International Journal of Biological Markers最新文献

Proclarix is a new blood-based test to assess the likelihood of clinically significant prostate cancer (csPCa) defined as >2 grade group. In this study, we analyzed whether Proclarix and PSA density (PSAD) could improve the selection of candidates for prostate biopsy after multiparametric magnetic resonance imaging (mpMRI). Proclarix and PSAD were assessed in 567 consecutive men with suspected PCa in whom pre-biopsy 3 Tesla mpMRI, scoring with Prostate Imaging-Report and Data System (PI-RADS) v.2, and guided and/or systematic biopsies were performed. Proclarix and PSAD thresholds having csPCa sensitivity over 90% were found at 10% and 0.07 ng/(mL*cm³), respectively. Among 100 men with negative mpMRI (PI-RADS <3), csPCa was detected in 6 cases, which would have been undetected if systematic biopsies were avoided. However, Proclarix suggested performing a biopsy on 70% of men with negative mpMRI. In contrast, PSAD only detected 50% of csPCa and required 71% of prostate biopsies. In 169 men with PI-RADS 3, Proclarix avoided 21.3% of prostate biopsies and detected all 25 cases of csPCa, while PSAD avoided 26.3% of biopsies, but missed 16% of csPCa. In 190 men with PI-RADS 4 and 108 with PI-RADS 5, Proclarix avoided 12.1% and 5.6% of prostate biopsies, but missed 4.8% and 1% of csPCa, respectively. PSAD avoided 18.4% and 9.3% of biopsies, but missed 11.4% and 4.2% csPCa, respectively. We conclude that Proclarix outperformed PSAD in the selection of candidates for prostate biopsy, especially in men with PI-RADS <3.

Background: Emerging evidence suggests that circular RNAs (circRNAs) were aberrantly expressed in the patients of non-small cell lung cancer (NSCLC). This study aims to evaluate the diagnostic value of potential serum biomarker in circRNAs.

Methods: Serum circRNAs were extracted and purified by RNA isolated kit and identified by quantitative real time-polymerase chain reaction (qRT-PCR) assay. We then performed a receiver operating characteristic (ROC) curve to estimate the diagnostic efficacy. The relationship between circRNA and clinic characteristics of patients was analyzed by SPSS 25.0. Univariate and multivariate analyses were also used to evaluate its diagnostic capability. The mechanism of circFOXP1 was further excavated by bioinformatics analysis.

Results: By performing qRT-PCR assay, we identified that circFOXP1 (hsa_circ_0008234) and conventional tumor markers (carcinoembryonic antigen (CEA) and cytokeratin fragment 21-1 (CYFRA21-1)) were all significantly overexpressed in the serum of patients with NSCLC when compared with healthy controls (P < 0.05). While the ROC curves analysis demonstrated that area under the curve of circFOXP1 was obviously superior to CEA and CYFRA21-1, which exerted more diagnostic advantage. Univariate and multivariate analyses revealed that serum circFOXP1 was an independent diagnostic molecule, and was significantly correlated with T stage and lymphatic metastasis in NSCLC (P < 0.05). Mechanistically, circFOXP1 might target hsa-miR-370-3p and hsa-miR-18a-5p, and be involved in vascular endothelial growth factor signaling pathways to regulate proliferative and metastasis processes.

Conclusion: Our results highlight the preferable diagnostic potential of serum circFOXP1 in NSCLC.

Background: Death-associated protein kinase (DAPK) has a strong function of tumor suppression involving apoptosis regulation, autophagy, and metastasis inhibition. Hypermethylation of CpG islands in DAPK gene promoter region is one of the important ways to inactivate this tumor suppressor gene, which might promote lung carcinogenesis. However, the clinicopathological significance of the DAPK promoter hypermethylation in lung cancer remains unclear. In this study, we performed a meta-analysis trying to estimate the clinicopathological significance of DAPK promoter hypermethylation in non-small cell lung cancer (NSCLC).

Methods: A detailed literature search for publications relevant to DAPK gene promoter methylation and NSCLC was made in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, CSTJ, Wanfang databases, and SinoMed (CBM). The random-effects model and fixed-effects model were utilized to pool the relative ratio based on the heterogeneity test in the meta-analysis.

Results: A total of 41 studies with 3348 patients were included. The frequency of DAPK methylation was significantly higher in NSCLC than in non-malignant control (odds ratio (OR) = 6.88, 95% confidence interval (CI):  4.17-11.35, P < 0.00001). The pooled results also showed that DAPK gene promoter hypermethylation was significantly associated with poor prognosis for overall survival in patients with NSCLC (hazard ratio: 1.23, 95% CI:1.01-1.52, P = 0.04). Moreover, DAPK gene promoter hypermethylation was significantly associated with squamous cell carcinoma (OR: 1.25, 95% CI: 1.01-1.54, P = 0.04) and smoking behavior (OR: 1.42, 95% CI: 1.04-1.93, P = 0.03) but not with TNM stage, tumor differentiation, age, or gender.

Conclusion: DAPK promoter hypermethylation might be a candidate diagnostic and prognostic tumor marker for NSCLC.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which play critical roles in cancer progression and metastasis. In recent years, many researchers have been studying the relationship between MMP9 and breast cancer. However, it still remains indecisive. Therefore, we conducted a meta-analysis to draw more accurate conclusions. A total of 21 relevant documents were retrieved, including 25 case-control studies. We quantitatively analyzed the data obtained. To clarify the relationship between MMP9 polymorphism and breast cancer susceptibility under different conditions, we also made a further subgroup analysis for each locus. In summary, we discovered that MMP9 rs3918242 rendered an increased risk for breast cancer, especially among Iranians and Indians. MMP9 rs3787268 could be a protective factor. MMP9 rs17576 and MMP9 rs2250889 have no association with breast cancer risk.

Background: Accumulating evidence has indicated that runt-related transcription factor 3 (RUNX3) gene polymorphism (rs7528484) is associated with an alimentary system cancer risk. However, the role of rs7528484 in colorectal cancer is still unclear. The present study aimed to explore the association between rs7528484 and colorectal cancer susceptibility in a Chinese Han population.

Material and methods: We firstly investigated the effect of the polymorphism rs7528484 in distal promoter of RUNX3 polymorphism on colorectal cancer risk in a Chinese Han population comprising 427 colorectal cancer patients and 503 controls. We then carried out a phenotype-genotype association analysis to validate its influence on the adjacent gene RUNX3.

Results: Logistic regression analysis demonstrated that the T allele of rs7528484 was significantly associated with an increased risk for colorectal cancer occurrence in our case-control study (odds ratio = 1.33; 95% confidence interval = 1.09-1.65; P = 0.005). In stratified analysis, the susceptibility of colorectal cancer in the T allele carriers increased among the smokers, III and IV tumor stage, and at the rectum. Furthermore, the T allele was significantly correlated with lower expression of RUNX3 in vitro.

Conclusion: In summary, the current case-control and genotype-phenotype study provides convincing evidence that functional RUNX3 polymorphism (rs7528484) is related to colorectal cancer risk and is a plausible marker for the prediction of colorectal cancer.

Introduction: Carbohydrate antigen 19-9 (CA19-9) is a well-studied tumor marker, yet its diagnostic value for gallbladder cancer remains unclear. The present meta-analysis was conducted to validate the role of serum CA19-9 for the detection of gallbladder cancer.

Methods: A systematic search of digital databases was conducted, complemented by additional hand-searching. Studies that reported serum CA19-9 for the differentiation of gallbladder cancer cases from non-gallbladder cancer controls were considered eligible.

Results: A total of 27 studies involving 4300 subjects were included. The pooled sensitivity, specificity, and area under the curve in diagnosing gallbladder cancer were 0.70 (95% confidence interval (CI): 0.63-0.76), 0.92 (95% CI: 0.88-0.94), and 0.89 (95% CI: 0.86-0.92), respectively. The pooled positive likelihood rate, negative likelihood rate, and diagnostic odds rate were 8.30 (95% CI: 5.84-11.69), 0.33 (95% CI: 0.27-0.41), and 25.13 (95% CI: 5.83-39.89), respectively. Meta-regression analysis revealed that there was significantly lower sensitivity (0.69, 95% CI: 0.61-0.77) and specificity (0.91, 95% CI: 0.87-0.95) when CA19-9 was used for the differentiation of gallbladder cancer cases from benign biliary diseases. A better specificity of 0.93 (95% CI: 0.90-0.96) was reached in the setting of a sample size ≥100.

Conclusions: Serum CA19-9 can be a potential candidate marker for the detection of gallbladder cancer, which maintains moderate sensitivity and good specificity. Attention should be paid to the control type and sample size, which may affect its diagnostic accuracy. Also, results should be interpreted with caution due to significant heterogeneity primarily caused by different thresholds between included studies.

Objectives: The aim of this study was to explore the diagnostic efficiency of serum exosomal miR-451a as a novel biomarker for pancreatic cancer.

Methods: Serum samples were collected prior to treatment. First, we analyzed microRNA (miRNA) profiles in serum exosomes from eight pancreatic cancer patients and eight healthy volunteers. We then validated the usefulness of the selected exosomal miRNAs as biomarkers in another 191 pancreatic cancer patients, 95 pancreatic benign disease (PB) patients, and 90 healthy controls.

Results: The expression of miR-451a in serum-derived exosomes from pancreatic cancer patients was significantly upregulated compared with those from PB patients and healthy individuals. Serum exosomal miR-451a showed excellent diagnostic power in identifying pancreatic cancer patients. In addition, exosomal miR-451a showed a significant association with clinical stage and distant metastasis in pancreatic cancer, and the expression level of serum exosomal miR-451a was sensitive to therapy and relapse.

Conclusions: Serum exosomal miR-451a might serve as a novel diagnostic marker for pancreatic cancer.

Background: RASSF1A is a tumor suppressor gene. The methylation of RASSF1A has been reported to be associated with nasopharyngeal tumorigenesis. However, the heterogeneity was high among different studies. A meta-analysis was performed to evaluate the value of RASSF1A methylation for the diagnosis and early screening of nasopharyngeal carcinoma.

Methods: Relevant articles were identified by searching the MEDLINE database. Frequency and odds ratio (OR) were applied to estimate the effect of CDH-1 methylation based on random-/fixed-effect models. The meta-analysis was performed by using MedCalc^® software. Subgroup analyses were performed by test method, ethnicity, and source of nasopharyngeal carcinoma samples to determine likely sources of heterogeneity.

Results: A total of 17 studies, including 1688 samples (1165 nasopharyngeal carcinoma samples, and 523 from non-cancerous samples) were used for the meta-analysis. The overall frequencies of RASSF1A methylation were 59.68% and 2.65% in case-group and control-group, respectively. By removing the poor relative studies, the heterogeneity was not observed among the studies included. The association between RASSF1A gene methylation and the risk of nasopharyngeal carcinoma was also confirmed by calculating the OR value of 30.32 (95%CI  = 18.22-50.47) in the fixed-effect model (Q = 16.41, p = 0.36,I² = 8.62, 95% CI = 0.00-45.27). Additionally, the significant association was also found between the methylation of the RASSF1A gene and the subgroups.

Conclusions: This is the first meta-analysis that has provided scientific evidence that the methylation of RASSF1A is the potential diagnosis, prognosis, and early screening biomarker for nasopharyngeal carcinoma.

Small nucleolar RNA host gene 3 (SNHG3), as a novel long non-coding RNA (lncRNA) participates in the oncogenic processes of various cancers. We combined a systematic review and a meta-analysis to assess the potential role of SNHG3 as a pan-cancer marker for cancer diagnosis and prognosis. Our study comprehensively searched for SNHG3 expression profiling studies from PubMed, Web of Science, Excerpta Medica Database (EMBASE), Cochrane Library, Google Scholar, and The Cancer Genome Atlas (TCGA). The diagnostic capacity of SNHG3 for all cancers in TCGA database was evaluated from the perspective of pooled sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC) of the summary receiver operating characteristic (sROC) curve. Also, this research studied the correlation of SNHG3 expression and the overall survival to access its prognostic value. A sum total of 11,888 cancer patients and 730 controls from 44 eligible studies were enrolled in this integrated analysis. In TCGA database, SNHG3 was significantly upregulated in most types of cancers (16/33, 48%). The pooled sensitivity, specificity, and DOR with 95% CIs was 0.72 (95% CI: 0.60-0.82), 0.87 (95% CI: 0.84-0.90), and 18 (95% CI: 11-30), respectively. Similarly, the AUC of the sROC curve was 0.89 (95% CI: 0.86-0.92), indicating SNHG3 was highly conserved as a diagnosis biomarker. Additionally, SNHG3 overexpression significantly deteriorated the overall survival of cancer patients (pooled HR = 1.28, 95% CI:1.11-1.48; P < 0.05). These findings suggest that the lncRNA SNHG3 could serve as a promising diagnostic and prognostic biomarker.