Non-metastatic Group Research Articles

Neutrophil Lymphocyte Ratio, Platelet Lymphocyte Ratio, Systemic Inflammatory Response Index, and Systemic Immune-Inflammatory Index as Predictors of Metastasis in Renal Cell Carcinoma: A Retrospective Study

Background: The overall survival rates are below 10% in patients with metastatic renal cell carcinoma (RCC) posing a significant health challenge. There is a pressing need for novel and simple predictors of metastasis in patients with RCC to aid in early detection, thereby having prognostic and therapeutic implications. Objectives: To assess the efficacy of various inflammatory markers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), Systemic Inflammatory Response Index (SIRI), and Systemic Immune-Inflammatory Index (SII), in predicting metastasis amongst individuals diagnosed with RCC. Methods: A retrospective study was undertaken at a tertiary hospital, focusing on individuals diagnosed with RCC. Patients were divided into two groups: Those with and without metastases. Patient demographics and clinical, pathological, and laboratory data were collected. The researchers evaluated the predictive capabilities of NLR, PLR, SIRI, and SII using ROC curves, with cut-off points determined via the Youden Index. Results: Of the 91 patients, 25 (27.5%) had metastatic RCC. Significant differences in NLR (P = 0.047), PLR (P = 0.004), SIRI (P = 0.006), and SII (P = 0.005) were noted between metastatic and non-metastatic groups. The ROC analysis showed that SIRI and SII had the highest predictive capacity with areas under the curve (AUCs) of 0.687 and 0.693, respectively. Logistic regression demonstrated NLR, PLR, SII, and SIRI as independent predictors of metastasis in RCC, with a combined predictive accuracy of 83.5%. Conclusions: Neutrophil-lymphocyte ratio, PLR, SIRI, and SII are reliable predictors of metastasis in RCC, with their combined use enhancing predictive accuracy. These hematological parameters can be easily derived from routine blood tests, could help in the early diagnosis of metastases, and tailor the management of RCC, improving patient outcomes. Further multicentric studies are recommended to validate these findings and help integrate them into clinical practice.

Differential Gene Expression Analysis of The Cancer Genome Atlas Messenger Ribonucleic Acid Sequencing Data from Male Patients with and without Lymph Node Metastasis in Tongue Cancer

Gene expression plays a crucial role in progression, invasion, and metastasis in many groups of oral squamous cell carcinoma. Based on extensive patient data, no research has been done so far on the differences in gene expression between groups of male patients with tongue squamous cell carcinoma who drink alcohol and those who do not, about lymph node metastasis. Our study analysed differential gene expression in male patients with and without lymph node metastasis in tongue cancer, utilising messenger ribonucleic acid (mRNA) sequencing data from The Cancer Genome Atlas (TCGA) program. Analysis was performed using R and bioinformatics tools to process mRNA sequencing data, compare differential gene expression, and examine functional signaling pathways and survival analysis. After screening the database, 38 out of 74 cases with metastasis were selected for the analysis. The computational analysis identified a significant increase in cancer invasion transcription factors, such as GATA2, SP1 and MYC in the metastatic group, whereas CREB1 was more associated with the nonmetastatic group. Functional analysis suggested new prognostic biomarkers for unfavourable outcomes (TRIML2 and EXOSC4) and favourable outcomes (HS3ST4 and SFTPA1). New suggested markers for oral and tongue cancer such as TRIML2, EXOSC4 are known for their role in non-oral cancer including lung and liver cancer. Especially head and neck squamous cell carcinoma (HNSCC) survival analysis and protein atlas investigation confirmed the indirect biological roles of found markers. The study indicates that TRIML2 and EXOSC4 could serve as biological markers for predicting lymph node metastasis in tongue squamous cell carcinoma among male patients who consume alcohol. These findings suggest that gene expression profiles may play a role in the progression and metastasis of tongue cancer. Further research is needed to validate these results and to develop targeted therapies for patients with tongue cancer.

The lncRNA AFAP1-AS1 is upregulated in metastatic triple-negative breast tumors and controls hypoxia-activated vasculogenic mimicry and angiogenesis

BackgroundVasculogenic mimicry (VM) is an alternative intratumoral microcirculation system that depends on the capacity of tumor cells to reorganize and grow in three-dimensional (3D) channel architectures like the capillaries formed by endothelial cells. Both VM and angiogenesis may coordinately function to feed cancer cells, allowing tumor growth. Long noncoding RNAs (lncRNAs) regulate critical cellular functions in cancer cells, including cell proliferation, apoptosis, angiogenesis, invasion, and metastasis. The lncRNA, known as actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1), has been described as an oncogene in diverse types of cancers. However, its role in VM and metastasis in triple-negative breast cancer (TNBC) is unknown.MethodsReverse transcription and quantitative polymerase chain reaction (RT‒qPCR) experiments were performed to evaluate the expression of 10 selected lncRNAs from literature in metastatic and nonmetastatic biopsies from TNBC patients. The expression of AFAP1-AS1 was analyzed in Genotype-Tissue Expression Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. The AFAP1-AS1 expression was knocked in TNBC Hs578T cells by transfection of specific siRNAs. Channel-like formation assays were performed using 3D cultures over Matrigel in hypoxia-treated Hs578T cancer cells with diminished expression of AFAP1-AS1. The angiogenesis tests were conducted using human umbilical vein endothelial cells (HUVECs) and AFAP1-AS1- silenced Hs578T cells on 3D cell cultures. The presence of VM (CD31-/PAS+) in tumor tissues from TNBC patients with and without metastasis was assessed through immunohistochemistry using endothelial marker CD31 antibodies and periodic acid-Schiff (PAS) staining.ResultsCompared with normal mammary tissues, AFAP1-AS1 expression was higher in breast cancer tissues. Moreover, AFAP1-AS1 expression was upregulated in the TNBC subtype compared to receptor-positive breast tumors. In addition, the expression of AFAP1-AS1 was correlated with the expression of the thirteen genes characteristic of a previously reported hypoxia signature. Interestingly, AFAP1-AS1 was upregulated in primary TNBC tumors from patients who developed metastasis compared with the nonmetastatic group. Functional analysis revealed that the knockdown of AFAP1-AS1 in Hs578T cells significantly impaired the hypoxia-induced VM, accompanied by a decrease in the development of 3D channel networks. Similarly, AFAP1-AS1 knockdown counteracts the angiogenic potential of cancer cells, as indicated by a reduction in the number of polygons, sprouting cells, and nodes in HUVEC cells. Remarkably, an increase in CD31-/PAS + staining of 3D channel networks in primary breast tumors from metastatic patients was found compared with the nonmetastatic group. Finally, we found that the number of blood vessels increased in the nonmetastatic group more than in the metastatic cohort.ConclusionsOur data suggested that AFAP1-AS1 controls both VM and angiogenesis in Hs578T breast cancer cells and that increased metastasis is associated with VM in TNBC patients.

Is It Worth Performing Intersphincteric Resection in Patients Having Rectal Adenocarcinoma with Oligometastasis

AbstractIntersphincteric resection (ISR) is being increasingly performed in metastatic rectal adenocarcinoma (with oligometastasis) patients. There has been a trend towards worse prognosis in this group. This study compares the oncological and surgical outcomes of patients with and without pre-operative oligometastasis who underwent ISR. The outcomes compared include prognostic factors like margin positivity, recurrence rates, stoma reversal rate, and surgical failure rate (defined as a combination of one or more of the aforestated factors). The demographic pattern, American Society of Anaesthesia grade (ASA), treatment received, clinical and histopathological T and N stage, grade, type of minimally invasive surgery (MIS) approach, neoadjuvant therapy, and pathological high-risk features are also studied. Patients who underwent minimally invasive ISR over 10 years at a high-volume tertiary cancer center were selected for the study. Factors used for the assessment of oncological outcomes were margin positivity (circumferential resection and distal margin), recurrence (both local and systemic), and stoma reversal rate. A descriptive and comparative analyses were performed. Four hundred and eight patients underwent minimally invasive ISR of which 25 (6.12%) patients were oligometastatic. While R0 resection was similar in both groups, higher overall recurrence (24% versus 18.5%) and low stoma reversal rate (36.8% versus 67.3%) were observed in the oligometastatic group with statistically significant differences. No local recurrence was seen in the oligometastatic group, and the difference compared to non-metastatic group was not statistically different. This study indicates that oligometastatic patients who underwent ISR experienced lower stoma reversal rates, maintaining similar local control but facing higher rates of systemic recurrence.

Prognostic Role of Serum Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Post Stereotactic Body Radiation in Advanced Hepatocellular Carcinoma

Stereotactic body radiation therapy (SBRT) has evolved as a treatment alternative for advanced hepatocellular carcinoma (HCC) patients who are ineligible for other local therapies. Posttreatment responses are assessed by imaging modalities, serum AFP, and protein induced by vitamin K absence-II (PIVKA) II levels. Despite good specificity, both AFP and PIVKA-II have low to medium sensitivity. The study aimed to find more effective biomarkers that have an impact on the survival outcomes of the patients. We have prospectively collected blood samples from 18 patients undergoing SBRT. Serum levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor-A (VEGF-A) were analyzed kinetically pre-SBRT following day 5 and day 30 post-SBRT. Local control (LC), overall survival (OS), progression free survival (PFS), and postprocedure adverse events were recorded. The cohort had a median follow-up duration of 12.5 months (range 4-30 months). In the entire cohort, the estimated mean OS was 21.2 months (95% confidence interval [CI], 15.9-26.4), and the median progression free survival (mPFS) was 8 months (95% CI, 1.7-14.2). Patients with higher PIVKA-II levels (pre- and post-SBRT) also showed increased concentrations of VEGF-A and HGF. Patients with metastasis at presentation had higher HGF (P=0.028) and VEGF-A (P=0.027) concentrations compared to the nonmetastatic group. Patients with increased levels of VEGF-A and HGF at day 30 post-SBRT compared to day 5 had poor PFS. Indeed, the mPFS was 22 months vs 6 months (P=0.301) in patients with low VEGF-A post SBRT on day 30 compared to day 5. Similarly, mPFS in patients with increase in HGF was 6 months as compared to 22 months (P=0.326) in patients in whom HGF was reduced post-SBRT. We conclude that in addition to PIVKA-II, HGF, and VEGF-A can be used as prognostic and predictive markers for early progression of disease post-SBRT. However, further prospective trials are warranted in the future to validate the results.

Preoperative Delta Neutrophil Index, Platelet Lymphocyte Ratio and Immature Granulocyte Count for Differentiating Metastatic Colon Cancer from Non-Metastatic Colon Cancer: A Retrospective Study.

Immature granulocytes show bone marrow activation before neutrophil response and there are studies in the literature showing that the number of immature granulocytes is an auxiliary marker in the diagnosis and treatment of different diseases. The Delta Neutrophil Index (DNI), Immature Granulocyte Count (IGC) have previously been studied as markers in thyroid and breast cancers. The aim of this study was to determine whether immature granulocyte IGC and DNI values measured in preoperative blood parameters have a diagnostic benefit for the detection of advanced colon cancer. A study was conducted on patients who had undergone selective operation for colon cancer in our clinic from February 2015 to February 2020. The patients were divided into two groups: early stage (stage I-III) and advanced stage (stage IV) colon cancer. The IGC and DNI values as well as other hematological parameters, demographic parameters (sex, age) in these two groups were compared. A total of 43 patients with mean age 67.47 (35-96) years were included in the study. Eighteen of the patients were male and 25 were female. When the early stage and advanced stage colon cancer groups were compared, no statistically significant difference was found between age, sex, white blood cell count, lymphocyte-to-monocyte ratio, eosinophil count, basophil count, mean platelet volume and: systemic immune-inflammation index score. It was observed that platelet-to-lymphocyte ratio, IGC and DNI or Immature Granulocyte Percentage (IGP) values were statistically significantly higher in the metastatic colon cancer group compared to the non-metastatic group. When the specificity and sensitivity of laboratory markers in metastatic colon cancer were examined, it was observed that the specificity and sensitivity of DNI or IGP and IGC were statistically higher than other values. DNI, IGC and PLR values, which are the parameters measured in the preoperative period are easily measurable laboratory parameters and do not involve additional costs in differentiating metastatic from non-metastatic colon cancer in the preoperative period.

The value of postoperative contrast-enhanced ultrasound parameters in lymph node metastasis, tumor node metastasis, and treatment response evaluation of resected hepatocellular carcinoma.

To explore the application value of postoperative contrast-enhanced ultrasound (CEUS) parameters for lymph node metastasis (LNM), tumor, node, metastasis staging, and treatment response evaluation of resected hepatocellular carcinoma (HCC). We retrospectively analyzed 100 patients with liver cancer who underwent liver CEUS at our hospital between October 2020 and October 2022. The patient's LNM, pathological staging, and therapeutic effects were recorded based on the histopathological results. CEUS parameters were analyzed and compared CEUS parameters between different lymph node metastases, pathological stages, and therapeutic effects. Twenty-three patients experienced LNM, 77 patients did not experience LNM; and the rise time (RT), peak intensity (PI), and area under the curve (AUC) of the metastatic group were significantly smaller than those of the nonmetastatic group (P < .05). 44 cases were classified into groups I to II by pathological staging, and 56 cases were classified into groups III to IV. The RT, PI, and AUC of groups III to IV were significantly lower than those of groups I-II (P < .05). Seventy-nine cases were complete necrosis, 21 cases were residual or recurrent; The RT, PI, and AUC of the residual or recurrent group were significantly lower than those of the complete necrosis group (P < .05). The receiver operating characteristic curve shows that RT, PI, and AUC have a certain value in evaluating LNM, pathological staging, and treatment response of HCC, and the combined evaluation/evaluation value of these 3 factors is relatively high. The postoperative CEUS parameters RT, PI, and AUC can be used for LNM, pathological staging evaluation, and treatment response evaluation of HCC. Moreover, the combination of the 3 parameters is feasible and valuable in evaluating LNM, tumor, node, metastasis staging, and treatment response of HCC.

Genetic analysis of metastatic versus nonmetastatic conjunctival melanoma using a cutaneous melanoma gene expression panel

ObjectiveConjunctival melanoma (CJM) is a rare subtype of mucosal melanomas. Despite an increasing understanding of CJM genetics, predicting patient prognosis remains challenging. Here we sought to see if a 31-gene expression profile (31-GEP) test (i.e., DecisionDx-Melanoma) originally developed and validated for cutaneous melanoma (CM) could be useful in the prognostication of patients with CJM. Design/ParticipantsWe performed a single-center retrospective review and gene expression profiling of 10 patients with CJM. MethodsDeidentified archived samples of each primary tumor were sent to Castle Biosciences, where 31-GEP testing was performed. Patients were followed until death or a minimum of 5 years postexcision and monitored for tumor recurrence or metastatic spread. Mean fold change in individual gene expression was compared between nonmetastatic and metastatic groups via independent t-tests. ResultsFifty percent of patients developed metastatic disease and had reduced overall survival (3.6 vs 9.3 months; p = 0.018). In 4 of 10 patients, two nonmetastatic and two metastatic, tumor samples passed Castle Biosciences quality control allowing for class designation. All metastatic patients and one nonmetastatic patient were designated as class 2B. The final nonmetastatic patient was designated as class 1B. In individual gene analysis, BAP1 expression was significantly reduced in the metastatic group (p = 0.03). ConclusionsIn assessing if a CM gene expression panel could aid in the risk stratification of patients with CJM, we found that the uveal melanoma-relevant gene, BAP1, may be important. Additional studies with larger sample sizes are needed to determine the relevance of this and other differentially expressed genes in CJM prognostication.

Short-term mortality among very elderly cancer patients in the intensive care unit: A retrospective cohort study based on the Medical Information Mart for Intensive Care IV database.

The objective of this study is to examine the epidemiological characteristics of very elderly patients (aged over 80 years) with cancer admitted to the intensive care unit (ICU), and to elucidate the association between Acute Physiology Score III (APS-III) and 28-day mortality. A retrospective analysis was conducted using data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients aged 80 years and above were assigned to three groups: non-cancer group, non-metastatic cancer group, and metastatic cancer group, based on their cancer diagnosis and its extent, Kaplan-Meier curves were constructed among these patient groups. Furthermore, patients were divided into a survival group and a non-survival group based on their 28-day survival status after ICU admission. Univariate and multivariate logistic regression analyses were performed to detect the risk factors for 28-day mortality among these patients. Additionally, this investigation sought to establish a dose-response relationship by exploring the graded association between APS-III scores and the 28-day mortalities among patients diagnosed with cancer. A total of 42,037 medical records were screened, from which 11,461 elderly patients aged over 80 years were included, comprising 1020 (8.90%) with non-metastatic cancer, 537 (4.68%) with metastatic cancer, and 9904 (86.41%) without cancer. Significant differences in 28-day mortality were observed between both the non-metastatic and metastatic cancer groups compared to the non-cancer group (20.98% and 22.35% vs. 15.75%, p < 0.001). However, no statistically significant difference was detected in the 28-day mortality rate when comparing the non-metastatic cancer group directly with the metastatic cancer group (20.98% vs. 22.35%, p = 0.576). Univariate analysis revealed significant differences (p < 0.001) in age, gender, BMI, aCCI excluding cancer point, ventilation, presence of cancer, and status of metastatic cancer between the survival and non-survival groups. In the multivariate logistic regression, the odds ratio (OR) for ventilation was found to be 2.154 (95% CI: 1.799-2.578), cancer conferred an OR of 1.499 (95% CI: 1.137-1.975), metastatic cancer showed an OR of 1.171 (95% CI: 0.745-1.841), APS-III showed an OR of 1.038 (95% CI: 1.034-1.042). A dose-response relationship was observed, demonstrating that when the APS-III score exceeded 80 points, the 28-day mortality rate surpassed 50% among the very elderly cancer patients in ICU. More than one-tenth of critically ill very elderly patients admitted to the ICU are diagnosed with cancer. Among ICU patients, those with cancer face a short-term mortality risk approximately 1.5 times higher than those without a cancer diagnosis. Interestingly, while our findings do not indicate an escalated mortality risk due to metastasis within the cancer patient cohort, the presence of cancer itself remains a significant factor influencing ICU mortality rates in this very elderly population.

Assessment of the Clinicopathologic Characteristics and Survival Rates of Colorectal Cancer Among Syrian Refugees and Turkish Population in Gaziantep Province.

Syrian refugees (SRs) have had difficulties in the diagnosis, treatment, and follow-up of chronic diseases, such as cancer, because of the conflict in the region. The cancer diagnosis and treatment process of SR are also a matter of curiosity. We aimed to compare the demographic characteristics and survival outcome data of SRs and Turkish citizens (TCs), and colorectal cancer (CRC) is one of the most common cancer types seen with similar frequency globally. A total of 421 patients with CRC were included. Overall survival (OS) was estimated using the Kaplan-Meier method, and the log-rank test was used for comparison. Patient demographic data were compared using the Pearson Chi-square test and independent t test. In total, 421 patients (282 TCs and 139 SRs) were included in this study. The mean age was 52.9 ± 14.3 years for the entire population: 55.3 ± 14.1 years for TCs and 47.9 ± 13.4 years for SRs. Forty (29%) SRs and 60 (21.4%) TCs had de novo metastatic disease (P = .08). The median OS in the general population was 57.9 months (95% CI, 40.1 to 75.7), whereas it was 80.9 months (95% CI, 56.5 to 97.2) in TCs and 42.2 months in SRs (95% CI, 27.0 to 57.4; P = .006). In the nonmetastatic group, the median OS did not reach (NR) in TCs, and it was 52.6 months (95% CI, 43.7 to 61.5) in SRs (P = .02). In the metastatic group, the median OS was 21 months (95% CI, 8.5 to 29.2) in TCs, and it was 18.9 months in SRs (95% CI, 16.3 to 25.7; P = .93). The survival rate was lower in the SR group. Since CRC is also common among refugees, developing and implementing methods to improve the welfare of vulnerable populations is necessary.

Exploring Mitochondrial Autophagy Dysregulation in Osteosarcoma: Its Implications for Prognosis and Targeted Therapy

Objective: This study aimed to investigate the differential expression of mitophagyrelated genes in osteosarcoma patients with distinct prognostic outcomes and explore potential molecular regulatory mechanisms. Methods: We analyzed microarray data from metastatic and nonmetastatic osteosarcoma patients using the UCSC dataset. Differential gene screening and intersection of mitophagy-related genes were performed using NetworkAnalyst. Random forest and LASSO regression were employed to screen selected genes and establish a risk prediction model. Functional enrichment analysis, protein- protein interaction (PPI) networks, immunoassays, and in vitro experiments were conducted to validate the findings. Results: Seven differentially expressed genes were identified, and a robust risk prediction model was developed (AUC=0.886). PPI and functional enrichment analyses provided insights into relevant molecules and regulatory pathways. The immunoassay results revealed differences in the immune environment between the metastatic and nonmetastatic groups. Immunohistochemistry demonstrated significant downregulation of EPHA3 expression in the metastatic group, and in vitro experiments indicated that inhibiting EPHA3 increased the proliferative activity and migration ability of osteosarcoma cells. Conclusion: Our study suggests that the downregulation of EPHA3 may contribute to mitochondrial autophagy dysfunction, thereby increasing the risk of osteosarcoma metastasis.

Value of perfusion characteristics evaluated by CEUS combined with STQ parameters in diagnosing the properties of SLN in breast cancer.

Accurate sentinel lymph node (SLN) characterization is essential for breast cancer management, prompting advancements in imaging technologies such as contrast-enhanced ultrasound (CEUS) and sound touch quantification (STQ) to enhance diagnostic precision. To explore the value of perfusion characteristics evaluated by CEUS combined with STQ parameters in diagnosing the properties of sentinel lymph node (SLN) in breast cancer. A total of 91 breast cancer patients (91 SLNs) admitted to the hospital from February 2022 to December 2023 were selected for this study. Among them, 26 patients with metastatic SLN confirmed by surgery and pathology were included in the metastatic SLN group, and 65 patients with non-metastatic SLN were included in the non-metastatic SLN group. Preoperative examination results of CEUS and STQ were retrospectively analyzed. The diagnostic efficacy of perfusion characteristics evaluated by CEUS and STQ parameters for the properties of SLN in breast cancer was analyzed using the receiver operating characteristics (ROC) curve. Statistical methods such as chi-square tests and logistic regression analysis were employed to analyze the data. Enhancement patterns differed significantly between the metastatic SLN and non-metastatic SLN groups (p< 0.05). ROC curve analysis indicated that CEUS perfusion characteristics had an AUC value of 0.823 for diagnosing SLN properties, with a sensitivity of 84.62% and specificity of 70.77% using type I as the critical value. Additionally, STQ measurement showed significantly higher values in the metastatic SLN group (44.18 ± 6.53 kPa) compared to the non-metastatic SLN group (34.69 ± 6.81 kPa) (t= 6.075, p< 0.001). The AUC value for STQ parameters in diagnosing metastatic SLN was 0.849, with a sensitivity of 73.08% and specificity of 92.31% using 42.40 kPa as the critical value. Though the AUC value of STQ measurement was higher than CEUS perfusion characteristics alone, the difference was not statistically significant (Z= 0.393, p= 0.695). Moreover, combining CEUS perfusion characteristics with STQ parameters yielded an AUC value of 0.815 for diagnosing SLN properties, showing no significant difference compared to diagnosis with CEUS or STQ parameters alone (Z= 0.149, 0.516, p= 0.882, 0.606). Combined use of perfusion characteristics evaluated by CEUS and STQ parameters can significantly improve the diagnostic specificity of SLN in breast cancer. It is worthy of clinical promotion.

Quantitative analysis of peri-intestinal lymph node metastasis using indocyanine green fluorescence imaging technology.

We evaluated the efficacy of indocyanine green fluorescence imaging compared to that of traditional nanocarbon dyes in assessing peri-intestinal lymph node metastasis in patients with colorectal cancer, which is a key prognostic factor. The relationship between indocyanine green fluorescence imaging and histopathological outcomes in patients with colon cancer has also been explored. A retrospective analysis was conducted on 30 patients with colon cancer (from May to October 2023) confirmed by surgical pathology. Tumors were marked with indocyanine green (ICG) or nanocarbon via colonoscopy 16 to 24 hours before surgery. Within 15 minutes after surgery, peri-intestinal lymph node fluorescence imaging and hematoxylin and eosin staining were used to assess the distribution of cancer foci. The correlation between cancer foci distribution, fluorescence intensity, and area under the receiver operating characteristic curve was measured. Among 243 metastatic lymph nodes from 30 patients, 18 were found. After the patients were divided into metastatic and nonmetastatic groups, significant differences in tumor differentiation and stage were noted (P < .001). The fluorescence intensity was strongly correlated with the presence and proportion of metastasis (area under the receiver operating characteristic curve = 0.931), whereas nanocarbon staining showed no significant correlation (P = .81). All P values were two-sided, with P < .05 indicating statistical significance. Lymph nodes with malignant intestinal tumor metastasis displayed weaker ICG fluorescence than did nonmetastatic nodes. Combining ICG and nanocarbon staining techniques enhances intraoperative lymph node dissection and postoperative analysis, indicating their potential utility in colorectal cancer surgery.

The value of net influx constant based on FDG PET/CT dynamic imaging in the differential diagnosis of metastatic from non-metastatic lymph nodes in lung cancer.

This study aims to evaluate the value of the dynamic and static quantitative metabolic parameters derived from 18F-fluorodeoxyglucose (FDG)-positron emission tomography/CT (PET/CT) in the differential diagnosis of metastatic from non-metastatic lymph nodes (LNs) in lung cancer and to validate them based on the results of a previous study. One hundred and twenty-one patients with lung nodules or masses detected on chest CT scan underwent 18F-FDG PET/CT dynamic + static imaging with informed consent. A retrospective collection of 126 LNs in 37 patients with lung cancer was pathologically confirmed. Static image analysis parameters include LN-SUVmax and LN-SUVmax/primary tumor SUVmax (LN-SUVmax/PT-SUVmax). Dynamic metabolic parameters including the net influx rate (Ki) and the surrogate of perfusion (K1) and of each LN were obtained by applying the irreversible two-tissue compartment model using in-house Matlab software. Ki/K1 was then calculated as a separate marker. Based on the pathological findings, we divided into a metastatic group and a non-metastatic group. The χ2 test was used to evaluate the agreement of the individual and combined diagnosis of each metabolic parameter with the gold standard. The receiver-operating characteristic (ROC) analysis was performed for each parameter to determine the diagnostic efficacy in differentiating non-metastatic from metastatic LNs with high FDG-avid. P < 0.05 was considered statistically significant. Among the 126 FDG-avid LNs confirmed by pathology, 70 LNs were metastatic, and 56 LNs were non-metastatic. For ROC analysis, in separate assays, the dynamic metabolic parameter Ki [sensitivity (SEN) of 84.30%, specificity (SPE) of 94.60%, accuracy of 88.89%, and AUC of 0.895] had a better diagnostic value than the static metabolic parameter SUVmax (SEN of 82.90%, SPE of 62.50%, accuracy of 74.60%, and AUC of 0.727) in differentiating between metastatic from non-metastatic LNs groups, respectively. In the combined diagnosis group, the combined SUVmax + Ki diagnosis had a better diagnostic value in the differential diagnosis of metastatic from non-metastatic LNs, with SEN, SPE, accuracy, and AUC of 84.3%, 94.6%, 88.89%, and 0.907, respectively. When the cutoff value of Ki was 0.022ml/g/min, it had a high diagnostic value in the differential diagnosis between metastasis and non-metastasis in FDG-avid LNs of lung cancer, especially in improving the specificity. The combination of SUVmax and Ki is expected to be a reliable metabolic parameter for N-staging of lung cancer.

MUC16 as a serum-based prognostic indicator of prometastatic gastric cancer

Metastatic gastric cancer (GC) presents significant clinical challenges due to its poor prognosis and limited treatment options. To address this, we conducted a targeted protein biomarker discovery study to identify markers predictive of metastasis in advanced GC (AGC). Serum samples from 176 AGC patients (T stage 3 or higher) were analyzed using the Olink Proteomics Target panels. Patients were retrospectively categorized into nonmetastatic, metastatic, and recurrence groups, and differential protein expression was assessed. Machine learning and gene set enrichment analysis (GSEA) methods were applied to discover biomarkers and predict prognosis. Four proteins (MUC16, CAIX, 5’-NT, and CD8A) were significantly elevated in metastatic GC patients compared to the control group. Additionally, GSEA indicated that the response to interleukin-4 and hypoxia-related pathways were enriched in metastatic patients. Random forest classification and decision-tree modeling showed that MUC16 could be a predictive marker for metastasis in GC patients. Additionally, ELISA validation confirmed elevated MUC16 levels in metastatic patients. Notably, high MUC16 levels were independently associated with metastatic progression in T3 or higher GC. These findings suggest the potential of MUC16 as a clinically relevant biomarker for identifying GC patients at high risk of metastasis.

Comparison of the diagnostic efficacy of systemic inflammatory indicators in the early diagnosis of ovarian cancer.

This study aimed to determine the diagnostic accuracy of CA125, HE4, systemic immune-inflammation index (SII), prognostic nutritional index (PNI), fibrinogen-to-albumin ratio (FAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the combination of the six inflammatory-nutritional markers for ovarian cancer (OC) to identify the best diagnostic indicator for OC early diagnosis. An extensive study was performed to establish the connection between these indicators and the pathological aspects of OC. A total of 170 individuals were included in this study, with 87 diagnosed with OC and 83 with benign ovarian tumors (BOTs). The diagnostic abilities of the variables were evaluated by calculating sensitivity, specificity, and area under the ROC curves. Through the use of DCA, we evaluated the variables' clinical value in the discrimination of ovarian masses. All markers showed significant diagnostic power for OC. CA125, HE4, SII, FAR, and MLR levels significantly increased from the BOTs group to the early-stage OC group. The advanced-stage OC group had significantly lower PNI values compared to the early-stage OC group but significantly higher levels of CA125, HE4, SII, NLR, and FAR. Moreover, the OC group with lymph node metastasis exhibited significantly higher levels of CA125, HE4, SII, NLR, PLR, and FAR, in contrast to the non-metastatic group, while PNI levels were significantly lower. Categorical factors, such as histological grade and pathological classification, showed noticeable discrepancies in CA125 and HE4 levels. NLR was significantly different among the pathological type groups. Among the six inflammatory-nutritional markers, the FAR displayed the greatest diagnostic value. In the analysis of logistic regression, it was observed that a combination marker containing all six inflammatory-nutritional markers exhibited a notably higher AUC value (0.881; 95% CI, 0.823 - 0.926) than any of the individual marker. PNI, NLR, PLR, MLR, SII, and FAR showed excellent diagnostic performance for OC. The combination of these markers demonstrated a superior diagnostic capability compared to each individual one. The systemic inflammatory indicators may be helpful to diagnose OC.

Novel candidate metastasis-associated genes for synovial sarcoma.

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with poor prognosis due to late recurrence and metastasis. Metastasis is an important prognostic factor of SS. This study aimed to identify the core genes and mechanisms associated with SS metastasis. Microarray data for GSE40021 and GSE40018 were obtained from the Gene Expression Omnibus database. 186 differentially expressed genes (DEGs) were identified. The biological functions and signalling pathways closely associated with SS metastasis included extracellular matrix (ECM) organization and ECM-receptor interaction. Gene set enrichment analysis showed that the terms cell cycle, DNA replication, homologous recombination and mismatch repair were significantly enriched in the metastasis group. Weighted gene co-expression network analysis identified the most relevant module and 133 hub genes, and 31 crossover genes were identified by combining DEGs. Subsequently, four characteristic genes, EXO1, NCAPG, POLQ and UHRF1, were identified as potential biomarkers associated with SS metastasis using the least absolute shrinkage and selection operator algorithm and validation dataset verification analysis. Immunohistochemistry results from our cohort of 49 patients revealed visible differences in the expression of characteristic genes between the non-metastatic and metastatic groups. Survival analysis indicated that high expression of characteristic genes predicted poor prognosis. Our data revealed that primary SS samples from patients who developed metastasis showed activated homologous recombination and mismatch repair compared to samples from patients without metastasis. Furthermore, EXO1, NCAPG, POLQ and UHRF1 were identified as potential candidate metastasis-associated genes. This study provides further research insights and helps explore the mechanisms of SS metastasis.

LINC00665 promotes the progression and immune evasion of lung cancer by facilitating the translation of TCF7 protein through dependence on IRES

ObjectiveTo investigate the influence of LINC00665 on the development and immune evasion of lung cancer.MethodsTumor tissues and corresponding adjacent tissues were collected from 84 lung cancer patients, categorized into non-metastatic (n = 58) and metastatic (n = 26) groups. LINC00665 expression in lung cancer and metastatic lung cancer tissues was assessed via qRT-PCR. Pearson correlation analysis was conducted to examine the correlation between LINC00665 and immune-modulating cytokines (TGF-β, IL-10, IL-1β, IFN-γ, IL-2, TNF-α). A549 and H1299 cells, with relatively high LINC00665 expression, were used for in vitro studies. Cells were transfected with LINC00665-targeting shRNA, and changes in proliferation, apoptosis, migration, invasion, and NK cell cytotoxicity were assessed. Downstream molecular mechanisms of LINC00665 were investigated using GEO database analysis, highlighting the association with HHLA2. LINC00665’s role in promoting HHLA2 expression via binding with TCF7 was explored. In low LINC00665-expressing A549/H1299 cells, overexpression of HHLA2 was performed to evaluate effects on malignant behavior and NK cell sensitivity. A xenograft model was established for in vivo validation through tumor volume and weight measurements, Ki-67 immunoreactivity analysis, and flow cytometry analysis of CD107a + NK cells.ResultsLINC00665, TCF7 mRNA, and HHLA2 mRNA expression levels were significantly higher in lung cancer tissues than adjacent tissues, with non-metastatic lung cancer showing higher expression than metastatic lung cancer. In metastatic lung cancer, LINC00665 positively correlated with immune-suppressive cytokines (TGF-β, IL-10, IL-1β) and negatively correlated with anti-tumor cytokines (IFN-γ, IL-2, TNF-α). LINC00665 knockdown significantly inhibited lung cancer cell growth and metastasis, promoting sensitivity to NK cells. Further analysis revealed that LINC00665 recruits transcription factor TCF7 to upregulate HHLA2 expression in lung cancer cells, thereby facilitating lung cancer development and immune escape.ConclusionLINC00665, through recruitment of TCF7 and upregulation of HHLA2, inhibits NK cell cytotoxicity, promoting the development and immune evasion of lung cancer.

System analysis based on Anoikis-related genes identifies MAPK1 as a novel therapy target for osteosarcoma with neoadjuvant chemotherapy

BackgroundOsteosarcoma (OS) is the most common bone malignant tumor in children, and its prognosis is often poor. Anoikis is a unique mode of cell death.However, the effects of Anoikis in OS remain unexplored.MethodDifferential analysis of Anoikis-related genes was performed based on the metastatic and non-metastatic groups. Then LASSO logistic regression and SVM-RFE algorithms were applied to screen out the characteristic genes. Later, Univariate and multivariate Cox regression was conducted to identify prognostic genes and further develop the Anoikis-based risk score. In addition, correlation analysis was performed to analyze the relationship between tumor microenvironment, drug sensitivity, and prognostic models.ResultsWe established novel Anoikis-related subgroups and developed a prognostic model based on three Anoikis-related genes (MAPK1, MYC, and EDIL3). The survival and ROC analysis results showed that the prognostic model was reliable. Besides, the results of single-cell sequencing analysis suggested that the three prognostic genes were closely related to immune cell infiltration. Subsequently, aberrant expression of two prognostic genes was identified in osteosarcoma cells. Nilotinib can promote the apoptosis of osteosarcoma cells and down-regulate the expression of MAPK1.ConclusionsWe developed a novel Anoikis-related risk score model, which can assist clinicians in evaluating the prognosis of osteosarcoma patients in clinical practice. Analysis of the tumor immune microenvironment and chemotherapeutic drug sensitivity can provide necessary insights into subsequent mechanisms. MAPK1 may be a valuable therapeutic target for neoadjuvant chemotherapy in osteosarcoma.

Treating lung cancer in resource limited setting: Retrospective study from Armenia.

e20055 Background: Lung cancer (LC) is second most common cancer by incidence in Armenia. Every year approximately 800-900 new cases are diagnosed, from all cases 55.5% are in the 4th stage. Methods: We have collected data from three oncology centers in Armenia: Yeolyan Hematology and Oncology Center, Mikaelyan Institute of Surgery, and Muratsan Hospital Complex of Yerevan State Medical University. In this retrospective hospital-based study the data of patients with LC who were treated at these three centers during the 01 Oct 2009 - 31 Dec 2023 period was collected․ Results: Four hundred and eighty-nine LC patients were involved in the final analysis. Male to female ratio was 6:1. From the all patients 10.6% were diagnosed at age ≤ 50, 79,6% of patients 50-70, and 9.6% ≥ 70 years. In 71.6% of all cases, LC was diagnosed in current or former smokers. Only 3% of patients were diagnosed in stage I, 9.8% in stage II, 44.8% in stage III, 41.1% in stage IV, and for 1.2% of patients' stage was unknown. From all cases 74% of patients had non small cell lung cancer (NSCLC), 22.7% small cell lung cancer (SCLC) and 3.3% had other histological types of lung cancer. Of all patients 63% are dead. The median overall survival (mOS) for all stages was 21 months for the entire cohort. Median OS was not reached for stage I ( &gt; 100 months), was 61 months for stage II, 23 months for stage III, and 13 months for stage IV (p &lt; 0,001). ALK mutation was checked in 22.7%, EGFR in 22%,ROS in 14.1%, KRAS in 11.2%, BRAF in 9.8% and of all patients. From all checked AKL was positive in 1.8%, EGFR in 19.4%, ROS in 2.8%, KRAS in 21.8%, BRAF in 8,3% and of cases. For patients with stage IV lung cancer (41.1%), we found a significant difference in mOS in those who received first line immunotherapy in combination with chemotherapy (19,4%) compared to those who received only chemotherapy (74.1%) (mOS: 24 months vs 11 months accordingly, p = 0.014). For stage I-III LC patients, those who received systematic therapy with cisplatin showed better overall survival than those who received systemic therapy with carboplatin (mOS 31 vs 25 months, p = 0.01), but for stage IV LC patients survival difference was not found (mOS 15 vs 12 months, p = 0.24). Conclusions: In Armenia, lung cancer is mostly diagnosed in the advanced stage where overall survival is approximately one year. In our study population, those who received immunotherapy in combination with chemotherapy showed doubled mOS, compared with only chemotherapy. In the nonmetastatic group, chemotherapy with cisplatin showed a significant increase in mOS compared with carboplatin.