International Journal of Biological Markers最新文献

Purpose: As a usual malignant tumor in urinary system, renal cell cancer is regulated by microRNAs (miRNAs). This study revealed the prognostic value and regulatory effect of miR-190a-5p in renal cell cancer patients.

Methods: A total of 253 renal cell cancer patients were included for prognostic value analysis. The target gene of miR-190a-5p was detected by luciferase reporter assay. Cell Counting Kit-8 analysis and Transwell analysis were performed to explore the proliferation, removal capability, and invasiveness of 786-0 and A498 cells. Prognostic value was calculated by Kaplan-Meier curve and Cox regression analysis.

Results: miR-190a-5p was more down-regulated in tumor tissues than in adjacent tissues. Renal cell cancer cases were differed as low and high groups ground on mean miR-190a-5p expression in tumor tissues. Overall survival probability was obviously high in patients with high miR-190a-5p level (log-rank test P = 0.011). Cox regression analysis revealed that miR-190a-5p expression (relative risk (RR) = 1.751, 95% confidence interval (CI) = 1.057-2.900, P = 0.030) and tumor node metastasis stage (RR = 1.719, 95% CI = 1.059-2.792, P = 0.028) were specialty indicators for poor renal cell cancer prognosis. GDF11 was directly targeting miR-190a-5p. Overexpressed miR-190a-5p could reduce the GDF11 expression, proliferation, removal capability, and invasiveness of renal cell cancer 786-0 and A498 cells. Elevated GDF11 could lead to a changeover of proliferation, removal capability, and invasiveness inhibition, which is induced by miR-190a-5p.

Conclusion: miR-190a-5p was reduced in renal cell cancer tissues, and predicted worse outcomes of renal cell cancer cases. Overexpressed miR-190a-5p could restrain the proliferation, removal capability, and invasiveness of renal cell cancer cells via suppressing GDF11.

Introduction: In ovarian cancer, expression of metabolism-related markers has been investigated in several studies focusing on individual markers; however, a parallel quantitative evaluation of markers mapping to distinct metabolic processes and their prognostic value in large patient cohorts is still lacking.

Methods: Here, by using immunohistochemistry followed by digital pathology, we investigated the expression of several markers related to glycolysis including monocarboxylate transporter 1 and 4 (MCT1, MCT4), glutamine metabolism (glutaminase, GLS) and hypoxia/acidosis (carbonic anhydrase 9, CA IX) in tissue microarrays of > 300 patients recruited in the MITO16A clinical trial, which involved treatment of ovarian cancer patients with carboplatin/taxol plus bevacizumab.

Results: Regarding the prognostic impact of these markers, results indicate that GLS expression correlated with progression-free survival, but this effect disappeared when data were corrected for multiple testing. All other markers showed no correlation with clinical outcome.

Conclusion: These results indicate marked heterogeneity of expression of metabolism-associated markers in ovarian cancer; however, there was a lack of association with clinical benefit after chemotherapy/anti-vascular endothelial growth factor treatment. Notwithstanding the lack of prognostic value, knowledge of the pattern of expression of these biomarkers in tumors can be useful for patient stratification purposes when new drugs targeting these metabolic pathways will be tested.

Introduction: Breast cancer is a disease with high global prevalence. Clinical inflammatory biomarkers have been proposed as prognostic indicators in oncology. This research aims to determine the relationship between inflammatory markers and overall survival in breast cancer patients from four representative hospitals in Lima, Peru.

Methods: This is a multicentric, analytical, longitudinal retrospective cohort study with survival analysis in female patients with breast cancer, from 2015 to 2020, who had received at least one complete treatment regimen. The dependent variable was overall survival, and the independent variables were inflammatory markers neutrophil lymphocyte ratio, platelet lymphocyte ratio (PLR), albumin, and red cell distribution width; intervening variables included age, clinical stage, molecular subtype, and other known prognostic factors. The Kaplan-Meier method was applied to generate survival curves with the Log-Rank test, and finally, Cox regression, to find crude and adjusted hazard ratios (HR).

Results: Of 705 evaluated patients, 618 were analyzed. The mean age was 56.6 ± 12.3 years, 18.0% of patients were pure HER2 positive, 39.3% luminal A, 29.9% luminal B, 11.0% triple-negative, and 81.4% showed overweight and obesity. The average overall survival was 51.1 months. In the multivariate analysis, factors significantly related to lower overall survival were PLR > 150 (adjusted HR: 2.33; 95% confidence interval (CI): 1.22, 4.44) and stage III (adjusted HR: 4.15; 95% CI: 1.35, 12.83).

Conclusions: The Elevated Platelet-Lymphocyte Index and advanced clinical stage were associated with lower overall survival in breast cancer patients. Furthermore, PLR >150 proved to be an independent prognostic factor for mortality.

Background: Non-muscle invasive bladder cancer (NMIBC) is the most prevalent type of bladder cancer, typically associated with a favorable prognosis and a risk of recurrence during the follow-up period. Inflammatory markers have been used to predict prognosis in various cancer types. The aim of this study was to explore the prognostic value of the readily accessible inflammatory markers, platelet-to-lymphocyte ratio (PLR) and interleukin-6 (IL-6), in NMIBC.

Methods: The study comprised a retrospective analysis of clinical data collected from NMIBC patients diagnosed between October 2018 and October 2020. PLR was calculated using the routine preoperative blood test results, and preoperative IL-6 levels were recorded. Receiver operating characteristic (ROC) curves were generated for PLR and IL-6 level and the optimal cut-off values were determined using Youden's index. Survival curves were generated to evaluate the association between PLR and IL-6, and recurrence-free survival (RFS), and univariate and multivariate analysis were performed using the Cox proportional hazards regression model. A nomogram and calibration curve were generated to assess the clinical significance of the model.

Results: The ROC curves demonstrated that PLR and IL-6 levels were significantly associated with tumor pathology grade, with area under the curve (AUC) values of 0.833 (95% CI 0.757, 0.910) for PLR and 0.724 (95% CI 0.622, 0.825) for IL-6 levels. PLR and IL-6 levels were also positively associated with tumor recurrence, with AUC values of 0.647 (95% CI 0.538, 0.756) and 0.846 (95% CI 0.769, 0.924), respectively. The survival curves indicated that patients with high PLR and high IL-6 levels had shorter RFS than those with low PLR and low IL-6 level (P < 0.01). Univariate Cox proportional hazards regression analysis showed that age, tumor size, tumor number, pathological grade, PLR and IL-6 were potential risk factors for NMIBC recurrence. Multivariate analysis further revealed that tumor number, smoking, PLR, and IL-6 were independent risk factors for NMIBC recurrence (P < 0.05).

Conclusions: Preoperative peripheral blood inflammatory markers (PLR and IL-6) are useful predictors of RFS in NMIBC patients at the time of initial diagnosis. High PLR and high IL-6 were identified as independent risk factors for tumor recurrence and could serve as potential biological markers for prediction of NMIBC recurrence.

Purpose: Gastric cancer is the most common malignancy worldwide and is the third leading cause of cancer-related deaths, urgently requiring an early and non-invasive diagnosis. Circulating extracellular vesicles may emerge as promising biomarkers for the rapid diagnosis in a non-invasive manner.

Methods: Using high-throughput small RNA sequencing, we profiled the small RNA population of serum-derived extracellular vesicles from healthy controls and gastric cancer patients. Differentially expressed microRNAs (miRNAs) were randomly selected and validated by reverse transcription-quantitative real-time polymerase chain reaction. Receiver operating characteristic curves were employed to assess the predictive value of miRNAs for gastric cancer.

Results: In this study, 193 differentially expressed miRNAs were identified, of which 152 were upregulated and 41 were significantly downregulated. Among the differently expressed miRNA, the expression levels of miR-21-5p, miR-26a-5p, and miR-27a-3p were significantly elevated in serum-derived extracellular vesicles of gastric cancer patients. The miR-21-5p and miR-27a-3p were closely correlated with the tumor size. Moreover, the expression levels of serum miR-21-5p and miR-26a-5p were significantly decreased in gastric cancer patients after surgery.

Conclusions: The present study discovered the potential of serum miR-21-5p and miR-26a-5p as promising candidates for the diagnostic and prognostic markers of gastric cancer.

Background: Long non-coding RNAs (lncRNAs) in serum were useful and promising biomarkers for diagnostic and prognostic application. Herein, we investigated the serum lncRNA LINC00339 expression and its role in nasopharyngeal carcinoma.

Methods: In this study, we recruited a cohort of 129 nasopharyngeal carcinoma patients, 68 patients with nasopharyngitis, and 80 healthy controls. Serum LINC00339 levels were measured by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic (ROC) and Kaplan-Meier curve analyses were conducted to evaluate th e clinical role of LINC00339. The effects of linc00339 on cellular activities were measured using CCK-8 and Transwell assays.

Results: We observed that serum LINC00339 expression was upregulated in nasopharyngeal carcinoma patients and closely associated with tumor node metastasis stage, lymph node metastasis, and overall survival rate. Meanwhile, ROC analysis showed serum LINC00339 had diagnostic value to distinguish nasopharyngeal carcinoma patients from healthy individuals and nasopharyngitis patients. Silencing of LINC00339 could repress cellular behaviors by targeting miR-152.

Conclusion: This study clarified that LINC00339 was upregulated in nasopharyngeal carcinoma, and that serum LINC00339 may act as a diagnostic or prognostic marker, and a hopeful therapeutic target for patients with nasopharyngeal carcinoma.

Background: Cervical cancer is the most prevalent malignant tumor in women. This study aims to detect collagen type V α1 chain (COL5A1) expression and its clinical relevance in the prognosis of patients with cervical cancer.

Methods: Cervical cancer tissues and their paired adjacent normal tissues were prepared for tissue microarray. The expression of COL5A1 protein and the scores of the expression were evaluated by immunohistochemistry (IHC) staining. The prognostic value of COL5A1 was analyzed by R software version 4.2.1 with "survival, survminer, ggplot2" packages and Gene Expression Profiling Interactive Analysis (GEPIA). The cBioPortal database was utilized for the analysis of COL5A1 gene mutations.

Results: COL5A1 protein was overexpressed in human cervical cancer tissues compared to their paired adjacent normal tissues detected by IHC (P < 0.001). High expression of COL5A1 tends to be in elderly patients with cervical cancer. Survival analyses of clinical data of patients with cervical cancer showed that a high level of COL5A1 expression was significantly correlated with shorter overall survival (P = 0.031) and disease-free survival (P = 0.042) of patients. Further analyses of The Cancer Genome Atlas-Cervical Squamous Cell Carcinoma and the GEPIA survival datasets confirmed the association of high COL5A1 expression with poor overall survival of patients (P = 0.040 and P = 0.018, respectively). The analysis of genomic alterations of COL5A1 using the cBioPortal tool revealed that the COL5A1 gene was altered in 4% of cervical cancer patients and COL5A1 corresponding protein alterations with post-translational modifications were hydroxylation.

Conclusion: COL5A1 is a tissue biomarker correlated with the poor prognosis of patients with cervical cancer, which may lead to a new clinical application.

Background: Several studies show that the long non-coding RNA HOX transcript antisense RNA (HOTAIR) was upregulated in human cancer, which was associated with several clinical features and may have the potential to be prognostic markers. However, the significance of HOTAIR in hepatocellular carcinoma remains unclear. We performed a meta-analysis and bioanalysis to further investigate the association between HOTAIR and hepatocellular carcinoma.

Methods: Eligible literature was systematically retrieved from PubMed, Embase, and Web of Science databases. The pooled hazard ratios with 95% confidence intervals were used to evaluate to the effect. Raw data on HOTAIR expression were obtained from The Cancer Genome Atlas data portals. All bioinformatics analyses were performed using R software (version 4.3.1).

Results: We identified eight studies in this meta-analysis with a total of 399 patients. High-level HOTAIR expression was found to be significantly related to advanced tumor node metastasis stage, distant metastasis, poor tumor differentiation, and patients with hepatitis. Correspondingly, HOTAIR was also associated with poor overall survival and relapse-free survival. Subsequently, in bioanalysis, HOTAIR expression was higher in hepatocellular carcinoma as well as poor overall survival. High HOTAIR expression was strongly correlated with tumor node metastasis stage. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the differentially expressed genes related to HOTAIR may be involved in the cancer-associated signaling pathway.

Conclusion: HOTAIR may be a potential biomarker for HCC prediction and is expected to become a new choice for clinical HCC prediction..

Objectives: This study aimed to explore the value of D-dimer levels in predicting the treatment efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) treated with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors.

Methods: The study retrospectively analyzed 233 ESCC patients who received PD-1/PD-L1 inhibitors. The optimal cut-off values for platelets, fibrinogen, and D-dimer were calculated based on maximally selected rank statistics for patients' overall survival. Univariate and multivariate analyses of progression-free survival and overall survival were conducted by Cox proportional hazards regression model. Subgroup analyses of D-dimer levels in different fibrinogen levels were performed by log-rank test.

Results: The multivariate Cox regression analyses demonstrated that ESCC patients with D-dimer levels > 236 ng/mL exhibited both poorer progression-free survival (P = 0.004) and overall survival (P < 0.0001) compared to those with low D-dimer levels. The subgroup analyses further indicated that in the group of low fibrinogen levels, the higher D-dimer levels of ESCC patients exhibited significantly shorter progression-free survival (P = 0.0021) and overall survival (P < 0.0001).

Conclusions: The study revealed that the D-dimer levels possess predictive value for the treatment efficacy and prognosis of ESCC patients treated with PD-1/PD-L1 inhibitors.

Background: Early identification and therapy can significantly improve the outcome for gastric cancer. However, there is still no perfect biomarker available for the detection of early gastric cancer. This study aimed to investigate the alterations in the plasma metabolites of early gastric cancer using metabolomics and lipidomics based on high-performance liquid chromatography-mass spectrometry (HPLC-MS), which detected potential biomarkers that could be used for clinical diagnosis.

Methods: To investigate the changes in metabolomics and lipidomics, a total of 30 plasma samples were collected, consisting of 15 patients with early gastric cancer and 15 healthy controls. Extensive HPLC-MS-based untargeted metabolomic and lipidomic investigations were conducted. Differential metabolites and metabolic pathways were uncovered through the utilization of statistical analysis and bioinformatics analysis. Candidate biomarker screening was performed using support vector machine-based multivariate receiver operating characteristic analysis.

Results: A disturbance was observed in a combined total of 19 metabolites and 67 lipids of the early gastric cancer patients. The analysis of KEGG pathways showed that the early gastric cancer patients experienced disruptions in the arginine biosynthesis pathway, the pathway for alanine, aspartate, and glutamate metabolism, as well as the pathway for glyoxylate and dicarboxylate metabolism. Plasma metabolomics and lipidomics have identified multiple biomarker panels that can effectively differentiate early gastric cancer patients from healthy controls, exhibiting an area under the curve exceeding 0.9.

Conclusion: These metabolites and lipids could potentially serve as biomarkers for the screening of early gastric cancer, thereby optimizing the strategy for the detection of early gastric cancer. The disrupted pathways implicated in early gastric cancer provide new clues for additional understanding of gastric cancer's pathogenesis. Nonetheless, large-scale clinical data are required to prove our findings.