International Journal of Biological Markers最新文献

Background: The relationship between serum uric acid and breast cancer remains uncertain. This meta-analysis aimed to elucidate the dose-response association between elevated serum uric acid levels and breast cancer risk.

Methods: We systematically searched PubMed, Embase, and Web of Science for observational studies evaluating serum uric acid and breast cancer risk in adult women. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model.

Results: Ten studies were included. High serum uric acid was associated with an increased breast cancer risk (RR: 1.34; 95% CI: 1.03-1.73; P = 0.03; I² = 78%). Meta-regression analysis revealed that the cutoff for high serum uric acid positively correlated with breast cancer risk (coefficient = 0.24; P < 0.001), explaining heterogeneity (residual I² = 0%). Subgroup analysis demonstrated a high serum uric acid was significantly related to an increased breast cancer risk in studies with a cutoff value ≥ 5.4 mg/dL (RR: 1.95; P < 0.001), but not in those with a cutoff value < 5.4 mg/dL (RR: 0.97; P = 0.44). The dose-response meta-analysis revealed a U-shaped association between serum uric acid levels and the risk of breast cancer (P for nonlinearity = 0.013). The risk of breast cancer fell until around 4.5 mg/dL of serum uric acid, and increased afterward.

Conclusion: Serum uric acid may be nonlinearly associated with the risk of breast cancer (U-shaped). The risk of breast cancer increases with serum uric acid above 4.5 mg/dL, and a higher association between serum uric acid and the increased risk of breast cancer could be observed in studies with cutoff of serum uric acid  > 5.4 mg/dL.

Background: Liver metastasis and chemotherapy resistance are two unfavorable factors for the outcomes of gastric cancer patients. ADHFE1 was identified as cancer-related molecule and candidate for early detection in gastric cancer. This study evaluated the significance of ADHFE1 in gastric cancer, aiming to explore a potential biomarker and therapeutic target for gastric cancer.

Methods: The expression of ADHFE1 was detected by polymerase chain reaction and compared between 143 gastric cancer patients and 54 individuals with benign lesions. The role of ADHFE1 in gastric cancer development and prognosis was assessed. The effect of ADHFE1 on gastric cancer cell growth and motility was evaluated by cell counting kit-8 and Transwell assay. The angiogenesis and cisplatin resistance were assessed by related markers and the half maximal inhibitory concentration values.

Results: Significant upregulation of ADHFE1 was observed in gastric cancer patients compared to individuals with benign lesions, which showed close association with the tumor node metastasis stage, lymph node metastasis, liver metastasis, and adverse prognosis of gastric cancer patients. Patients with liver metastasis showed higher serum ADHFE1 levels, which decreased after chemotherapy. Silencing ADHFE1 significantly suppressed gastric cancer cell proliferation, migration, invasion, and angiogenesis while its overexpression showed opposite effects. Moreover, the overexpression of ADHFE1 significantly improved the cisplatin resistance of gastric cancer cells.

Conclusion: Serum ADHFE1 served as an indicator for poor prognosis and liver metastasis of gastric cancer. ADHFE1 regulates gastric cancer cell progression, cisplatin resistance, and angiogenesis, suggesting its potential to serve as a therapeutic target.

Purpose: We aimed to exploit a urine exosomal long non-coding RNAs (lncRNAs) fingerprint to facilitate the early diagnosis of bladder cancer.

Methods: Microarray differential expression profiling of lncRNAs was for the first time employed in urine exosomes from 10 non-muscle-invasive bladder cancer (NMIBC) patients and 10 healthy controls to screen out candidate exosomal lncRNA biomarkers, which were then verified by quantitative real-time polymerase chain reaction in three independent phases including bladder cancer cells, culture fluid and 200 NMIBC participants. Logistic regression was performed to construct a diagnostic model-the diagnostic potency of which was assessed.

Results: The profile of three exosome-derived lncRNAs (CCDC148-AS1, XLOC_006419, and RP5-1148A21.3) was screened and further verified to be notably over-expressed in NMIBC patients and bladder cancer cell lines, and exhibited area under the receiver-operating characteristic curve values of 0.873, 0.825, and 0.834, respectively, in training, validation, and double-blind validation phases. The profile was superior to urinary cytology in discriminating NMIBC from healthy controls (P < 0.0001). A significant correlation existed between a higher level of CCDC148-AS1 and a higher tumor grade (P < 0.001), and up-regulated CCDC148-AS1 as well as XLOC_006419 were statistically related with tumor node metastasis stage (P = 0.004 and P = 0.031, respectively). These three identified lncRNAs were confirmed to originate from bladder cancer cells and be packaged within exosomes, thus staying sufficiently stable in urine.

Conclusions: Tumor-originated urine exosomal lncRNAs, as fingerprint in NMIBC, exhibited satisfying clinical significance in early diagnosis of bladder cancer.

Introduction: Breast cancer is the most common cancer among women, and metabolic syndrome (MetS) is a risk factor for breast cancer, especially postmenopausal breast cancer. We evaluated the role of the advanced glycated end products (AGEs) levels contributing to the association between MetS and breast cancer risk.

Methods: Plasma AGEs were measured in a case-control study nested within the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort, including 40 incident postmenopausal breast cancer cases (20 with MetS and 20 without) and 40 postmenopausal controls (20 with MetS and 20 without). The association between AGEs and breast cancer was analyzed using Bayesian logistic regression models. An informative prior for the exposure coefficient, modeled as a normal distribution, centered on the natural logarithm of an odds ratio ((OR)=1.635) derived from prior evidence, was employed alongside weakly informative priors (WIPs). Bayesian linear regression with WIPs was used to examine the association between MetS and AGEs. Estimates were reported with SDs and 90% and 95% credible intervals (CI).

Results: AGEs were associated with higher breast cancer risk both with the informative prior (OR = 1.745, SD):0.362; 90% CI:1.218-2.390; 95% CI:1.137-2.548) and the WIP (OR = 1.861, SD = 0.661; 90% CI:1.026-3.082; 95% CI:0.924-3.528) specification. Although the difference in plasma AGEs in women with and without MetS was not significant, we found a suggestion of higher levels in women with MetS (mean difference in standardized AGEs between individuals with and without MetS = 0.155, SD = 0.245; 90% CI:-0.246 to 0.553; 95% CI:-0.322 to 0.625).

Conclusions: These data, although from a small sample of women, support a role of endogenous AGEs in the pathological pathways underlying the association between MetS and breast cancer development.

Purpose: To detect the prognostic importance of liquid-liquid phase separation (LLPS) in lung adenocarcinoma.

Methods: The gene expression files, copy number variation data, and clinical data were downloaded from The Cancer Genome Atlas cohort. LLPS-related genes were acquired from the DrLLPS website. The prognostic model based on LLPS was constructed by the Cox regression and LASSO regression analyses after the identification of LLPS-related differentially expressed genes (DEGs). Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed. The LLPS-related prognostic risk score was validated by GSE31210 and GSE72094. The overall survival of lung adenocarcinoma patients was predicted by plotting a nomogram. The biological features of the high-risk lung adenocarcinoma were evaluated by the CIBERSORT, ESTIMATE, Gene Set Variation Analysis, and Genomics of Drug Sensitivity in Cancer. Reverse transcription-quantitative polymerase chain reaction detected hub gene expression.

Results: A total of 91 DEGs were screened out in LLPS, among which 9 genes were discovered as prognostic biomarkers of lung adenocarcinoma. GRIA1, CRTAC1, MAGEA4, and MAPK4 were identified as hub genes by the LASSO Cox regression analysis. High-risk and low-risk groups were divided according to the risk index, with the high-risk group displaying a markedly worse outcome. CRTAC1 expression was significantly decreased, MAGEA4 and MAPK4 expressions were increased, while GRIA1 expression was altered in lung adenocarcinoma cells. Tumor microenvironment, signaling pathway enrichment, and drug sensitivity significantly differed between different risk groups.

Conclusions: This work proposed a prognostic tool based on the LLPS-related gene signature to offer prospective and effective biomarkers for lung adenocarcinoma prognosis.

Background: This study aims to investigate the mutation status and protein expression of low-density lipoprotein receptor-related protein 1B (LRP1B) in endometrial cancer, and analyze its association with lymph node metastasis (LNM) in endometrial cancer.

Methods: Targeted next-generation sequencing (NGS) was conducted on both tumor tissues and paired blood DNA obtained from 94 endometrial cancer patients, followed by comprehensive analysis. Additionally, immunohistochemistry (IHC) was used to explore the correlation between LRP1B protein expression levels, its gene mutation status, and LNM.

Results: LRP1B mutation was observed in 19 patients (20.2%). Our results revealed that LRP1B mutation frequencies were significantly different between endometrial cancer with or without LNM (P = 0.038). Multivariate analysis indicated that LRP1B mutation was a favorable predictor (odds ratio 0.09; 95% confidence interval 0.01-0.95; P = 0.045) for LNM in endometrial cancer. Further analysis revealed that combination of LRP1B mutation with clinical variants (LVSI and histological subtype) yielded a higher area under the curve value of 0.871) and patients harboring LRP1B mutated-type were less likely to develop LNM. On integrated analysis, the concordance between LRP1B NGS and LRP1B IHC was 73.3%.

Conclusions: This study utilizes targeted NGS to uncover the relationship between LRP1B mutation and LNM status, contributing to the development of primary prevention and proactive treatment strategies.

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.

Objective: The poor prognosis of cervical cancer patients leads to an annual increase in mortality, while microRNAs are involved in various cancers, including cervical cancer. This study aimed to investigate the clinical value and possible effect of miR-29b-2-5p on the progression of cervical cancer.

Methods: The expression level of miR-29b-2-5p in cervical cancer tissues and cells was analyzed by polymerase chain reaction. The Kaplan-Meier curve was used to evaluate the role of miR-29b-2-5p in cervical cancer prognosis. The independent prognostic factors of cervical cancer were explored by the multivariate Cox regression analysis. The effect of miR-29b-2-5p on the proliferation, migration, and invasion of cervical cancer cells was determined by in vitro cell experiments.

Results: A significantly downregulated miR-29b-2-5p expression was observed in cervical cancer tumor tissues and cervical cancer cells compared with the adjacent tumor tissues (tissues of the negative surgical margin) and H8 cells, respectively. Higher miR-29b-2-5p expression correlated with a better 5-year progression-free survival of cervical cancer. MiR-29b-2-5p was also associated with the indicators (tumor size, tumor differentiation, FIGO (International Federation of Gynecology and Obstetrics) stage, and invasion depth) of the progression of cervical cancer tumors. And miR-29b-2-5p, along with tumor size, tumor differentiation, FIGO stage, histology type, and invasion depth, were independent prognostic factors for poor cervical cancer prognosis. MiR-29b-2-5p showed a suppressive effect on the proliferation, migration, and invasion of cervical cancer cells.

Conclusions: MiR-29b-2-5p was downregulated in cervical cancer tumor tissues and could serve as an independent prognostic factor for cervical cancer. The overexpressed miR-29b-2-5p could be considered a tumor suppressor to inhibit the progression of cervical cancer.

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.

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.