CA125 Levels Research Articles

Abstract 2497: Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for disease monitoring in patients with pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains a formidable challenge in the realm of oncology, characterized by its aggressive nature and resistance to treatment. Several therapeutic regimens have been shown to extend patient survival, but the majority of the patients become refractory to the treatments in a short period of time. Hence, it is critical to monitor a patient’s response to treatment in a timely manner so that different treatment regimens can be considered promptly. Currently, CA19-9 is the most common blood-based marker being used to monitor disease burden in patients with PDAC. However, 15-20% of patients with PDAC do not have elevated blood CA19-9 levels. In this study, we sought to determine the utility of two circulating extracellular vesicle (EV) based protein biomarkers, ALPPL2 (Alkaline phosphatase, placental-like 2) and THBS2 (Thrombospondin 2), for disease monitoring in patients with PDAC. We first established and optimized EV assays using the ExoViewTM platform for detecting and quantifying the number of ALPPL2+ or THBS2+ EVs in serum samples. We then determined the concentrations of ALPPL2+ or THBS2+ EVs in samples from healthy individuals and longitudinal samples from patients with Stage IV PDAC undergone treatment. The longitudinal samples were from 26 patients of which 16 were CA19-9 secretors (defined as >35 U/ml) and 10 were CA19-9 non-secretors (defined as <35 U/ml) that were treated with various regimens for 4-24 months with monthly blood sample collection and CT scans (a total of 305 samples). We found that the concentrations of ALPPL2+ and THBS2+ EVs are on average 1,737 and 1,113 times higher in PDAC patients than in the healthy controls, respectively. Correlation analysis using the mixed linear model showed that the concentrations of both ALPPL2+ and THBS2+ EVs significantly correlate with changes in tumor size (based on RECIST measurements) in the longitudinal samples of CA19-9 non-secretors or secretors. In CA19-9 non-secretors the correlation p values are 0.003 and 0.006 for ALPPL2+ and THBS2+ EVs, respectively, whereas in CA19-9 secretors, the p values are 0.014 and 0.016 for ALPPL2+ and THBS2+ EVs, respectively. Our data indicates that EV based ALPPL2 and THBS2 could potentially serve as biomarkers for disease monitoring in patients with PDAC. (This work was supported in part by the Dorrance Family Fund and the Flinn Foundation) Citation Format: Kuntal Halder, Gayle Jameson, Erkut Borazanci, Wei Lin, Dereck Cridebring, Daniel Von Hoff, Haiyong Han. Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for disease monitoring in patients with pancreatic ductal adenocarcinoma [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 2497.

Abstract 6884: Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract cancer

Abstract Background: The tumor microenvironment (TME) is composed of not only cancer cells but also an extracellular matrix and many types of non-cancerous cells, including fibroblasts and immune cells. In recent years, infiltrating immune cells in TME are known as a predictor of chemotherapy and immunotherapy effectiveness. The purpose of this study is to evaluate infiltrations of lymphocytes and macrophages in biliary tract cancers (BTCs). Methods: Clinical data and tissues were obtained from 130 patients who underwent surgical treatment for BTCs (intrahepatic, perihilar, and distal bile duct cancer, gallbladder cancer, and ampullary cancer) at our institution between 2001 and 2017.The immunohistochemical evaluation was performed to evaluate the number of CD8+ T cells, CD4+ T cells and FOXP3+ T cells and CD68+ Macrophages around the tumor cells. We defined Immunoscore based on the status of infiltrating immune cells. With CD8-high, CD4-high, and FOXP3-high TILs and CD68-low TAMs as one factor, the number of factors was counted in each case, and Immunoscore was assigned a score of 5 stages, from 0 to 4. It was high for the score of 3-4 and low for the score of 0-2. Also, to evaluate the correlation with TME and systemic inflammatory reaction, we examined blood inflammatory biomarker from peripheral blood samples. Results: A total of 59 cases had high Immunoscore and 71 cases had low Immunoscore. Patients with high Immunoscore showed significantly superior overall survival (OS) and recurrence free survival (RFS) than those with low Immunoscore (median OS 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p < 0.001). For OS, low Immunoscore, positive lymph node metastasis, presence of distant metastasis, and high serum CA19-9 level were independent poor prognostic factors (hazards ratio 2.05, 3.48, 1.7, and 2.05; p = 0.01, p = 0.005, p = 0.05, and p = 0.01, respectively). For RFS, low Immunoscore, T classification of pT3-4, and presence of distant metastasis were independent poor prognostic factors with hazards ratio of 2.41 (p = 0.001), 2.16 (p = 0.005), and 3.58 (p = 0.005), respectively. Patients with high preoperative Neutrophil-to-lymphocyte ratio (NLR) had a significantly lower average number of CD8+ T cells as compared to patients with low NLR (p = 0.02). Preoperative NLR was associated with infiltrating CD8+ T cells in TME. Conclusions: High Immunoscore group had significantly longer OS and RFS and was an independent good prognostic factor. Also, infiltrating CD8+ T cells in TME correlated preoperative NLR. Our findings indicated that in biliary tract cancer, the evaluation of infiltrating immune cells in TME was useful to predict patient prognosis, and preoperative NLR may predict the tumor infiltrating CD8+ T cells. Citation Format: Kousuke Hatta, Ryota Tanaka, Kenjiro Kimura, Shinpei Eguchi, Go Ohira, Hiroji Shinkawa, Kohei Nishio, Masahiko Kinoshita, Shigeaki Kurihara, Shuhei Kushiyama, Takahito Kawaguchi, Naoki Tani, Koichi Nakanishi, Mizuki Yoshida, Takeaki Ishizawa. Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract cancer [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 6884.

Does Programmed Cell Death 1 Ligand (Pd-L1) Expression Predict Recurrence in Women With Endometrioma?

The study aimed to evaluate whether there is a difference in the expression of programmed cell death 1 ligand (PD-L1) in the cell lining of endometrioma between cases with and without recurrent disease. Additionally, we sought to assess the effect of cyst size and serum CA125 level on the expression of PD-L1 staining. The pathological specimens were immunohistochemically stained for PD-L1 in women who underwent surgery for endometrioma. All patients were evaluated to confirm if their endometriomas had recurred or not. A total of 36 patients who underwent surgery for endometrioma were included. The study population was divided into two groups according to their recurrence status. The study group (having recurrence) (n=12) and the control group (having no recurrence) (n=24) were compared regarding their demographic and clinical characteristics and PD-L1 staining. PD-L1 staining and the intensity of PD-L1 staining did not differ between the patients with and without recurrence. No variable, including parity, cyst size, serum CA125 level, and PD-L1 staining, was found to be significant in determining recurrence. No significant difference was found between the groups with and without PD-L1 staining in terms of cyst size and serum CA125 level. Although we have shown that PD-L1 expression could not be used for the prediction of recurrence, further studies are needed to assess this issue and to guide the development of new immunotherapeutic agents on this basis.

Postoperative lymph node metastasis status and related factors in patients with early-stage, low-risk endometrial cancer assessed by the Mayo criteria

Objective: To investigate the postoperative lymph node metastasis status and related factors of patients with early-stage low-risk endometrial cancer evaluated by the Mayo criteria in order to make the preoperative evaluation more accurate. Methods: A total of 172 patients with early-stage low-risk endometrial cancer who underwent surgery in Sichuan Provincial Cancer Hospital from 2009 to 2018 and were evaluated as early low-risk according to the "Mayo criteria" were retrospectively enrolled, and were divided into lymph node metastasis group (7 cases) and non-metastasis group (165 cases) according to the results of postoperative pathological examination. The postoperative pathological examination results and prognosis of all patients were collected. The lymph node metastasis of the two groups was analyzed. The multiple logistic regression model was used to analyze the related factors of lymph node metastasis, and the area under the curve (AUC) of the relevant factors was calculated by using the receiver operating characteristic curve to predict the postoperative lymph node metastasis of patients. Results: The age of 172 patients was (53.0±8.6) years, and the follow-up [M(Q1,Q3)] was 64.1 (46.2, 91.4) months, among whom 2 relapsed and 1 died. Among the 7 patients with lymph node metastasis, 5 cases had pelvic lymph node metastasis, 1 case had pelvic lymph union and abdominal para-aortic lymph node metastasis, 1 case had isolated abdominal para-aortic lymph node metastasis, 3 cases had two lymph node metastases, and 4 cases had intrailiac lymph nodes being the most common metastasis site. Multivariate analysis showed that preoperative serum cancer antigen (CA) 125 was the relevant factor for postoperative lymph node metastasis, with an OR value (95%CI) of 1.022 (1.001-1.043) (P=0.042), with AUC (95%CI) of CA125 predicting lymph node metastasis of 0.850 (0.761-0.939) (P=0.002), and the optimal cut-off value of CA125 was 29.305 U/ml with the sensitivity of 85.7% and the specificity of 80.6%. Conclusions: When CA125>29.305 U/ml, patients with early-stage low-risk endometrial cancer assessed by the Mayo criteria, had an increased risk of lymph node metastasis. Therefore, adding preoperative serum CA125 level as an evaluation index on the basis of the classic "Mayo criteria" may help conduct more accurate preoperative evaluation and better identify early-stage low-risk EC patients.

A case of treatment-resistant advanced gastric cancer with FGFR2 gene alteration successfully treated with pemigatinib.

Comprehensive genome profiling (CGP) is expected to widen the scope of cancer drug options by identifying the genes involved in carcinogenesis. However, a few patients can access recommended treatments following CGP. Herein, we report a case in which pemigatinib, a selective fibroblast growth factor receptor (FGFR) inhibitor, was used as last-line therapy to treat a patient with advanced gastric cancer exhibiting FGFR2 genomic alterations, as determined by CGP testing. The patient (male, 52years old) was diagnosed with advanced gastric cancer (cStage IV, cT4aN3M1 [LYM], por, HER2 0, microsatellite stable) and received docetaxel + cisplatin + S-1 (7 cycles), irinotecan + ramucirumab (11 cycles), and nivolumab (3 cycles), but experienced progressive disease (PD). Subsequently, FoundationOne Liquid CDx testing was conducted, revealing FGFR2 rearrangement and amplification; however, no clinical trials on genotype-matched therapies for FGFR2 alterations were available. After three cycles of TAS-102, the patient experienced PD and provided consent for the off-label use of pemigatinib. The Cancer Genomics Medical Committee of our hospital approved the self-funded treatment. The patient had markedly decreased CEA and CA19-9 levels after treatment initiation, but experienced PD after five courses. Over the treatment course, grade 1 hyperphosphatemia and onychomadesis were observed. To the best of our knowledge, this is the first reported case of pemigatinib therapy employed in a patient with advanced gastric cancer exhibiting FGFR2 gene alterations. This case could serve as a notable example of tumor-agnostic therapy to broaden treatment options for gastric cancer patients with rare genetic alterations.

Malignant Brenner Tumor of the Ovary: A Systematic Review of the Literature.

Malignant Brenner tumors are rare ovarian tumors, accounting for less than 1% of malignant ovarian neoplasms. The aim of this manuscript is to systematically review the current literature concerning malignant Brenner tumors. We searched three medical databases (PubMed, Scopus, and Web of Science) for relevant articles published until 15 September 2023. After applying inclusion and exclusion criteria, 48 manuscripts describing 115 cases were included in this study from the English literature. We analyzed the demographic, clinical, pathological, and oncological characteristics of 115 patients with malignant Brenner tumors. The statistical analysis showed that recurrence was marginally statistically significantly related to tumor stage and was more common in patients with ascites and in women with abnormal CA-125 levels; patients that were treated with lymphadenectomy had better disease-specific survival.

Remarkable response to capmatinib in a patient with intrahepatic cholangiocarcinoma harboring TFG-MET fusion.

Dysregulation of mesenchymal-epithelial transition factor (MET) gene due to amplification, mutation, and fusion has been reported in various types of human cancers. Recently, the efficacy of small-molecule tyrosine kinase inhibitors (TKIs) targeting MET has been demonstrated in a wide range of MET-dysregulated tumors. The majority of biliary tract cancers including intrahepatic cholangiocarcinoma (iCCA) are diagnosed at an advanced stage, and the utility of conventional chemotherapy is limited. Here, we present a case of metastatic iCCA harboring TFG-MET gene fusion, which demonstrated a remarkable response to treatment with capmatinib, a selective MET inhibitor. The patient was a 46-year-old man diagnosed with iCCA with hepatic, intraabdominal lymph nodes, and peritoneal metastases. Comprehensive genomic profiling (CGP) revealed TFG-MET gene fusion in his tumor. After becoming refractory to standard chemotherapy, he received capmatinib, which resulted in a marked shrinkage of the liver masses and lymph node metastases, as well as a drastic decrease in serum CA19-9 level. Our case reinforces the importance of CGP in exploring targeted therapy and supports the potential role of capmatinib in the treatment of tumors harboring MET fusions.

Prognostic value of dynamic changes of pre- and post-operative tumor markers in colorectal cancer.

Colorectal cancer (CRC) prognosis assessment is vital for personalized treatment plans. This study investigates the prognostic value of dynamic changes of tumor markers CEA, CA19-9, CA125, and AFP before and after surgery and constructs prediction models based on these indicators. A retrospective clinical study of 2599 CRC patients who underwent radical surgery was conducted. Patients were randomly divided into training (70%) and validation (30%) datasets. Univariate and multivariate Cox regression analyses identified independent prognostic factors, and nomograms were constructed. A total of 2599 CRC patients were included in the study. Patients were divided into training (70%, n = 1819) and validation (30%, n = 780) sets. Univariate and multivariate Cox regression analyses identified age, total number of resected lymph nodes, T stage, N stage, the preoperative and postoperative changes in the levels of CEA, CA19-9, and CA125 as independent prognostic factors. When their postoperative levels are normal, patients with elevated preoperative levels have significantly worse overall survival. However, when the postoperative levels of CEA/CA19-9/CA125 are elevated, whether their preoperative levels are elevated or not has no significance for prognosis. Two nomogram models were developed, and Model I, which included CEA, CA19-9, and CA125 groups, demonstrated the best performance in both training and validation sets. This study highlights the significant predictive value of dynamic changes in tumor markers CEA, CA19-9, and CA125 before and after CRC surgery. Incorporating these markers into a nomogram prediction model improves prognostic accuracy, enabling clinicians to better assess patients' conditions and develop personalized treatment plans.

Cox model risk score to predict survival of intrahepatic cholangiocarcinoma after ultrasound-guided ablation.

To explore factors associated with overall survival (OS) and progression-free survival (PFS) of intrahepatic cholangiocarcinoma (iCCA) after ultrasound-guided ablation and establish a model for survival risk evaluation. Data from 54 patients with 86 iCCAs between August 2008 and October 2022 were retrospectively analyzed. Cox regression were used to analyze the effects of clinical features on OS and PFS. Based on the variables screened by multivariable analysis, a model was established to predict the survival of the patients. Time-dependent receiver operating characteristic (timeROC) curve was constructed to evaluate the performance of this model. The model was further verified by bootstrap validation. The clinical usefulness of the model was evaluated by the decision curve analysis (DCA). During follow up, 39 patients died and 49 patients developed recurrence. Pre-ablation CA199 level > 140 U/ml was the only independent predictor of poor PFS. Age > 70years, early recurrence, maximal diameter of tumor size > 1.5cm and pre-ablation CA199 level > 140 U/ml were significantly associated with poor OS. Then a model was established based on the above four variables. The areas under the timeROC curve (AUC) for 1-year, 2-year, 3-year, 5-year were 0.767, 0.854, 0.791 and 0.848, respectively. After bootstrapping for 1000 repetitions, the AUCs were similar to the initial model. DCA also demonstrated thatthe model had good positive net benefits. The established model in this study could predict the survival outcomes of the patients with iCCA after thermal ablation, but further research was needed to validate the results.

Abstract B051: Genome-wide association studies of 26,187 women without ovarian cancer identifies 12 genetic loci of blood CA125

Abstract Background: CA125 is elevated in women with ovarian cancer and is the single best ovarian cancer screening biomarker candidate to date, although two randomized screening trials showed no clinically significant difference in ovarian cancer mortality. Consideration of genetic variants that influence blood CA125 levels in healthy women could improve its performance as an ovarian cancer screening biomarker. Furthermore, while studies have suggested CA125 is associated with ovarian carcinogenesis and progression, its biological role remains unclear. Thus, we aimed to identify genetic variants of CA125 in women without ovarian cancer. Methods: We conducted a genome-wide association analysis to identify common genetic variants associated with CA125 using data on 26,187 women without ovarian cancer, leveraging existing blood CA125 data and genetic data from Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), European Prospective Investigation into Cancer and Nutrition (EPIC), Nurses’ Health Studies (NHS/NHSII), and New England Case Control Study (NEC). All genotype data were inputted using TOPMed. For blood CA125 measurement, PLCO, NHS/NHSII, and NEC used the CA125II assay and EPIC used the MSD assay. We used multivariable linear regression models adjusting for age, study, and population ancestry (top 4 principal components). Analyses were conducted separately by CA125 assay, genotyping platforms, and menopausal status at blood draw. Because epidemiological predictors of CA125 differ by menopausal status, we conducted analyses stratified by menopausal status. When we meta-analyzed these results, there were no significant heterogeneity by menopausal status in majority of the genome-wide significant SNPs. Therefore, we performed a fixed-effects meta-analysis to combine summary statistics across all the results. Results: We identified 12 independent loci associated with CA125 at a genome-wide significance level (p<5 × 10−8), of which one SNP (rs73005869) had been previously linked with CA125 and is located in the MUC16 gene. In our meta-analysis, 7 SNPs were associated with lower and 5 were associated with higher levels of CA125. We discovered SNPs on chromosome 16 in the TET2 gene that were significantly associated with increased CA125 levels. We also discovered SNPs in MSLN, a gene reported to be overexpressed in ovarian tumors that contributes to metastasis in the peritoneal microenvironment, were associated with lower CA125 levels. SNPs in the HIC1 gene on chromosome 17, a tumor suppressor gene whose aberrant methylation has been observed in ovarian tumors, was associated with lower CA125 levels. Conclusion: We identified 12 independent loci associated with blood CA125 levels in women without ovarian cancer, providing novel biological insights on the role of CA125. Accounting for these genetic factors that influence blood CA125 levels could improve the performance of CA125 as ovarian cancer screening biomarker in average risk women, substantially improving survival through earlier detection of this deadly disease. Citation Format: Naoko Sasamoto, Jihye Kim, Constance Turman, Shelley S. Tworoger, Rudolf Kaaks, Renée T. Fortner, Daniel W. Cramer, Kathryn L. Terry, Nicolas Wentzensen, Peter Kraft. Genome-wide association studies of 26,187 women without ovarian cancer identifies 12 genetic loci of blood CA125 [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B051.

Abstract A050: MicroRNA as biomarkers in early detection and personalized treatment in ovarian cancer: Development of a personalized prevention consortium

Abstract Epithelial ovarian cancer (EOC) has poor survival given no effective early detection strategies and non-specific early disease symptoms. We have formed a consortium with European and American partners to provide the necessary validation of a microRNA (miRNA) panel for earlier detection of EOC using serum samples and data from prospective cohorts, paired with clinical data and biospecimens. Our objectives are to validate a serologic miRNA panel that, together with CA125, would have sufficient diagnostic discrimination to be used as a tool that, complementary to imaging, would allow early identification and direction of patients with suspected malignancy to personalized gyn-oncological care. We will validate serum miRNA profiles as biomarkers for early detection in samples collected from cases ⇐3 years prior to EOC diagnosis and matched controls and characterize sources of variation in miRNA profiles and their impact on discrimination. Evaluate miRNA profiles in the clinical setting and the discrimination between EOC cases and women with (i) benign ovarian tumors in blood samples collected prior to diagnostic surgery and (ii) underlying comorbidities (including other cancer types). Further, we will evaluate serum miRNA profiles as predictors of recurrence and will compare tumor tissue and serum miRNA profiles. Develop and optimize protocols for data integration and methods for algorithm development. Direct in silico validation, including miRNA and CA125 levels, and clinical and epidemiologic data. Address Ethical, Legal and Social Aspects (ELSA), including activities in key stakeholder groups. Challenges in health data privacy and sharing, including for development of an artificial intelligence model, will be addressed, as will the definition of a “healthy” population with respect to miRNA profiles for EOC. The consortium was launched in 2023, with the first findings expected in 2024. Beyond the initial direct aims of the consortium, expanded aims on further promising markers are envisaged. Citation Format: Renée Turzanski Fortner, Hilde Langseth. MicroRNA as biomarkers in early detection and personalized treatment in ovarian cancer: Development of a personalized prevention consortium [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A050.

Development and validation of a novel preoperative clinical model for predicting lymph node metastasis in perihilar cholangiocarcinoma

BackgroudWe aimed to develop a novel preoperative nomogram to predict lymph node metastasis (LNM) in perihilar cholangiocarcinoma (pCCA) patients.Methods160 pCCA patients were enrolled at Lihuili Hospital from July 2006 to May 2022. A novel nomogram model was established to predict LNM in pCCA patients based on the independent predictive factors selected by the multivariate logistic regression model. The precision of the nomogram model was evaluated through internal and external validation with calibration curve statistics and the concordance index (C-index). Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate and determine the clinical utility of the nomogram.ResultsMultivariate logistic regression demonstrated that age (OR = 0.963, 95% CI: 0.930–0.996, P = 0.030), CA19-9 level (> 559.8 U/mL vs. ≤559.8 U/mL: OR = 3.162, 95% CI: 1.519–6.582, P = 0.002) and tumour diameter (OR = 1.388, 95% CI: 1.083–1.778, P = 0.010) were independent predictive factors of LNM in pCCA patients. The C-index was 0.763 (95% CI: 0.667–0.860) and 0.677 (95% CI: 0.580–0.773) in training cohort and validation cohort, respectively. ROC curve analysis indicated the comparative stability and adequate discriminative ability of nomogram. The sensitivity and specificity were 0.820 and 0.652 in training cohort and 0.704 and 0.649 in validation cohort, respectively. DCA revealed that the nomogram model could augment net benefits in the prediction of LNM in pCCA patients.ConclusionsThe novel prediction model is useful for predicting LNM in pCCA patients and showed adequate discriminative ability and high predictive accuracy.

Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer

BackgroundThe role of CD161 expression on CD8+ T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161+CD8+ T cells in pancreatic ductal...

Evaluating the role of wound-healing genes in conjunction with stool routine and serum tumor markers for colorectal cancer diagnosis and prognostic implications.

Colorectal cancer is a common malignant digestive tract tumour with high morbidity and mortality. Early detection, treatment and diagnosis are crucial for preventing and treating colorectal cancer, which develops through multi-stage accumulation and gene participation, affecting tumour marker levels. Chronic wounds can lead to the development of certain cancers, such as colorectal cancer. The prolonged inflammation and tissue repair caused by chronic wounds can trigger cellular changes, potentially promoting cancerous cell growth in the colon. The formation and progression of colorectal cancer involve changes in tumour markers, such as carcinoembryonic antigen (CEA), sugar chain antigen 19-9 (CA199) and CA125. This study explores the clinical application value of a stool routine combined with serum tumour marker detection in diagnosing colorectal cancer. The experiment team examined the clinical information of 56 colorectal cancer patients alongside a control group of 56 healthy patients. Distinct stool characteristics and heightened occult blood rates were evident in colorectal cancer cases. The combined approach integrating stool routine and serum tumour markers improved diagnostic accuracy, displaying enhanced sensitivity and specificity compared with individual markers or stool routines alone. Bioinformatics analysis indicated increased CEA and CA125 levels in colorectal cancer tissues versus normal tissues, hinting at potential prognostic implications. Exploring wound-healing genes like Vascular Endothelial Growth Factor A (VEGFA), Tumour Protein 53 (TP53) and Transforming Growth Factor Alpha (TGFA) revealed heightened expression in colorectal cancer, suggesting their potential role in disease progression. These markers showed associations with various immune cell types, suggesting their impact within the tumour microenvironment (p < 0.05). Single-cell RNA sequencing data highlighted varying CEA expressions across different cell populations in colorectal cancer. The findings indicated that integrating clinical assessments with accurate biomarkers may provide valuable insights into prognostic implications.

The relationship between clinical and pathological findings and FDG - PET uptake in metastatic colorectal cancers.

In metastatic colorectal cancer (mCRC), the genetic structure and cell metabolism of the primary tumor lesion might be different from metastatic lesions. It is thought that cell-level glucose metabolism may differ due to the difference in RAS wild and mutant mCRC patients' prognosis. In this study, we aimed to compare 2-deoxy-2-[fluorine-18]-fluoro-D-glucose Positron Emission Tomography (18F-FDG PET/CT) uptake levels for KRAS mutation status and primary-metastatic tumor localization. Our study is a retrospective cohort analysis that included RAS mutation status study and staging-oriented 18F-FDG PET/CT conducted on mCRC patients. There was no significant relationship between metastasis and primary tumor maximum Standardized uptake value (SUVmax) values according to the KRAS mutational status (P > 0.05). Patients with liver metastasis along with mutant BRAF mutation status had significantly higher SUVmax values in PET-CT scans (P = 0.04). There was a negative correlation between SUVmax values of lung metastases and overall survival (r = -0.35, P = 0.04). Patients with high carcinoembryonic antigen (CEA) levels had significantly higher SUVmax values of lung metastasis than patients with normal CEA levels (P = 0.009). Patients with high CA19-9 levels had significantly higher SUVmax values of liver, peritoneal, and bone metastasis than patients with normal CA19-9 levels (P = 0.002, P = 0.001, P = 0.004, respectively). There was no significant correlation between SUVmax values of metastasis and Lactate dehydrogenase (LDH) values. Liver metastasis of right-sided mCRCs had significantly higher SUVmax values (P = 0.03). We could not demonstrate a significant association between KRAS mutation and SUVmax values of PET scan in primary or metastatic tumor sites in advanced CRC.

Reconsideration of the clinical impact of neoadjuvant therapy in resectable and borderline resectable pancreatic cancer: A dual-institution collaborative clinical study

PurposeWe investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer. MethodsA total of 687 patients with resectable or borderline resectable pancreatic cancer were enrolled. Survival analysis was performed by intention-to-treat analysis and propensity score matching (PSM) was conducted. ResultsIn resectable disease, the NAT group showed better overall survival (OS) compared with the upfront group. Multivariate analysis identified CA19-9 level (≥100 U/mL) and lymph node metastasis to be prognostic factors, and a tumor size of 25 mm was the optimal cut-off value to predict lymph node metastasis. There was no significant survival difference between patients with a tumor size ≤25 mm and CA19-9 < 100 U/mL and those in the NAT group. In borderline resectable disease, OS in the NAT group was significantly better than that in the upfront group. CEA (≥5 ng/mL) and CA19-9 (≥100 U/mL) were identified as prognostic factors; however, the OS of patients fulfilling these factors was worse than that of the NAT group. ConclusionsNAT could be unnecessary in patients with tumor size ≤25 mm and CA19-9 < 100 U/mL in resectable disease. In borderline resectable disease, surgery should be delayed until tumor marker levels are well controlled.

Cell-free DNA in plasma and ascites as a biomarker of bevacizumab response- a translational research sub-study of the REZOLVE (ANZGOG-1101) clinical trial

ObjectiveTo investigate cell-free DNA (cfDNA) in plasma and ascites and its association with clinical outcomes (paracentesis-free interval, overall survival) and CA125 level in participants with advanced ovarian cancer, treated with palliative intraperitoneal bevacizumab to delay re-accumulation of ascites. MethodscfDNA was extracted from 0.3 to 1 mL samples from 20/24 participants of the REZOLVE trial. Standard and methylation-specific PCRs were performed to measure 3 biomarkers: total cfDNA (Alu), tumour-derived cfDNA (ctDNA, methylated IFFO1 promoter) and endothelium-derived cfDNA (ec-cfDNA, unmethylated CDH5 promoter). Values were correlated to clinical outcomes. ResultscfDNA was detected in all samples, with higher yield in ascites (mean 669 ng/mL) than plasma (mean 75 ng/mL, p < 0.0001). Ascites had a higher ctDNA proportion than plasma (74 % vs. 20 %, p < 0.0001) and plasma had a higher ec-cfDNA proportion than ascites (24 % vs. 16 %, p < 0.002). High ctDNA proportion (>75 %) in ascites was associated with a significantly shorter paracentesis-free interval (median interval 47.5 versus 84 days, hazard ratio (HR) 2.21, 95 % confidence interval (CI) 0.85 to 5.73, p = 0.039) and ctDNA presence in plasma was unfavourable for survival (median survival 56 versus 242 days, HR 3.21, 95 % CI 1.15 to 9.00, p = 0.008). A significant positive correlation was observed between ctDNA proportion in plasma and CA125 level (p = 0.012). No significant difference in total cfDNA, ctDNA nor ec-cfDNA was observed between participants who were responders versus non-responders. ConclusionSufficient cfDNA was detected in both plasma and ascites to study three biomarkers. These samples can provide useful information and should be considered in the design of future ovarian cancer trials.

Study on the Diagnostic Effect of Serum Tumor Marker Detection on Benign and Malignant Pelvic Tumors

Objective: To analyze the diagnostic effect of serum tumor marker detection for benign and malignant pelvic tumors. Methods: A total of 90 subjects, including healthy individuals and patients with benign and malignant pelvic tumors, were selected for research from April 2021 to July 2022. Two milliliters of venous blood were drawn on an empty stomach in the early morning. The serum was separated and processed within 2 hours, and then microparticle chemiluminescence was used to detect various serum tumor markers, including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 125 (CA- 125), and carbohydrate antigen 19-9 (CA19-9). Results: Through testing of the observation and control groups, it was found that patients with pelvic tumors had significantly higher CA-125 and CA19-9 (P &lt; 0.05). Additionally, CA-125 and CA19-9 in patients with malignant tumors were significantly higher than those in benign patients (P &lt; 0.05). The correlation between CEA and AFP and pelvic tumor is low, while CA-125 and CA19-93 are positively correlated with the severity of the disease. Conclusion: Multiple serum tumor marker detection demonstrated a higher value for diagnosing benign and malignant pelvic tumors and can improve the sensitivity and specificity of single marker detection. Analysis of CA-125 and CA19-9 levels accurately distinguishes between benign and malignant pelvic tumors, as well as provides data support for clinical treatment.

Preoperative serum level of CA153 and a new model to predict the sub-optimal primary debulking surgery in patients with advanced epithelial ovarian cancer

ObjectiveThe aim of this study was to establish a preoperative model to predict the outcome of primary debulking surgery (PDS) for advanced ovarian cancer (AOC) patients by combing Suidan predictive model with HE4, CA125, CA153 and ROMA index.Methods76 AOC Patients in revised 2014 International Federation of Gynecology and Obstetrics (FIGO) stage III-IV who underwent PDS between 2017 and 2019 from Yunnan Cancer Hospital were included. Clinical data including the levels of preoperative serum HE4, CA125, CA153 and mid-lower abdominal CT-enhanced scan results were collected. The logistics regression analysis was performed to find factors associated with sub-optimal debulking surgery (SDS). The receiver operating characteristic curve was used to evaluate the predictive performances of selected variables in the outcome of primary debulking surgery. The predictive index value (PIV) model was constructed to predict the outcome of SDS.ResultsOptimal surgical cytoreduction was achieved in 61.84% (47/76) patients. The value for CA125, HE4, CA153, ROMA index and Suidan score was lower in optimal debulking surgery (ODS) group than SDS group. Based on the Youden index, which is widely used for evaluating the performance of predictive models, the best cutoff point for the preoperative serum HE4, CA125, CA153, ROMA index and Suidan score to distinguish SDS were 431.55 pmol/l, 2277 KU/L, 57.19 KU/L, 97.525% and 2.5, respectively. Patients with PIV≥5 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing SDS were 73.7%, 82.9%, 62.9% and 72.3%, respectively. In the constructed model, the AUC of the SDS prediction was 0.770 (95% confidence interval: 0.654-0.887), P<0.001.ConclusionPreoperative serum CA153 level is an important non-invasive predictor of primary SDS in advanced AOC, which has not been reported before. The constructed PIV model based on Suidan's predictive model plus HE4, CA125, CA153 and ROMA index can noninvasively predict SDS in AOC patients, the accuracy of this prediction model still needs to be validated in future studies.

Potential Value of HSP90α in Prognosis of Triple-Negative Breast Cancer.

BACKGROUND Triple-negative breast cancer (TNBC) is a distinct subtype of breast cancer, accounting for 12-18% of all breast cancer cases. It exhibits high heterogeneity and aggressiveness, resulting in a poorer prognosis with a high risk of early recurrence and metastasis. Due to the lack of expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2), as well as insensitivity to endocrine therapy, determining a standard treatment for TNBC is challenging. The identification of potential prognostic biomarkers is crucial for developing personalized treatment strategies for patients. MATERIAL AND METHODS Our study investigated the potential value of HSP90a in TNBC prognosis. A retrospective analysis was conducted on 127 TNBC patients and 127 Healthy controls from March 1, 2019 to July 31, 2022. Venous blood was collected and tested for HSP90alpha, CEA, CA199, and CA125, and we recorded the clinical characteristics of the patients, including age, BMI, alcohol consumption status, surgical history, CEA level, CA199 level, CA125 level, HSP90alpha level, tumor size, distant metastases, lymph node metastasis, and TNM stage. Univariate and multivariate methods were used to screen independent risk factors for progression-free survival (PFS) and overall survival (OS). RESULTS HSP90alpha is not only upregulated in TNBC but is also highly correlated with lymph node metastasis and TNM stage. The results of multivariate analysis showed that distant metastasis, TNM stage and HSP90a level were independent factors associated with PFS. BMI, tumor size, TNM stage, surgical history, and HSP90a level were independent factors influencing OS. CONCLUSIONS Our research findings demonstrate a significant association between high HSP90alpha expression and adverse clinical features, suggesting a poorer prognosis for TNBC patients.