Clinicopathological Characteristics Of Patients Research Articles

Analysis of TERT mRNA Levels and Clinicopathological Features in Patients with Peritoneal Mesothelioma

Background/Objectives: Telomerase reverse transcriptase (TERT) is the catalytic subunit of the telomerase enzyme responsible for telomere length maintenance and is an important cancer hallmark. Our study aimed to clarify the mRNA expression of TERT in peritoneal mesothelioma (PeM), and to explore the relationship between its expression and the clinicopathological parameters and prognosis of patients with PeM. Methods: In a cohort of 13 MpeM patients, we evaluated histotype, nuclear grade, mitotic count, necrosis, inflammation, Ki67, BAP1, MTAP and p16 expression by immunohistochemistry, p16/CDKN2A status by FISH and TERT mRNA expression by RNAscope. Results: Our results showed several statistical correlations between TERT mRNA-score and other investigated features: (i) a poor positive correlation with BAP1 score (r = 0.06340; p ≤ 0.0001); (ii) a moderate positive correlation with p16 FISH del homo (r = 0.6340; p ≤ 0.0001); (iii) a fair negative correlation with p16 FISH del hetero (r = −0.3965; p ≤ 0.0001); a negative poor correlation with MTAP (r = −0.2443; p ≤ 0.0001); and (iv) a negative fair correlation with inflammatory infiltrate (r = −0.5407; p = 0.0233). Moreover, patients survive for a significantly longer time if they have a low mitotic index adjusted (2–4 mitotic figures per 2 mm2) (p ≤ 0.0001), are male (p = 0.0152), lose BAP1 (p = 0.0152), are p16 positive and present no deletion or heterozygous for p16 (p ≤ 0.01). Conclusions: TERT is highly expressed in PeM, but it is not one of the crucial factors in evaluating the prognosis of patients. Nevertheless, the results validate the prognostic significance of the mitotic index, BAP1 loss and p16/CDKN2A status.

Investigating the association of VHL gene variants with disease risk and clinicopathological outcomes in ccRCC patients from West Bengal, India.

Clear cell renal cell carcinoma (ccRCC) is a prevalent and aggressive malignancy, with the von Hippel-Lindau (VHL) gene playing a critical role in its pathogenesis. However, the association between VHL gene variants and sporadic ccRCC risk remains unexplored in the Indian population. This study aimed to investigate the somatic and germline variants of the VHL gene in sporadic ccRCC patients from West Bengal, India, and their association with disease risk and clinicopathological parameters. A total of 210 ccRCC patients and 255 ethnicity-matched healthy controls were enrolled. Genomic DNA from blood and tissue samples was analyzed using PCR-based Sanger sequencing. The association of VHL variants with ccRCC risk was assessed using Chi-square tests. The impact of genetic variants on patient clinicopathological features and overall survival was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. We identified twenty-three single nucleotide variants (SNVs) in the VHL gene, including 3 novel variants, OR250433 T > G, OR125589 C > T and OQ627404 G > C. The intronic variant rs61758376 G > C and 3'UTR variant rs1642742 A > G were significantly associated with an increased risk of ccRCC (OR = 1.676, P = 0.0074; OR = 1.735, P = 0.0171, respectively). The rs1642742 GG genotype was also significantly associated with larger tumor size (P < 0.05) and advanced tumor stage (pT4). Kaplan-Meier analysis indicated poorer overall survival for patients with the rs1642742 GG genotype (log-rank P = 0.029). Our study is the first to document the association of VHL gene variants with sporadic ccRCC risk and clinical outcomes in the Indian population. The identified variants, particularly rs61758376 and rs1642742, could serve as potential biomarkers for ccRCC susceptibility and prognosis.

Pleural metastases from differentiated thyroid cancer: clinical features and long-term outcomes.

Pleural metastasis (PM) is rare in patients with differentiated thyroid cancer (DTC). Radioiodine (131I) therapy has been the main treatment for postoperative metastasis and recurrence of DTC. However, clinical data on PM from DTC are limited. This study investigated the clinicopathological characteristics of patients with PM from DTC that was treated surgically and with 131I therapy and evaluated their long-term prognosis and prognostic factors. Review of the Shanghai Sixth People's Hospital medical records for 2010-2023 identified PM in 27 of 14,473 patients with DTC. Overall survival (OS) was assessed by the Kaplan-Meier method. The prevalence of PM in DTC was 1.87‰ (27/14,473). The median age at the time of initial diagnosis of PM was 59 years (range 34-79). At the end of follow-up, eight patients (29.63%) had disease progression (PD), four (14.81%) had partial response (PR), and the remainder had stable disease (SD); no patient achieved complete response (CR). Twelve patients (44.44%) died and 15 (55.56%) survived. Thirteen patients (48.15%) did not show 131I avidity, and 16 (59.26%) had radioiodine-refractory DTC (RR-DTC). Twenty patients (74.07%) had malignant pleural effusion (MPE), which was large in 11 cases (40.74%), moderate in two. More than moderate MPE (P=0.031), lack of 131I avidity (P=0.041), and RR-DTC (P=0.030) were significantly associated with worse 5-year OS in patients with PM of DTC. PM is rare in DTC. Lack of 131I avidity, RR-DTC, and more than moderate MPE are associated with a poor OS in patients with DTC and PM.

Appendiceal Neuroendocrine Tumor: Clinicopathologic Characteristics of Six Cases and Review of the Literature.

Appendiceal neuroendocrine tumors (ANETs) are the most prevalent type of appendiceal neoplasm and the fifth most common neuroendocrine tumor in the gastrointestinal tract. In this study, we described the clinicopathological features of patients with ANET. We reviewed the clinicopathological findings and histopathological reports of six patients diagnosed with ANET between January 2014 and December 2023 at Korea University Medical Center, Anam Hospital. Six cases, comprising three males and three females, were diagnosed during procedures for lower abdominal pain or other medical reasons. Most tumors were less than 1 cm in size and located at the tip of the appendix. One patient had a large tumor (4.1 cm) with lymph node metastasis. Four tumors extended to the muscularis propria, whereas two infiltrated the subserosal soft tissue. The tumor cells exhibited a typical trabecular and nested pattern with monotonous round or oval nuclei. All patients had a mitotic count of less than 2 per 10 high-power fields and a Ki-67 labeling index of less than 1%, classifying them as having G1 well-differentiated tumors. Immunohistochemical staining showed that all cases were positive for CD56 and synaptophysin, and four were positive for chromogranin A. No recurrence or distant metastasis was observed during follow-up. ANETs are relatively uncommon and mostly benign in terms of prognosis. Because of their malignant potential, meticulous examination of appendectomy specimens is warranted to identify the presence of ANETs.

Efficacy and Safety of Three Cycles of TIP and Sequential High Dose Chemotherapy in Patients with Testicular Non-Seminomatous Germ Cell Tumors

Background: Salvage treatment options have not been validated in relapsed or refractory germ cell tumors. Moreover, the study populations including these patients have different heterogeneities. This study aimed to evaluate the efficacy and safety of three cycles of TIP sequential high-dose chemotherapy in patients with testicular non-seminomatous germ cell tumors who relapsed or had a refractory course after first-line platinum-based chemotherapy. Methods: Data of 141 patients who underwent three cycles of TIP followed by HDCT due to relapsed/refractory gonadal NSGCTs after first-line cisplatin-based chemotherapy (BEP/EP) at Gulhane School of Medicine Hospital Medical Oncology Department between January 2017 and May 2024 were evaluated retrospectively. Patients underwent a treatment regimen consisting of two phases. Initially, they received three cycles of induction therapy using a combination known as TIP, which includes paclitaxel, ifosfomide, and cisplatin. Following this, they were given a single cycle of high-dose chemotherapy. Demographic and clinicopathological features of patients and treatment-related complications and survival outcomes were recorded. Results: Median follow-up for all patients was 35.2 (95% CI, 29.45 to 41.07) months. Complete Response (CR) or marker negative Partial Response (PR) after HDCT was achieved in 84 (59.6%) patients. Median time for PFS not reached (NR) (95% CI, NR) in the entire group. The 2-year PFS rate was 51.8%. Median time for OS not reached (95% CI, NR) and the 2-year OS rate was 72.3%. The most common myelotoxicity observed after HDCT until engraftment was grade 4 neutropenia (100%) and grade 4 thrombocytopenia (96.5%). Transplantation-related mortality occurred in 7.1% of patients. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis for overall survival were platinum refractory disease and AFP and/or beta HCG elevation. Conclusions: Significant survival can be achieved after three cycles of TIP consecutive HDCT, while treatment-related mortality was found to be low.

Palbociclib in real clinical practice: Results of a single-center observational study

Introduction. A breakthrough in the treatment of metastatic hormone-dependent (HR+) breast cancer was combination endocrine therapy with CDK4/6 inhibitors, which significantly prolonged the tumor response time to treatment and the median survival before progression. The effectiveness of combination endocrine therapy in real-life practice is of particular interest due to the wider population of patients with different somatic status and comorbidity, often not included in randomized trials.Aim. Analyze of palbociclib using for treating patients with HR+/HER2– advanced breast cancer (mBC) at the Republican Clinical Oncology Dispensary.Materials and methods. Data from 323 patients were analyzed. Our study examined the effectiveness of combination endocrine therapy with palbociclib in patients with metastatic HR+ HER2– breast cancer. Data on the clinicopathological characteristics of patients and disease progression during palbociclib administration were obtained by reviewing clinical data from patient records and radiological/pathological examination reports.Results. The median age of patients included in the study was 62 years. When assessing the antitumor response, a partial response was recorded in 54 patients (16.7%), stabilization in 212 patients (65.6%), and progression in 57 patients (17.8%). The median progression-free survival was 13 months. Grade 3 adverse events were noted in 23 patients: neutropenia in 21.7% of cases, hepatotoxicity in 47.8% of cases, cardiotoxicity in 17.4% of cases, and coagulopathy in 4.3%. No patient discontinued therapy due to adverse events. The best treatment results were achieved by patients who used the combination of palbociclib with an endocrine partner as the first line of treatment for advanced stage.Conclusion. This analysis of real-world data on the use of palbociclib in real-world clinical practice confirms the RCT data on the efficacy and safety of using CDK4/6 inhibitors for the treatment of patients with HR+ HER2- mBC.

Prognostic and clinicopathological role of pretreatment systemic inflammation response index (SIRI) in gastric cancer: a systematic review and meta-analysis

BackgroundThe systemic inflammatory response index (SIRI) is calculated via the following formula: SIRI = monocyte count × neutrophil count/lymphocyte count. The value of the SIRI in predicting the prognosis of gastric cancer (GC) remains controversial. This study revealed the precise effect of the SIRI in predicting GC prognosis through a meta-analysis.MethodsThe ability of the SIRI to predict GC prognosis was evaluated by calculating combined hazard ratios (HRs) and 95% confidence intervals (CIs). Furthermore, the combined odds ratios (ORs) and 95% CIs were determined to analyze the associations between the SIRI and the clinicopathological characteristics of patients with GC.ResultsSeven publications on a total of 1763 cases were included in this study. The SIRI threshold was between 0.58 and 1.35, and the median value was 0.85. Our pooled findings revealed that a higher SIRI was significantly linked with poor overall survival (OS) (HR = 1.87, 95% CI = 1.59–2.20, p < 0.001) and disease-free survival (DFS; HR = 1.88, 95% CI = 1.50–2.36, p < 0.001) in GC patients. However, the SIRI did not exhibit a significant association with sex (OR = 1.98, 95% CI = 0.82–4.75, p = 0.126), surgery type (OR = 0.96, 95% CI = 0.61–1.51, p = 0.847), tumor differentiation (OR = 0.75, 95% CI = 0.54–1.06, p = 0.099), or TNM stage (OR = 1.25, 95% CI = 0.34–4.62, p = 0.743) in patients with GC.ConclusionsAn elevated SIRI was significantly associated with unfavorable OS and DFS in patients with GC. Thus, the SIRI is a reliable biomarker for predicting GC prognosis in clinical practice.

The prognostic value of vascular endothelial growth factor in endometrial cancer: A protocol for systematic review and meta-analysis.

A large number of studies have shown that high expression of vascular endothelial growth factor (VEGF) in cancer tissues is associated with poor prognosis of various cancers. However, this finding in endometrial cancer is controversial. Therefore, this meta-analysis aimed to explore the effects of VEGF on survival in patients with endometrial cancer. Four databases of PubMed, Medline, Web of Science, and China National Knowledge Infrastructure were searched to collect literature that met the inclusion criteria. The association between high VEGF expression and survival outcomes and clinicopathological features of patients with cancer was evaluated by calculating the combined hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI). The Begg test was used to assess publication bias. A total of 11 studies were included, involving 1251 patients. The results showed that compared with low VEGF expression, high VEGF expression was significantly associated with shorter overall survival (HR = 2.44, 95% CI = 1.15-5.16, I2 = 80%, P = .02) and disease-specific survival (HR = 7.87, 95% CI = 1.70-36.44, I2 = 64%, P = .008) but not with disease-free survival (HR = 1.45, 95% CI = 0.70-3.02, I2 = 68%, P = .32). In addition, VEGF expression is higher in patients with advanced stage (OR = 3.70, 95% CI = 2.22-6.19, P < .001), lower histological differentiation (OR = 2.08, 95% CI = 1.22-3.55, P = .007), and lymph node metastasis (OR = 5.42, 95% CI = 2.35-5.11, P < .001). High VEGF expression can predict poor prognosis and poor clinicopathological features in patients with endometrial cancer, and it may be a valuable new indicator to evaluate the prognosis of patients with endometrial cancer.

Impact of telomere length for risk assessment and prognosis in papillary thyroid cancer depending on the clinicopathological features.

. Despite the establishment of a link between telomere status and carcinogenesis, lack of a consensus in the cancer specific pattern of telomere length has a severe impact on the use of relative telomere length (RTL) in cancer diagnosis. The disparity in assessing the relationship between telomere length and cancer risk is complex and may vary as it is influenced by other factors. The objective of this study is to thoroughly examine the intricate relationship between telomere length and cancer incidence in Papillary Thyroid Cancer (PTC) depending on the tumor type, stage, patients' sex and age. Therefore, the current study is focused on the association of RTL in PTC patients with different clinicopathological characteristics and compared with controls to determine the risk of PTC and expected survival time after surgery. . This study included 126 patients with PTC and 80 controls. RTL in thyroid tissues was measured using quantitative (q) PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. Kaplan-Meier and Cox regression were used to analyze postsurgical outcomes. . The RTL of patients was significantly shorter than that of controls. A short RTL was significantly correlated with an elevated risk of PTC in patients aged ≥ 55 years, female sex, classic subtype, and tumor size > 2cm. A short RTL did not affect the overall survival of patients with PTC; however, it was associated with poor survival in patients with tumor size > 2cm and tumor invasion. . This unique study combines the use of RTL with various clinicopathological features of patients with PTC. In conclusion, RTL is a promising tumor marker that correlates with the clinical characteristics of patients with PTC. Specifically, RTL < 0.6 could be used with age, sex, tumor size > 2cm and tumor invasion to predict the risk of PTC development and prognosis of the disease. This study will open new horizon in the use of molecular marker such as RTL for understanding its association with increased cancer risk in patients with different clinicopathological features.

Efficacy of neoadjuvant PD-1/PD-L1 inhibitor in resectable NSCLC: a meta-analysis based on randomized controlled trials

BackgroundThe efficacy of neoadjuvant immunotherapy in resectable non-small-cell lung cancer (NSCLC) is controversial. The aim of this study is to explore the efficacy of additional PD-1/PD-L1 inhibitors in the neoadjuvant treatment of resctable NSCLC.MethodsData sources included Cochrane Library, Embase, Web of Science, and PubMed from beginning of the database creation to May 2024. The primary outcomes of the study included event-free survival (EFS), overall survival (OS), pathological complete response (pCR), major pathological response (MPR).ResultsSeven RCTs, including 2929 patients, were included in the analysis. The results showed that the experimental group had significantly higher rates of pCR (RR = 5.9, p < 0.001) and MPR (RR = 2.88, p < 0.001) compared to the control group. OS (HR = 0.57) and EFS (HR = 0.58) was also significantly improved in the experimental group. Subgroup analysis of EFS revealed that the benefit was higher in the East (HR = 0.56) than in the West (HR = 0.70). Additionally, the benefit seemed to rise with PD-L1 tumor cell proportion score (TPS) (TPS < 1%, HR = 0.76; 1% < TPS < 49%, HR = 0.56; TPS ≥ 50%, HR = 0.38). The benefit degree seemed to be higher in the III period patients (HR = 0.75) than I-II period patients (HR = 0.52). It is important to emphasize that smokers (HR = 0.54, p < 0.001) benefited from neoadjuvant immunotherapy but nonsmokers (HR = 0.68, p = 0.055) did not.ConclusionNeoadjuvant PD-1/PD-L1 inhibitor combined with chemotherapy can significantly improve the short-term and long-term prognosis of patients with resectable NSCLC. Moreover, the efficacy of this treatment regimen may be affected by different clinicopathological characteristics of patients.

Prognostic significance of programmed death ligand 2 expression in tumor-infiltrating lymphocytes of triple-negative breast cancer

Objectives: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and overexpression of human epidermal growth factor receptor 2 protein. Patients with high expression of programmed death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) have been found to have better prognosis and increased response to anti-PD-1/PDL1 immunotherapy. However, the role programmed death ligand 2 (PD-L2), the other known ligand of PD-1, plays in PD-1/PD-L1 checkpoint pathway has not been well studied. Therefore, this project aims to investigate (1) the relationship between PD-L2 expression in tumor infiltrating lymphocytes (TILs) and patient clinicopathological features, (2) whether PD-L2 can serve as a predictor of patient survival, and (3) the association of PD-L2 expression with the infiltration of relevant immune cell types in the tumor microenvironment. Materials and Methods: Two hundred and ninety-six (296) TNBC cases diagnosed between 2003 and 2013 in Singapore General Hospital were used in this study to create tissue microarray for immunohistochemistry with several antibodies. Results: Patients with PD-L2 expression were found to have significantly improved disease-free survival (hazard ratio [HR] 0.51; P = 0.0362) and overall survival (HR 0.43; P = 0.0379) compared to patients who have negative PD-L2 expression. PD-L2+ TILs correlate significantly with CD3+ T-cells (P = 0.00776) and CD20+ B-cells (P = 0.001019) infiltration in the stromal compartments and intratumoral CD38+ plasma cells (P = 0.048869) infiltration. Conclusion: Like PD-L1, PD-L2 positivity in TILs was found in our study to indicate a better prognosis compared to PD-L2-negative patients.

New prognostic index for neoadjuvant chemotherapy outcome in patients with advanced high-grade serous ovarian cancer

BackgroundA validated prognostic index for the outcome of patients with advanced high-grade serous ovarian cancer (HGSOC) undergoing neoadjuvant chemotherapy (NACT) remains elusive. To address this need, we developed an ovarian neoadjuvant chemotherapy prognostic index (ONCPI) to improve predictive accuracy.MethodsWe encompassed an analysis of the clinicopathological characteristics of patients with advanced HGSOC who were administered platinum-based NACT. Blood inflammatory composite markers were calculated and converted into binary values using optimal cutoffs. Omental hematoxylin and eosin (H&E) stained slides were selected for the assessment of chemotherapy response score (CRS), which served as a measure of NACT efficacy. Logistic regression analysis and Cox proportional hazards regression model were utilized to construct a prognostic index.ResultsMultivariate logistic analysis showed that both CRS and neutrophil-to-lymphocyte ratio (NLR) independently influenced the response to platinum-based chemotherapy. Meanwhile, Kaplan–Meier and Cox regression analysis revealed that CRS score was significantly correlated with progression-free survival (PFS) and overall survival (OS), and patients with high NLR showed poor OS. We further developed an ovarian neoadjuvant chemotherapy prognostic index (ONCPI) based on the CRS and NLR. The area under the curve (AUC) value of ONCPI was 0.771 (P < 0.001, 95% CI: 0.656–0.887) for the prediction of platinum resistance. This AUC value surpasses that of the individual NLR and CRS, which were 0.670 (P = 0.018, 95% CI: 0.547–0.793) and 0.714 (P = 0.003, 95% CI: 0.590–0.839), respectively. Moreover, survival analysis suggested that patients with ONCPI of 0 and 1 were significantly associated with improved PFS and OS.ConclusionsThe ONCPI emerges as a significant prognostic marker for predicting NACT outcome in advanced HGSOC patients and holds promise for integration into clinical practice and risk-stratified trial design.

Prognostic prediction models for postoperative patients with stage I to III colorectal cancer based on machine learning.

Colorectal cancer (CRC) is characterized by high heterogeneity, aggressiveness, and high morbidity and mortality rates. With machine learning (ML) algorithms, patient, tumor, and treatment features can be used to develop and validate models for predicting survival. In addition, important variables can be screened and different applications can be provided that could serve as vital references when making clinical decisions and potentially improving patient outcomes in clinical settings. To construct prognostic prediction models and screen important variables for patients with stage I to III CRC. More than 1000 postoperative CRC patients were grouped according to survival time (with cutoff values of 3 years and 5 years) and assigned to training and testing cohorts (7:3). For each 3-category survival time, predictions were made by 4 ML algorithms (all-variable and important variable-only datasets), each of which was validated via 5-fold cross-validation and bootstrap validation. Important variables were screened with multivariable regression methods. Model performance was evaluated and compared before and after variable screening with the area under the curve (AUC). SHapley Additive exPlanations (SHAP) further demonstrated the impact of important variables on model decision-making. Nomograms were constructed for practical model application. Our ML models performed well; the model performance before and after important parameter identification was consistent, and variable screening was effective. The highest pre- and postscreening model AUCs 95% confidence intervals in the testing set were 0.87 (0.81-0.92) and 0.89 (0.84-0.93) for overall survival, 0.75 (0.69-0.82) and 0.73 (0.64-0.81) for disease-free survival, 0.95 (0.88-1.00) and 0.88 (0.75-0.97) for recurrence-free survival, and 0.76 (0.47-0.95) and 0.80 (0.53-0.94) for distant metastasis-free survival. Repeated cross-validation and bootstrap validation were performed in both the training and testing datasets. The SHAP values of the important variables were consistent with the clinicopathological characteristics of patients with tumors. The nomograms were created. We constructed a comprehensive, high-accuracy, important variable-based ML architecture for predicting the 3-category survival times. This architecture could serve as a vital reference for managing CRC patients.

Expressions of SHOX2, RASSF1A and PTGER4, and the relationship between their methylation and clinicopathological characteristics in patients with lung cancer

Background: To explore the expressions of short stature homobox2 (SHOX2), Ras-association domain family 1A (RASSF1A) and prostaglandin E receptor 4 (PTGER4), and the relationship between their methylation and clinicopathological characteristics in patients with lung cancer (LC). Methods: The surgical specimens of cancer tissues and para-carcinoma tissues were collected from 50 patients with LC in the Affiliated Hospital of Hebei University of Engineering between January and November 2023. The expressions of SHOX, RASSF1A and PTGER4 proteins in cancer tissues and para-carcinoma tissues were detected by immunohistochemistry, and methylation status of SHOX, RASSF1A and PTGER4 genes in peripheral venous blood was detected by sulfite-modified real-time fluorescence quantification. The positive expression rates of SHOX2, RASSF1A and PTGER4, and positive rates of SHOX2, RASSF1A and PTGER4 genes methylation in cancer tissues and para-carcinoma tissues were compared. The relationship between SHOX2, RASSF1A, PTGER4 methylation and clinicopathological characteristics in LC patients was compared by real-time fluorescence quantitative PCR. Results: The positive expression rates of SHOX2, RASSF1A and PTGER4 in cancer tissues were 44.0%, 54.00% and 50.00%, significantly lower than those in para-carcinoma tissues (90.00%, 96.00%, 82.00%, P&lt;0.05). The methylation positive rates of SHOX2, RASSF1A and PTGER4 genes in cancer tissues were 48.00%, 32.00% and 64.00%, significantly higher than those in para-carcinoma tissues (16.00%, 4.0%, 14.00%, P&lt;0.05). In terms of different pathological types and TNM staging, methylation positive rates of SHOX2 and RASSF1A genes were the highest in patients with adenocarcinoma and TNM staging at stage IV. In terms of different pathological types, methylation positive rate of PTGER4 gene was the highest in patients with TNM staging at stage IV (P&lt;0.05). Conclusion: The low expressions and high methylation of SHOX2, RASSF1A and PTGER4 are common in LC patients. The methylation positive rates of SHOX2 and RASSF1A genes are related to pathological types and TNM staging, and methylation positive rate of PTGER4 gene is only related to pathological types.

Serum pentraxin-3 as a potential biomarker for diagnosis and prognosis in primary liver cancer: An observational study.

This study aimed to examine serum pentraxin 3 levels in patients with primary liver cancer and to assess its potential as a diagnostic and prognostic biomarker. Serum samples were obtained from 180 patients with primary liver cancer and 180 healthy control subjects. The concentration of PTX3 in these samples was measured using an ELISA kit. The study also investigated the correlation between PTX3 levels and the clinicopathological characteristics of patients with primary liver cancer. The effectiveness of serum PTX3 in diagnosing primary liver cancer was evaluated using receiver operating characteristic (ROC) curves and their corresponding areas under the curve (AUC). The prognostic significance of serum PTX3 in patients with primary liver cancer was assessed using Kaplan-Meier survival curves. Serum PTX3 levels were elevated in patients with primary liver cancer compared to those in healthy control subjects. These levels were significantly correlated with drinking history, TNM stage, BCLC stage, tumor size, tumor number, and vascular invasion. However, no significant correlations were observed between PTX3 levels and other factors, such as age, sex, BMI, liver cirrhosis, histological grade, and histological type. With a cut-off value of 5.1 ng/mL, PTX3 effectively differentiated patients with primary liver cancer from healthy control subjects, achieving an AUC of 0.734, a sensitivity of 73.24%, and a specificity of 84.78%. Patients with higher serum PTX3 levels had lower overall survival rates and recurrence-free survival rates than those with lower PTX3 levels. Serum PTX3 levels are elevated in patients with primary liver cancer and high serum PTX3 levels are associated with poor prognosis. This suggests that serum PTX3 has the potential to be a novel biomarker for both the diagnosis and prognosis of primary liver cancer. These findings may improve patient outcomes by enabling early detection and continuous monitoring.

Diagnostic Value of Joint Detection of Serum TK1, TSGF, CA199, and CA724 for Gastric Cancer and Its Relationship With Clinicopathologic Features and Prognosis.

To assess the diagnostic value of joint detection of serum TK1, TSGF, CA199, and CA724 for gastric cancer and its relationship with clinicopathologic features and prognosis. The 105 gastric cancer patients were enrolled. The diagnostic value of serum TK1, TSGF, CA199, and CA724 for gastric cancer and the relationship between these indicators and the clinicopathologic characteristics of gastric cancer patients were evaluated. During the follow-up period, recurrence, metastasis, and death were considered as poor prognosis. The relationships between serum TK1, TSGF, CA199, and CA724 levels and poor prognosis and factors affecting the poor prognosis of gastric cancer patients were analyzed. TK1, TSGF, CA199, and CA724 levels in the gastric cancer group were higher; serum TK1, TSGF, CA199, and CA724 levels were higher in gastric cancer patients with tumor diameters ≥3cm, TNM stages III and IV, low/moderate degree of differentiation, infiltration depths of the muscular or plasma layer, and lymphatic metastases; AUC of combined TK1, TSGF, CA199, and CA724 (0.894) was higher than that of the four indicators alone; the percentage of gastric cancer patients with poor prognosis in patients with low serum TK1, TSGF, CA199, and CA724 levels was lower; serum TK1, TSGF, CA199, and CA724 levels were factors influencing poor prognosis of gastric cancer patients (all P < 0.05). Elevated serum levels of TK1, TSGF, CA199, and CA724 are associated with clinicopathologic features and poor prognosis of gastric cancer and may be used as serum biomarkers for prognostic evaluation of gastric cancer patients.

Clinicopathological characteristics of Japanese patients with breast cancer and MET exon 14 skipping alterations.

In non-small cell lung cancer, alterations in mesenchymal-epithelial transition (MET) have been recognized as novel therapeutic targets. In particular, the MET exon 14 skipping mutation (METex14s) is a rare oncogenic driver. Targeted therapy with MET tyrosine kinase inhibitors has recently been approved for this mutation. However, c-MET expression and METex14s frequency and their clinicopathological effects in Japanese patients with breast cancer (BC) remain unknown. Tissue microarray-based immunohistochemistry (IHC) was performed to measure c-MET expression in 930 patients with BC (808 with invasive and 122 with noninvasive BC). Reverse transcription polymerase chain reaction was performed to analyse METex14s in patients exhibiting c-MET expression. Clinicopathological characteristics, including patient prognosis based on c-MET expression and METex14s, were elucidated. IHC staining revealed c-MET expression in 91/930 (9.7%) patients. Notably, IHC expression was frequently observed in apocrine carcinomas (11/26 cases). Among the c-MET IHC-positive cases, METex14s frequency was 25.9% (14/54 cases) in invasive BC and 54.1% (20/37 cases) in noninvasive BC. Furthermore, 4/11 informative noninvasive and invasive BC cases with apocrine differentiation carried METex14s. The nuclear grade was significantly higher in the METex14s-positive group among invasive BC with c-met IHC expression. Furthermore, patients' age and negative rate for PgR IHC was significantly lower in the METex14s-positive group among noninvasive BC. Regarding the factors associated with patient outcomes, both c-MET IHC staining and METex14s expression did not affect survival, regardless of the hormone receptor status. High c-MET expression and METex14s are common in apocrine carcinoma.

Cardiovascular autonomic neuropathy in chronic kidney disease: a study of kidney biopsy cases

BackgroundThe interplay between cardiac and kidney functions is mediated by the autonomic nervous system. Cardiovascular autonomic neuropathy (CAN) is a well-documented dysfunction of this system, with heart rate variability (HRV) serving as the principal diagnostic tool. CAN is recognized as a prognostic marker for adverse kidney outcomes in diabetic kidney disease (DKD). However, the pathogenesis of CAN in patients with nondiabetic chronic kidney disease (CKD) remains underexplored. This study elucidated the prevalence of CAN and its clinicopathologic characteristics in patients with nondiabetic CKD.MethodsThis cross-sectional analysis evaluated 165 nondiabetic CKD patients who underwent kidney biopsy from 2020 to 2023. HRV was quantified using the coefficient of variation of the RR interval (CVRR). CAN was diagnosed based on the CVRR and defined using the CVRR reference value—derived by defining the age and sex-dependent lower normal limits as the 2.5 percentile point of the distribution of the CVRR values in healthy individuals.ResultsThe median patient age was 47.0 (34.0–57.0) years, and 50.9% were male. The median estimated glomerular filtration rate was 65.0 (42.0–85.0) mL/min/1.73m2, and the CVRR was 3.5 (2.4–4.7)% and 16 patients (9.7%) were diagnosed with CAN. CAN was frequently associated with kidney dysfunction, dyslipidemia, and advanced interstitial fibrosis/tubular atrophy (IF/TA). Multivariable analysis revealed that IF/TA was associated with CVRR, independent of established risk factors for CAN (P = 0.045).ConclusionsThe prevalence of CAN diagnosed using the CVRR in this nondiabetic CKD cohort was 9.7%, which is four times higher than that in healthy individuals. Nondiabetic CKD patients with CAN was associated with advanced IF/TA.

Investigating the Pathogenicity of Uncommon KRAS Mutations and Their Association with Clinicopathologic Characteristics in Patients with Colorectal Cancer.

Kirsten rat sarcoma viral oncogene homolog (KRAS) somatic mutations occur in 30% to 40% of patients with colorectal cancer (CRC). These were thought to equally affect prognosis and resistance to anti-epidermal growth factor receptor agents; however, recent data show the activity of KRAS-G12C and pan-RAS inhibitors. The effects of uncommon KRAS (uKRAS) variants are largely unexplored. The distribution and pathogenicity of uKRAS mutations and their relationship with patients' clinicopathologic features were assessed. A total of 2427 CRCs were profiled for KRAS using next-generation sequencing (NGS). The study and control groups included patients with uKRAS (<1% frequency in CRC data sets on cBioPortal) and canonical KRAS mutations, respectively. In silico protein structure modifications and prediction analyses were performed by using PyMOL, trRosetta, and PolyPhen-2. uKRAS mutations affected 35 cases (1.5%), with G13C (28.6%), G12R (20%), and V14I (8.6%) being most common. Missense mutations (D33E, G12W, G12F, Q22H, Q61L, and L19F) occurred in nine cases (25.7%). Duplications (G10dup and L52_G60dup) affected two cases. Pathogenicity analyses showed that G12W, Q22R, L56V, and A130I mutations are probably damaging, with scores between 0.928 and 1.000. No differences were seen in clinicopathologic features. uKRAS mutants had lower event-free survival but no difference in overall survival compared with controls. Although these data are hypothesis generating and need further confirmation, they highlight the importance of NGS-based profiling to identify CRC patients with uKRAS mutations as candidates for personalized therapy.

Identification of ETV5 as a prognostic marker related to epigenetic modification in pan-cancer and facilitates tumor progression in hepatocellular carcinoma

ETS variant transcription factor 5 (ETV5), a master transcription factor during development, exerts vital function on the occurrence and progression of various cancers. In order to systematically analyze and explore ETV5 potential specific regulatory mechanisms in pan-cancer, RNA sequencing data and clinicopathological features of patients with various tumors were obtained through the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, and an integrated data mining analysis was carried out, including the association of ETV5 expression with patient prognosis, drug sensitivity and epigenetic modification. The results revealed that abnormally highly expressed ETV5 resulted in unfavorable prognosis and differential drug sensitivity in multiple malignancies, and its expression was associated with epigenetic modification modulators including EZH2. ETV5 related genes were enriched in tumorigenesis biological processes and signaling pathways. In hepatocellular carcinoma, ETV5 expression was correlated with patients’ tumor pathological stage and resulted in adverse outcome of patients. Our further experiments evidences indicated that ETV5 facilitated cell proliferation and reduced sensitivity to GSK126 via regulating EZH2. Collectively, this study comprehensively elucidates the carcinogenic effects and molecular mechanisms of ETV5 in tumorigenesis and development, and provides theoretical basis and guidance for tumor diagnosis, targeted therapy for ETV5 and clinical epigenetic drug research.