various serum lipids and cancer markers significantly improves diagnostic precision for GC and the ability to predict chemotherapy side effects.

Self-reinforced D-MOF and autocatalytic AuPd@SnS2 dual-wavelength electrochemiluminescence biosensor for detection of ctDNA and CEA

Trace detection of circulating tumor DNA (ctDNA) and CEA is of great significance for early prevention and diagnosis of cancer. In this work, the well electrochemiluminescence (ECL) of the dual-ligand metal-organic frameworks (D-MOFs) and AuPd@SnS2 QDs nuclear-satellite conjugate was newly explored, and a dual-wavelength biosensing platform based on ECL energy transfer between D-MOFs and AuPd NPs coupled with catalytic effect of AuPd NPs on ECL of SnS2 QDs was developed for detection of trace ctDNA and CEA. Here, thanks to the ordered heterogeneous arrangement and network charge transfer of the luminescent ligand, the prepared D-MOF exhibits highly enhanced ECL without exogenous co-reactants. Target ctDNA was exponentially amplified using an entropy-driven DNA cycle amplification strategy to obtain bandage DNA, which triggered the DNA walker to connect the AuPd@SnS2 core-satellite probe to the electrode. Therefore, the ECL ratio of D-MOF and sensitized SnS2 at 535 nm and 650 nm was used to achieve ultrasensitive detection of trace ctDNA. Moreover, the specific recognition of target CEA to T1 DNA induced changes in dual-wavelength signals to achieve further detection of CEA, and ensure the accuracy of cancer analysis. The work opened up two novel ECL materials and developed a novel ECL biosensor for rapid detection of double tumor markers, providing a new way for early prevention and diagnosis of actual cancer.

Tissue factor pathway inhibitor 2 as a serum biomarker for endometrial cancer: a single-center retrospective study

BackgroundEndometrial cancer is the most common gynecological malignancy; however, there is no useful blood diagnostic biomarker. This study aimed to determine the utility of tissue factor pathway inhibitor 2 (TFPI2), a biomarker of ovarian cancer, as a diagnostic marker for endometrial cancer.MethodsWe examined serum TFPI2 levels in patients with endometrial cancer (n = 328) compared to those in healthy controls (n = 65) and evaluated the performance of serum TFPI2 levels as a diagnostic marker. We investigated the clinicopathological characteristics of patients with TFPI2-negative and TFPI2-positive endometrial cancer. Using immunohistochemistry (IHC), we examined TFPI2 expression in tumor tissues of 105 patients with type II endometrial carcinoma and evaluated the correlation between serum and tissue TFPI2 positivity.ResultsPatients with endometrial cancer had significantly higher serum TFPI2 levels than controls (196.7 pg/mL vs. 83.3 pg/mL; p < 0.001). The sensitivity and specificity were 54.3% and 95.4%, respectively (cutoff value, 191 pg/mL). Serum TFPI2 levels were significantly elevated along with the stage progression (stage I, 189.6 pg/mL; stage III, 230.9 pg/mL; stage IV, 312.5 pg/mL; p < 0.001). Patients with high-risk histology showed significantly elevated serum TFPI2 levels than those with low-risk histology (220.8 pg/mL vs. 187.7 pg/mL; p < 0.001). The positivity rate for TFPI2 was the highest among tumor markers, including CA125, CA19-9, and CEA. Serum TFPI2 and CA125 levels were almost independent (r = 0.203, p < 0.001), and the combined sensitivity increased to 58.8%. The 5-year survival rate was significantly worse in TFPI2-positive patients (≥ 191 pg/mL, n = 178) than in TFPI2-negative patients (< 191 pg/mL, n = 150) (hazard ratio, 8.22; 95% confidence interval, 2.49–27.1; p < 0.001). TFPI2 immunostaining revealed that 37.1% (39/105) of the samples were positive for TFPI2, with an IHC score of > 0. There was no significant difference in the immunostaining score according to histological type. Serum TFPI2 levels and immunostaining score showed poor agreement (kappa coefficient, -0.039).ConclusionsThe serum TFPI2 level is a promising marker for diagnosing and predicting the prognosis of endometrial cancer. No correlation exists between serum and tissue TFPI2 levels. Further multicenter clinical trials are needed to test the utility of TFPI2 as a diagnostic marker.

Extended procedure has no oncological benefits over segmental resection in the treatment of non-metastatic splenic flexure colon cancer, a population-based cohort study and a single center's decade-long experience.

To compare the oncological survival outcome between extended resections (ER) and segmental resection (SR) for non-metastatic splenic flexure tumors. A total of 10,063 splenic flexure colon cancers patients who underwent ER (n = 5546) or SR (n = 4517) from 2010 to 2018 were included from the Surveillance, Epidemiology, and End Results (SEER)-registered database. Additionally, we included 135 patients from our center who underwent ER (n = 54) or SR (n = 81) between 2011 and 2021. Survival rates were compared between groups. To reduce the inherent bias of retrospective studies, propensity score matching (PSM) analysis was performed. In the SEER database, patients in the ER group exhibited higher pT stage, pN stage, larger tumor size, and elevated rates of CEA level, perineural invasion, and tumor deposits compared to those in the SR group (each P < 0.05). The 5-year cancer-specific survival (CSS) rate was slightly lower in the ER group than in the SR group (79.2% vs. 81.6%, P = 0.002), while the 5-year overall survival (OS) rates were comparable between the two groups (66.2% vs. 66.9%, P = 0.513). After performing PSM, both the 5-year CSS and 5-year OS rates were comparable between the ER and SR groups (5-year CSS: 84.9% vs. 83.0%, P = 0.577; 5-year OS: 70.6% vs. 66.0%, P = 0.415). These findings were consistent in the subgroup analysis that included only patients with stage III disease or tumor size ≥ 7cm. Furthermore, although the number of harvested lymph nodes was higher in the ER group compared to the SR group (14.4 vs. 12.7, P < 0.001), the number of invaded lymph nodes remained similar between the two groups (0.5 vs. 0.5, P = 0.90). Similarly, our center's data revealed comparable 3-year OS and 3-year disease-free survival (DFS) rates between the two groups. ER have no significant oncological benefits over SR in the treatment of non-metastatic splenic flexure colon cancer, even for locally advanced cases.

Clinical value of serum tumor markers in assessing the efficacy of neoadjuvant chemotherapy in advanced ovarian cancer: single-center prospective clinical study.

This study aimed to assess the clinical importance of various biomarkers, including NLR, CEA, CA199, CA125, CA153, and HE4, through dynamic testing to evaluate the effectiveness of neoadjuvant chemotherapy (NACT) for individuals facing advanced ovarian cancer. This provides valuable information for tailoring treatment plans to individual patients, thereby leading to a more personalized and effective management of individuals facing ovarian cancer. The levels of NLR, CA125, CA199, CEA, CA153, and HE4 were detected before chemotherapy and after 3 courses of chemotherapy. Patients were categorized into ineffective and effective groups according to the effectiveness of NACT. To evaluate the factors influencing NACT's effectiveness in individuals facing advanced ovarian cancer, receiver operating characteristic (ROC) curves, predictive modeling, and multifactorial regression analysis were employed. In the effective group, the patients' age, maximum tumor diameter, and CEA and HE4 levels of the patients were significantly higher compared to those in the ineffective group (P <.05). Additionally, the difference in HE4 levels before and after treatment between the effective and ineffective groups was statistically significant (P<.05). Multifactorial analysis showed that age and maximum tumor diameter were independent risk factors impacting the effectiveness of NACT in individuals facing advanced ovarian cancer (P<.05). The ROC curve for predicting the effectiveness of NACT in individuals facing advanced ovarian cancer showed a sensitivity of 93.3% for NLR and a specificity of 92.3% for CA199. HE4 emerged as the most reliable predictor, demonstrating a specificity of 84.6% and a sensitivity of 75.3%. The area under the curve of the combined CA125 and HE4 assays for predicting the ineffectiveness of NACT in individuals facing advanced ovarian cancer was 0.825, showcasing a specificity of 74.2% and a sensitivity of 84.6%. The predictive capacity for the effectiveness of NACT in individuals facing advanced ovarian cancer is notably high when considering the sensitivity of NLR and the specificity of CA199. Additionally, the combination of CA125 and HE4 assays can obtain a better predictive effect, which can accurately select patients suitable for NACT, determine the appropriate timing of the interval debulking surgery (IDS) surgery, and achieve a satisfactory tumor reduction effect.

Abstract PO3-02-11: Impact of Tumor Volume on Oncologic Outcomes in Patients with T1 Breast Cancer: A Retrospective Analysis

Abstract Backgrounds: Measuring the extent of tumor cell accretion in the primary organ typically involves assessing the longest diameter, an important component of the widely employed TNM staging system. The largest tumor diameter is considered indicative of the risk of cancer metastasis and the likelihood of distant recurrences. However, relying solely on the unidimensional diameter to determine the degree of cancer cell accretion can be inadequate since each tumor has a unique three-dimensional shape, thus leading to different tumor volumes. Purpose: The aim of this study was to investigate the impact of tumor volume on oncologic outcomes in patients with T1-2 breast cancer. Method: We retrospectively reviewed the medical records of 1,018 patients diagnosed with invasive breast cancer who underwent breast-conserving surgery at Seoul National University Bundang Hospital from 2010 to 2015. Patients with multiple tumors, positive margins leading to mastectomy, or those who received neoadjuvant chemotherapy were excluded. Tumor volume was defined as the product of the length of the three axes to simplify the calculation. Recurrence-free survival (RFS) was estimated by the Kaplan-Meier analysis. Result: The median value for tumor volume was 7.502 cm³. Out of 1,018 patients, 124 patients exhibited tumor volumes greater than the median value. Higher tumor volume was associated with pathologic T stage (P &amp;lt; 0.001), pathologic N stage (P = 0.004), histologic grade (P &amp;lt; 0.001), and luminal B subtype (P = 0.008). In multivariable logistic regression analyses for recurrence, higher tumor volume (OR 3.532, 95% CI 1.708-7.303, P = 0.001), CEA elevation (OR 6.129, 95% CI 1.497-25.092, P = 0.012), pN stage (OR 2.038, 95% CI 1.005-4.132, P = 0.048), and luminal B subtype (OR 2.407, 95% CI 1.060-5.470, P = 0.036) were shown to be predictive factors for recurrence, while completion of radiation therapy (OR 0.142, 95% CI 0.050-0.402, P &amp;lt; 0.001) and completion of hormone therapy (OR 0.200, 95% CI 0.047-0.849, P = 0.029) were identified as protective factors. The 5-year RFS was significantly lower in patients with higher tumor volume compared to those with lower volume (97.4% vs. 91.9%; p &amp;lt; 0.001). In multivariable Cox regression analysis, tumor volume (HR 3.056, 95% CI 1.572-5.940, P = 0.001), CEA elevation (HR 4.934, 95% CI 1.437-16.935, P = 0.011), luminal B subtype (HR 2.336, 95% CI 1.076-5.073, P = 0.032), completion of RT (HR 0.131, 95% CI 0.053-0.325, P &amp;lt; 0.001), and completion of HTx (HR 0.199, 95% CI 0.060-0.655, P = 0.008) were identified as independent prognostic factors for RFS. Conclusion: In the current study, we showed higher tumor volume results in poorer oncologic outcomes in patients with T1-2 breast cancer. Therefore, the T stage based on tumor volume, which includes all three-dimensional measurements, can better predict the prognosis in breast cancer patients than the traditional T stage that is solely dependent on the unidimensional longest tumor diameter. Citation Format: Hyoung Won Koh, Eun-Kyu Kim, Hee-Chul Shin. Impact of Tumor Volume on Oncologic Outcomes in Patients with T1 Breast Cancer: A Retrospective Analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-11.

Abstract 2498: Assessing the clinical value of ctDNA sequencing for initial tumor profiling in metastatic colorectal cancer patients with sufficient tumor tissue

Abstract Introduction Tumor profiling including RAS, BRAF, HER2, and MSI/MMR status, is required to determine the treatment for patients with metastatic colorectal cancer (mCRC) at the time of diagnosis. While comprehensive tumor profiling using tissue-based next-generation sequencing (NGS) is increasingly adopted for initial profiling in mCRC, the role of circulating tumor DNA (ctDNA) NGS as initial testing in patients with sufficient tumor tissue is not clearly understood. We assessed the clinical value of ctDNA sequencing compared to tumor NGS in patients with newly diagnosed mCRC who have sufficient tumor specimens. Methods We prospectively enrolled consecutive patients with newly diagnosed mCRC at the National Cancer Center Korea. As per the institutional protocol for mCRC, initial tumor profiling was performed on primary tumor tissue using an in-house NGS panel (NCC PCP ver.3), which included 525 genes. For ctDNA sequencing, patients were evaluated using the AlphaLiquid®100 comprehensive cancer panel (IMBdx, Inc.), which included 118 genes, before the initiation of chemotherapy. Additionally, immunohistochemical (IHC) testing for HER2 and polymerase chain reaction (PCR)/IHC testing for MSI and/or MMR were performed to assess the accuracy of HER2 and MSI/MMR status. Results A total of 188 patients were enrolled. In 139 eligible patients, 275 potentially actionable mutations were found in 12 selected CRC-related genes (APC, TP53, KRAS, NRAS, BRAF, FBXW7, PIK3CA, ERBB2, SMAD4, NF1, EGFR, MET). Of these, 32% were found both in ctDNA and tissue; 54% were found in ctDNA only; 12% in tissue only, and 2% were discordant. For RAS/BRAF mutations, which are required for anti-EGFR treatment decisions, the concordance rate between ctDNA and tissue NGS was 83.1%, and the concordance was higher in patients with higher ctDNA concentrations. For 9 patients with potentially actionable copy number variations (CNV) in EGFR, HER2, MET, and FGFR1, 3 cases were found by both assays; 4 were found by ctDNA only, and 2 were found by tissue only. ctDNA NGS correctly predicted MSI/MMR status in 2 out of 4 patients with MSI-H/dMMR; in the 2 other patients, the MSI and MMR statuses were different, suggesting potential false positivity. In addition, the fold changes in ctDNA dynamics during treatment significantly correlated with changes in tumor size and CEA levels, as well as with droplet digital PCR copy number fold changes. In a patient with MET amplification, ctDNA NGS identified MET Y1230H as a potential acquired resistance mutation after crizotinib treatment, which responded to cabozantinib but not to capmatinib. Conclusions Initial tumor profiling using ctDNA NGS yielded outcomes comparable to those of tumor tissue NGS in guiding treatment for patients with newly diagnosed mCRC, thereby suggesting its utility as an initial profiling method in mCRC. Citation Format: Yongjun Cha, Bun Kim, Dong Woon Lee, Hyun Yang Yeo, Chang Won Hong, Kyung Su Han, Byung Chang Kim, Hee Jin Chang. Assessing the clinical value of ctDNA sequencing for initial tumor profiling in metastatic colorectal cancer patients with sufficient tumor tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2498.

Abstract 4808: Small intestinal leiomyosarcoma in a young adult

Abstract Objectives: • Outline the epidemiology of leiomyosarcoma•Identify the immunohistochemistry of a leiomyosarcoma Introduction: Primary small intestinal malignancies are rare malignancies as compared with other malignancies of the gastrointestinal tract. Here, we present a case of a jejunal leiomyosarcoma in a young adult. Case Presentation: A 23-year-old Caucasian male with GERD presented with five months of abdominal pain, intermittent nausea with non-bloody emesis, and a 20-pound weight loss. Presenting vital signs were within normal limits. Physical exam revealed conjunctival pallor with epigastric tenderness to palpation. Serology demonstrated iron deficiency anemia, hemoccult positive stool, negative CEA, CA19-9, and AFP tumor markers. HIV antigen antibody and EBV-PCR were non-reactive. CT of the abdomen and pelvis revealed markedly thickened heterogenous jejunal loop in the left hemiabdomen with associated mesenteric adenopathy and small volume pelvic ascites. EGD with push enteroscopy revealed a single, malignant appearing and ulcerated mass in the proximal jejunum. PET-CT showed a hypermetabolic, multilobulated, ill-defined mass involving multiple loops of jejunum. He underwent exploratory laparotomy with resection of a proximal jejunal mass (10x8 x7 cm), mesenteric lymphadenectomy, and a jejunojejunostomy creation. Pathology demonstrated leiomyosarcoma (pT2aN0MoG3), and he was initiated on cyclophosphamide and doxorubicin. Discussion: Primary small intestinal malignancies are rare malignancies with an incidence of less than 5% of all GI malignancies. 56 cases of GI leiomyosarcoma in adults were identified between 2000-2012 with a peak incidence between 55-59 years of age (Aggarrwal 2012). Leiomyosarcomas are soft tissue sarcomas arising from bones, tendons, blood vessels, or muscles with a spectrum of disease ranging from low-grade cutaneous lesions to aggressive lesions of internal organs with significant potential for metastasis (Pipe 2002). Diagnosis is based on immunohistochemical positivity for SMA, desmin, and h-caldesmon, and negativity for CD117, CD34, and DOG1.1, notably lacking KIT and PDGFRA mutations (Aggarwal 2012). Treatment involves surgical resection and a cost benefit analysis of adjuvant chemotherapy with (Reynolds, 2014). This case of a 23 year old, without significant risk factors, diagnosed with a jejunal leiomyosarcoma presents as one of the youngest cases ever to be reported and emphasizes the importance of recognizing the cancer in a broader range of the adult population. Citation Format: Alyssa A. Guo, Blake H. Bentley, Abigail L. Ellington, Haiyan Lu, William C. Lippert. Small intestinal leiomyosarcoma in a young adult [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4808.

Pre-analytical stability of the CEA, CYFRA 21.1, NSE, CA125 and HE4 tumor markers.

For lung cancer, circulating tumor markers (TM) are available to guide clinical treatment decisions. To ensure adequate accuracy, pre-analytical instabilities need to be known and addressed in the pre-analytical laboratory protocols. This study investigates the pre-analytical stability of CA125, CEA, CYFRA 21.1, HE4 and NSE for the following pre-analytical variables and procedures; i) whole blood stability, ii) serum freeze-thaw cycles, iii) electric vibration mixing and iv) serum storage at different temperatures. Left-over patient samples were used and for every investigated variable six patient samples were used and analysed in duplicate. Acceptance criteria were based on analytical performance specifications based on biological variation and significant differences with baseline. Whole blood was stable for at least 6 hours for all TM except for NSE. Two freeze-thaw cycles were acceptable for all TM except CYFRA 21.1. Electric vibration mixing was allowed for all TM except for CYFRA 21.1. Serum stability at 4°C was 7 days for CEA, CA125, CYFRA 21.1 and HE4 and 4 hours for NSE. Critical pre-analytical processing step conditions were identified that, if not taken into account, will result in reporting of erroneous TM results.

Primary tumor sidedness is not prognostic factor in resectable colorectal cancer liver metastasis: a retrospective observational cohort study.

Right-sided tumors have been reported to have a poorer survival rate than left-sided tumors; however, there remains debate regarding whether sidedness is an independent prognostic factor in colorectal cancer liver metastasis (CRLM). This study aimed to assess the impact of sidedness on prognosis in resectable CRLM and to identify prognostic factors. Patients who underwent liver resection for CRLM at Samsung Medical Center from January 2008 to December 2021 were included in the investigation. Overall survival (OS) and progression-free survival (PFS) were analyzed, and prognostic factors were identified. A total of 497 patients were included in the study, with 106 on the right side and 391 on the left side. The right-sided group had a higher percentage of synchronous tumors (90.6% vs. 80.3%, P = 0.020). In survival analysis, the right side showed lower 5-year OS (49.7% vs. 54.2, P = 0.305) and 5-year PFS (57.1% vs. 60.2%, P = 0.271), but the differences were not statistically significant. In the analysis of prognostic factors, synchronous tumor (odds ratio [OR], 5.01; P < 0.001), CEA (OR, 1.46; P = 0.016), and maximum tumor size of hepatic metastasis (OR, 1.09; P = 0.026) were associated with OS. In resectable CRLM, there was no difference in prognosis based on sidedness. CEA level, synchronous tumor, and maximum tumor size of hepatic metastasis were identified as prognostic factors.

A retrospective study analyzing if lymph node ratio carbon nanoparticles predict stage III rectal cancer recurrence.

Lymph node ratio has garnered increasing attention as a prognostic marker for rectal cancer; however, few studies have investigated the relationship between lymph node ratio and rectal cancer recurrence. Additionally, Carbon Nanoparticle tracking is a safe and effective strategy for locating tumors and tracking lymph nodes. However, no studies have reported the relationship between Carbon Nanoparticles and rectal cancer recurrence. Patients with stage III rectal cancer who underwent radical resection between January 2016 and 2020 were analyzed. The primary outcome was tumor recurrence. 269 patients with stage III rectal cancer were included in this study. The effects of lymph node ratio, Carbon Nanoparticles, and other clinicopathological factors on rectal cancer recurrence were assessed using univariate, multivariate analyses and the t-test. Univariate analysis determined tumor recurrence using cytokeratin 19 fragment, CA-199, CEA, N-stage, positive lymph nodes, total lymph nodes, and lymph node ratio(positive/total); with the lymph node ratio being the most relevant. Receiver operating characteristic (ROC) analysis determined lymph node ratio =0.38 as the optimal cutoff value. The analysis of lymph node ratio ≥0.38 and <0.38 showed statistical differences in three indicators: tumor recurrence, CEA, and use of Carbon Nanoparticles. Lymph node ratio is a strong predictor of stage III rectal cancer recurrence and may be considered for inclusion in future tumor-node-metastasis staging and stage III rectal cancer stratification. In addition, we found that Carbon Nanoparticles use significantly increased total lymph nodes and decreased lymph node ratio.

Method Comparison and Clinical Performance of Breast Cancer Tumor Markers on Novel Multiplex Immunoassay and Automatized LOCI Technology Platforms.

Tumor marker determinations are valuable tools for the guidance of breast cancer patients during the course of disease. They are assessed on diverse analytical platforms that may be associated with differences according to the methods applied and the clinical performance. To investigate the method dependency and clinical significance of breast cancer protein tumor markers, CEA, CA 15-3, CA 125, CA 19-9 and AFP were measured in a total of 154 biobanked samples from 77 patients with breast cancer, 10 with DCIS, 31 with benign breast diseases and 36 healthy controls using a Millipore multiplex biomarker panel (MP) and an automized version of the routinely used Vista LOCI technology. The markers were compared between methods and investigated for diagnostic performance. CEA, CA 15-3 and AFP showed good correlations between both platforms with correlation coefficients of R = 0.85, 0.85 and 0.92, respectively, in all samples, but similarly also in the various subgroups. CA 125 and CA 19-9 showed only moderate correlations (R = 0.71 and 0.56, respectively). Absolute values were significantly higher for CEA, CA 15-3, CA 125 and AFP in the Vista LOCI as compared with the MP method and vice versa for CA 19-9. The diagnostic performance for discrimination of breast cancer from healthy controls was similar for both methods with AUCs in ROC curves for CEA (MP 0.81, 95% CI 0.72-0.91; LOCI 0.81; 95% CI 0.72-0.91) and CA-15-3 (MP 0.75, 95% CI 0.65-0.86; LOCI 0.67, 95% CI 0.54-0.79). Similar results were obtained for the comparison of breast cancer with benign breast diseases regarding CEA (AUC MP 0.62, 95% CI 0.51-0.73; LOCI 0.64, 95% CI 0.53-0.74) and CA-15-3 (MP 0.70, 95% CI 0.6-0.81; LOCI 0.66, 95% CI 0.54-0.77). Both platforms show moderate to good method comparability for tumor markers with similar clinical performance. However, absolute levels in individual patients should be interpreted with care.

Inhibiting the Proliferation of Colorectal Cancer Cells by Reducing TSPO/VDAC Expression.

We aimed to explore the mechanism of the effect of remimazolam (Rem) on the proliferation of colorectal cancer (CRC) cells with CRC as a disease context. Translocation protein (TSPO) expression in CRC was determined by Western blotting and qRT-PCR in the Second Affiliated Hospital of Qiqihar Medical University from March 2019 to February 2022. TSPO-interacting proteins were predicted through string database. The proliferation was measured by CCK-8 and 5-ethynyl-2-deoxyuridine (EDU). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) and clonal colony on cells were formed to screen for the optimal concentration of Rem and to detect the viability. The expression of apoptosis-related proteins, Bcl-2 and P53, was determined by qRT-PCR and Western blotting. The effect of Rem on the expression of tumor markers, CEA and CA19-9, in CRC was examined through ELISA. TSPO expression in CRC tissues and cells was higher than that in ANT samples and normal intestinal epithelial cells. Over-expression of TSPO promoted the proliferation of HCT116 and the expression of tumor markers CEA and CA19-9 and inhibited the apoptosis of HCT116. Interference with TSPO inhibited the proliferation of HCT116 and the expression of CEA and CA19-9 and promoted the apoptosis of HCT116. 1 μg/mL Rem could inhibit the viability of HCT116, the proliferation of HCT116 and the expression of CEA and CA19-9, and improve the apoptosis of HCT116. TSPO could interact with VDAC and affect its protein expression, and Rem could inhibit the proliferation and the expression of CEA and CA19-9 through the TSPO/VDAC pathway, to promote its apoptosis. Rem affects the proliferation of CRC cells by inhibiting the TSPO/VDAC pathway.

An accurate prediction of negative lymph node metastasis with consideration of glucose metabolism in early-stage non-small cell lung cancer.

We aimed to identify risk factors in lymph node metastasis in early-stage non-small cell lung cancer (NSCLC) and predict lymph node metastasis. A total of 416 patients with clinical stage IA2-3 NSCLC who underwent lobectomy and lymph node dissection between July 2016 and December 2020 at National Cancer Center Hospital East were included. Multivariable logistic regression was performed to develop a model for predicting lymph node metastasis. Leave-one-out cross-validation was performed to evaluate the developing prediction model, and sensitivity, specificity, and concordance statistics were calculated to evaluate its diagnostic performance. The formula for calculating the probability of pathological lymph node metastasis included SUVmax of the primary tumor and serum CEA level. The concordance statistics was 0.7452. When the cutoff value associated with the risk of incorrectly predicting pathological lymph node metastasis was 7.2%, the diagnostic sensitivity and specificity for predicting metastasis were 96.4% and 38.6%, respectively. We created a prediction model for lymph node metastasis in NSCLC by combining the SUVmax of the primary tumor and serum CEA levels, which showed a particularly strong association. This model is clinically useful as it successfully predicts negative lymph node metastasis in patients with clinical stage IA2-3 NSCLC.

Real-world comparison of triplet- versus doublet-chemotherapy with bevacizumab in patients with newly diagnosed metastatic colorectal cancer (mCRC).

3574 Background: Meta-analysis of five randomized intensification trials in mCRC demonstrated an overall survival (OS) benefit of triplet chemotherapy (5FU/leucovorin, oxaliplatin, irinotecan) plus bevacizumab (Triplet/Bev) compared to doublet chemotherapy plus bevacizumab (Doublet/Bev) (HR 0.81). Guidelines recommend first-line Triplet/Bev for patients with excellent performance status and normal organ function who can withstand increased toxicity, but such patients are less represented in the real world. In this retrospective cohort study, we examine the real-world effectiveness of Triplet/Bev compared to Doublet/Bev in the U.S. Methods: We used the nationwide Flatiron Health electronic health record-derived database, comprising de-identified patient-level structured and unstructured data curated via technology-enabled abstraction from ~ 280 cancer clinics. Included were mCRC patients treated with first-line Triplet/Bev or Doublet/Bev between 10/23/14 and 10/31/22. OS by treatment was assessed using the Kaplan Meier method and adjustment for confounding variables was performed using Cox proportional hazards modeling with stabilized inverse probability of treatment weighting (IPTW). Pre-specified confounding variables included age, gender, race/ethnicity, year of metastatic diagnosis, health insurance, practice setting, KRAS/NRAS/BRAF mutation status, MMR/MSI status, synchronous/metachronous metastases, primary tumor sidedness, CEA, renal dysfunction, hepatic dysfunction, and ECOG performance status. Missing data were imputed using multiple imputation with chained equations. Results: Among 10,016 patients, 391 (3.9%) received Triplet/Bev and 9,625 (96.1%) received Doublet/Bev. Patients who received Triplet/Bev were younger (median age 52 vs 63 years) and were more likely to be treated at academic practices (27% vs 8%), to have synchronous metastatic disease (83% vs 65%), and to have KRAS/NRAS/BRAF wild-type disease (30% vs 17%). In the univariate analysis, median OS was 30.0 months (95% CI 24.7 – 34.7) in the Triplet/Bev cohort versus 23.4 months (95% CI 22.8 – 24.1) in the Doublet/Bev cohort (HR 0.73; 95% CI 0.62 – 0.85; p &lt; 0.001). In Cox proportional hazards modeling with IPTW, there was no significant difference in hazard of death between Triplet/Bev and Doublet/Bev (HR 0.92; 95% CI 0.75 – 1.12; p = 0.4). Conclusions: In this large, national, real-world population of patients with mCRC, first-line treatment with Triplet/Bev was not associated with improved survival compared to Doublet/Bev after accounting for differences in baseline patient characteristics. The benefit to Triplet/Bev observed in randomized trials does not translate well to a more heterogeneous, real-world population. Sub-group analyses including by age, tumor sidedness, KRAS/NRAS/BRAF status, and baseline CEA level will be performed.

Diagnostic significance of CA-62 cancer antigen for early detection and differential diagnosis of non-small cell lung cancer: results of the blind clinical trials

Background. The combination of several diagnostic methods is used to predict treatment outcomes, assess overall survival, and increase the positive predictive value of detecting malignant lung and bronchial tumors.&#x0D; Aim. To evaluate the diagnostic value of the CLIA-СА-62 chemiluminescence immunoassay reagent kit for the detection of early (IaIIb) and advanced (IIIac) stages of lung cancer (LC) in a double-blind clinical study and to assess the use of the CA-62 cancer antigen as a supportive decision-making tool in LC diagnosis in patients with suspicious changes on the tomogram or as a tool for pre-screening of LC prior to computed tomography (CT) to increase diagnostic sensitivity in the detection of early (I and II) stages of LC.&#x0D; Materials and methods. A blinded clinical study was conducted on 304 clinically verified serum samples, including 141 samples from patients with non-small cell LC (NSCLC), 133 healthy volunteers, and 30 chronic obstructive pulmonary disease patients. Quantification of other well-known tumor markers used in the diagnosis of LC (CEA, CA-125, CA 15-3, CA 19-9, CYFRА 21-1, NSE, and SCC), as well as the CA-62 marker in all serum samples was performed using electrochemiluminescent immunoassay Elecsys CA-125, ELECSYS CA 19-9, ELECSYS CYFRА 21-1 and ELECSYS SCC (COBAS, Roche Diagnostics GmbH, Germany, EU), enzyme-linked immunoassay CA 15-3-ELISA-BEST, CEA-ELISA-BEST, NSE-ELISA-BEST (AO Vector-Best, Russia) and chemiluminescent immunoassay CLIA-СА-62 (JVS Diagnostics, Skolkovo, Moscow, Russia).&#x0D; Results. CA-62 glycoprotein showed the highest level of expression at stage I NSCLC (12 745 U/mL) compared to other tumor markers studied and remained very high at the later stages of cancer: stage II (11 261 U/mL) and stage III (10 220 U/mL). A comparative analysis of the ROC curves of the most promising tumor markers CEA, CYFRA 21-1, SCC, and CA-62 for the entire NSCLC cohort versus all healthy volunteers and patients with chronic obstructive pulmonary disease showed a significant difference in the area under the curve between CA-62 (AUC 0.981) and other markers: CEA (AUC 0.84) CYFRA 21-1 (AUC 0.753)SCC (AUC 0.682). When detecting early stages (I and II) of NSCLC, a comparison of the sensitivity of the studied tumor markers showed the following pattern: CA-62 (92%)CEA (37%)CYFRA 21-1 (9%) and SCC (9%)NSE (4.5%)CA-125 (3%)CA 15-3 (1.5%)CA 199 (1%). In contrast to the CEA, CA 15-3, CA-125, NSE, CA 19-9, CYFRA 21-1, and SCC tumor markers, which are expressed proportionally to tumor growth, the epithelial carcinoma marker CA-62 showed the highest diagnostic indicators in the detection of LC early stages (III): sensitivity 92.5%, specificity 96.3%, positive predictive value 91.2%, NPV 97%, with 95% accuracy of LC detection with biopsy.&#x0D; Conclusion. The study results showed that in order to increase the specificity of computed tomography in diagnosing LC in patients with suspicious lesion on the CT scan on the tomogram, the use of the carcinoma-specific marker CA-62 can improve the interpretation of the localized focus visualized and increase the accuracy of differential diagnosis at the early stages of LC to 96%, thus contributing to an increase of the overall survival among patients with lung cancer. Of the entire panel of markers, only glycoprotein CA-62 showed a strong correlation with histology (kappa 0.91) in identifying the malignant process with inconclusive results of low-dose CT (LDCT). In the future, introducing the CA-62 marker to the current system for assessing the LC risk as a pre-screening for LDCT can improve the detection of early LC by reducing false-positive results. Once introduced into existing screening programs, it can help significantly reduce the number of patients who need LDCT, decreasing the workload of LDCT and reducing radiation exposure.

Clinical Value of Combined Multi-Indicator Tests in Diagnosis of Benign Ovarian.

To investigate the existence and degree of correlation between benign ovarian tumors and physiological indicators such as reproductive hormones and tumor markers. A total of 150 patients with benign ovarian tumors admitted to Jiaxing First Hospital between January 1, 2019, and May 30, 2021, were enrolled as research subjects, while 104 healthy women were enrolled in the control group. Comparative analysis of the correlation between the reproductive hormones LH, FSH, T, E2, and the tumor indicators AMH, AFP, CEA, CA125, and CA199 between the groups was performed. There was no statistical difference in LH, FSH, T, AMH, and CEA expression levels between the experimental and control groups (p≥0.05); E2, CA125, and CA199 levels were higher significantly in the experimental group than in the control group (P<0.001); AFP levels were significantly lower in the experimental group than in the control group (P<0.05). CA125 (0.762) had the highest AUC when diagnosing the value of each index of E2, CA125, and CA199 for benign ovarian tumors. CA125 had the highest sensitivity (56.7%), followed by E2 (50.0%); CA199 had the highest specificity (84.5%), followed by CA125 (83.7%). The combined diagnosis of benign ovarian tumors was performed using different combinations of the indicators. When the two indicators were combined for diagnosis, the combination of E2 + CA199 had the highest sensitivity (82.6%), whereas the combination of CA125 + CA199 had the largest AUC (0.783) and the highest specificity (86.4%). The combined diagnosis of E2+CA125+CA199 had a higher AUC than the combined diagnosis of the two indicators (0.805), with a sensitivity of 77.2%, and a specificity of 70.9%. The most relevant factors for benign ovarian tumors are E2, CA125, and CA199 and the combination of these three indicators has the highest AUC for disease prediction while increasing the detection rate of benign ovarian tumors.

The İmportance of tumor markers in patients undergoing resection for lung metastasis of colorectal carcinoma

In patients with suitable conditions, complete resection is a potential curative treatment for lung metastases of colorectal cancers (CRC). Various prognostic factors affecting survival have been reported in these patients. In our study, the prognostic significance of CEA and CA19-9 tumor markers in patients who underwent lung resection for CRC metastasis was researched. Fifty-three patients who underwent lung resection for CRC metastasis between January 2015 and July 2021 were included in the study. The relationship between preoperative and postoperative CEA and CA19-9 values, survival times, tumor size, and preoperative CEA and CA19-9 levels were investigated. Patients with high preoperative and postoperative CEA had shorter survival (OS) compared with patients with lower values (p≤0.001 and p= 0.009, respectively). Disease-free survival (DFS) was also shorter in patients with higher preoperative CEA values (p= 0.008). For patients with higher preoperative and postoperative CA 19-9 values, OS and DFS were shorter (p= 0.013 and p≤0.001) and (p= 0.042 and p≤0.001), respectively. There was a weak positive correlation between preoperative CEA value and tumor size (p= 0.008, Pearson correlation coefficient =0.360). However, a strong positive correlation between preoperative CA19-9 value and tumor size was discovered (p≤0.001, Pearson correlation coefficient =0.603). In our study, it was shown that preoperative-postoperative CEA and CA19-9 levels in patients with metastatic colon carcinoma are associated with overall survival.

Thyroid hormones as biomarkers of lung cancer: a retrospective study

Background Thyroid hormones are key regulators of several physiological processes, including differentiation, embryonic development, proliferation, and metabolism. Several prospective studies have shown a relationship between hyperthyroidism and cancer incidence; however, since the association between thyroid hormone levels and lung cancer remains controversial, this study aimed to determine the correlation between the same. Methods We retrospectively analyzed 289 patients, who were diagnosed with lung cancer at the Huzhou Central Hospital between January 2016 and January 2021, and 238 healthy subjects. The baseline clinical data of two groups were collected. The concentrations of thyroid hormones, tumor CEA, CYF, SCC, and NSE in both the lung cancer patient and healthy volunteer groups were analyzed. Student’s t-test or Mann–Whitney test was used to compare continuous variables. A chi-square test was adopted to estimate the relationship between serum thyroid hormones level and clinical characteristics of lung cancer cases. ROC curve analyses were used to determine the characteristics of thyroid hormones for recognizing lung cancer. Results The results showed that serum thyroid stimulating hormone (TSH), total thyroxine, total triiodothyronine, and free triiodothyronine (FT3) levels were significantly decreased, while free thyroxine (FT4) levels were increased in patients with lung cancer. In addition, FT3 was identified as a potential diagnostic biomarker of stage I–IV lung cancer with the area under the curve values of 0.807. What’s more, FT3 and FT4 were used in combination with CEA and were identified as potential diagnostic biomarkers of stage 0 lung cancer (Tis) with the area under the curve values of 0.774. Conclusions Our study highlights the possibility of using thyroid hormones as innovative diagnostic markers for lung cancer.