International Journal of Biological Markers最新文献

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.

Background: Colorectal cancer (CRC) is often diagnosed late and has a poor prognosis. Circular RNAs (circRNAs) have been identified as prognostic biomarkers in various cancers, including CRC.

Objective: The objective was to elucidate the role of circLPHN3 (hsa_circ_0069865) in CRC progression and to provide a promising prognostic marker for CRC.

Methods: CircLPHN3 was identified through bioinformatics analysis of the GSE121842 dataset. The levels of circLPHN3 in CRC samples were analyzed by real time-quantitative polymerase chain reaction. Its clinical significance was assessed using the Kaplan-Meier curve and multivariate Cox regression. Downstream microRNAs of circLPHN3 were predicted with the RNAhybrid, Circular RNA Interactome, and starBase online databases. The target of miR-142-5p was predicted using miRDB, TargetScanHuman, starBase, and miRWalk databases. The relationship between circLPHN3, miR-142-5p, and LDB2 was verified by dual luciferase reporter assay. The function of circLPHN3 on CRC cell growth and metastasis was measured using Transwell and the cell counting kit-8 assay.

Results: Significant downregulation of circLPHN3 was found in CRC. CircLPHN3 was closely related to higher tumor node metastasis stage, lymph node metastasis, and predicted unfavorable prognosis. miR-142-5p was highly expressed in CRC and its expression was negatively regulated by circLPHN3. Overexpression of circLPHN3 curbed CRC cell growth, migration, and invasion, mediated by miR-142-5p. Moreover, LDB2 was identified as a target of miR-142-5p.

Conclusion: CircLPHN3 acted as a prognostic biomarker and tumor suppressor for CRC via modulating miR-142-5p.

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.

Objective: Multiple myeloma (MM) is a plasma cell malignancy characterized by abnormal plasma cell proliferation in the bone marrow. Circulating exosomal miRNA-451 is associated with the progression of many tumors, but the relationship between its expression and MM has not been reported. In this study, we aimed to investigate the clinical value of miRNA-451 as a biomarker for diagnosis and prognosis of multiple myeloma.

Methods: A total of 120 patients with multiple myeloma and 120 healthy control people were recruited in this study. The miRNA-451 expression in serum exosomes of participants was measured by quantitative real-time polymerase chain reaction, and the diagnostic value of miRNA-451 for multiple myeloma was assessed by receiver operating characteristic (ROC) curve. The correlation between miRNA-451 expression and plasma cells ratio and M protein content was analyzed by Pearson correlation coefficient. The prognosis of different miRNA-451 expression was evaluated by survival curves.

Results: Results suggested that serum exosomal miRNA-451 expression was significantly decreased in patients with multiple myeloma rather than in the healthy controls. The ROC curve showed that area under the curve value of miRNA-451 was 0.888, suggesting that miRNA-451 had diagnostic value to multiple myeloma. Moreover, there was a negative correlation between miRNA-451 expression and plasma cells ratio or M protein content. Survival curves showed that patients with high miRNA-451 expression had a longer survival time, suggesting the value of miRNA-451 as a prognostic indicator of multiple myeloma.

Conclusion: We demonstrated the relationship between miRNA-451 expression and multiple myeloma, indicating that miRNA-451 in circulating exosomes may be an effective diagnostic biomarker and prognostic indicator for multiple myeloma.

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: Exploring effect biomarkers that monitor tumor progression and predict the prognosis could benefit the clinical management of bladder cancer and improve the postoperative life of patients. This study aimed to estimate the function of long non-coding (lnc)RNA RHPN1-AS1 (RHPN1-AS1) in bladder cancer and the potential molecular mechanism.

Methods: The expression of RHPN1-AS1 was evaluated in bladder cancer tissues from 115 patients and cells by polymerase chain reaction. The clinical significance of RHPN1-AS1 was assessed and its effect was also estimated in cell proliferation, migration, and invasion. The underlying molecular mechanism was explored by the dual-luciferase reporter assay.

Results: The expression of RHPN1-AS1 was 2.91-fold elevated in bladder cancer, which showed a close correlation with advanced tumor node metastasis stage (P = 0.013) and the presence of lymph node metastasis (P = 0.018). RHPN1-AS1 also served as a poor prognostic indicator (hazard ratio = 2.563) for bladder cancer. The knockdown of RHPN1-AS1 significantly suppressed the proliferation and metastasis ability of bladder cancer cells. Moreover, miR-485-5p was found to mediate the function of RHPN1-AS1 in bladder cancer, which was considered the underlying regulatory mechanism.

Conclusions: RHPN1-AS1 serves as a prognostic biomarker and tumor promoter in bladder cancer via modulating miR-485-5p, which might be a reliable target of bladder cancer therapy.

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.