Diagnostic performance of circulating exosomes in human cancer: A meta-analysis.

BACKGROUND: Cancer has become a public health problem with high morbidity and mortality. Recent publications have shown that exosomes can be used as potential diagnostic biomarkers of cancer. However, the diagnostic accuracy and reliability of circulating exosomes remain unclear. The present meta-analysis was conducted to comprehensively summarize the overall diagnostic performance of circulating exosomes for cancer. METHODS: Eligible studies published up to June 27, 2019, on PubMed, Embase, and Cochrane Library were selected for the meta-analysis. All statistical analyses were performed by STATA 15.1 statistical software and Meta-DiSc 1.4. Quality Assessment for Studies of Diagnostic Accuracy 2 tool was used to access the quality of included studies. A bivariate mixed-effects model was applied to calculate the diagnostic indexes from included studies. RESULTS: A total of 5924 participants comprising 3161 cases and 2763 controls from 42 eligible studies were analyzed. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under the curve with 95% confidence intervals (95% CI) were as follows: 0.79 (0.75-0.82), 0.81 (0.78-0.84), 4.1 (3.5-4.8), 0.26 (0.22-0.31), 16 (12-21), and 0.87 (0.84-0.89), respectively. Sensitivity analysis suggested no study exclusively contributed to the heterogeneity, and Deeks' funnel plot asymmetry test indicated no potential publication bias (P = .09). CONCLUSIONS: The meta-analysis indicated that circulating exosomes could serve as effective and minimally invasive biomarkers for diagnosis of cancer, especially in patients with hepatocellular carcinoma or ovarian cancer, serum-based samples and exosomal proteins.

Differences in oncological outcomes and inflammatory biomarkers between right-sided and left-sided stage I-III colorectal adenocarcinoma.

BACKGROUND: The aim of this study was to investigate the differences in oncological outcome and inflammatory biomarkers between right-sided colon cancer (RCC) and left-sided colorectal cancer (LCRC). METHODS: We retrospectively analyzed 339 patients with stage I-III colorectal cancer, including 125 RCC patients and 214 LCRC patients, who underwent radical resection from January 2012 to January 2014. Comparison of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) between RCC and LCRC was evaluated using the Mann-Whitney U test. Overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan-Meier analysis and compared using the log-rank test. Univariate and multivariate Cox regression analyses were used to identify the prognostic value of inflammatory markers. RESULTS: Patients with RCC had higher NLR (P = .002) and PLR (P < .001) but lower LMR (P = .002) compared to LCRC. In stage I-III, RCC showed poorer OS and DFS than LCRC (61.6% vs 71.5%, P = .018; 64.8% vs 76.2%, P = .006). Univariate and multivariate analyses indicated that NLR, PLR, and LMR were independent predictors for both OS and DFS in RCC, whereas only PLR was found to be an independent prognostic predictor in LCRC. CONCLUSION: The prognosis and prognostic value of inflammatory biomarkers were significantly different between RCC and LCRC. Novel therapeutic strategies are needed, and proper prognostic predictors should be selected according to colorectal tumor location.

Aberrant ARMCX1 Expression Is an Independent Predictor of Poor Prognosis in Gastric Cancer.

ARMCX1 (Armadillo repeat containing X-linked 1) is identified to be the novel tumor suppressor gene related to multiple tumor types. Nonetheless, its effect on gastric cancer (GC) is still poorly understood. The present work determined ARMCX1 level within GC and the relation with clinicopathological characteristics. This work also collected relevant information in The Cancer Genome Atlas (TCGA) database for investigating associations of ARMCX1 with clinicopathologic variables and then validated in our GC cohort. Receiver operating characteristic (ROC) curves were plotted for assessing whether ARMCX1 expression was significant in diagnosing GC. Kaplan-Meier (KM) and Cox regression analyses were conducted for assessing clinicopathological characteristics associated with overall survival (OS) of GC cases. The data from the Human Protein Atlas (HPA) and Gene Expression Omnibus (GEO) databases was also analyzed for further validation, and biological processes (BPs) were identified by gene set enrichment analysis (GSEA). GC tissues showed markedly decreased ARMCX1 level relative to healthy counterparts (P < 0.001). Interestingly, ARMCX1 upregulation predicted low differentiation, poor OS, increased invasion, and late tumor stage. In addition, the area under ROC curve (AUC) and P value were 0.747 and <0.001, separately. Cases showing ARMCX1 upregulation showed significantly poor prognostic outcome compared with patients showing downregulation (P = 0.007). Furthermore, multivariate analysis showed that ARMCX1 upregulation independently predicted the risk of OS (P = 0.0017, hazard ratio, 1.089). GSEA analysis identified that several cancer-related pathways, such as focal adhesion, ECM receptor interaction, JAK/STAT, melanoma, WNT, and cancer, were enriched in GCs. We conclude that ARMCX1 serves as the possibly independent biomarker to diagnose and predict GC prognostic outcome.

Clinical correlations and prognostic value of Nudix hydroxylase 10 in patients with gastric cancer.

Gastric cancer (GC) is one of the most common and lethal cancers worldwide. The Nudix hydroxylase (NUDT) genes have been reported to play notable roles in tumor progression. However, the role of NUDT10 in GC has not been reported. In this study, we investigated the expression of NUDT10 in GC and its association with clinicopathological characteristics. Quantitative real-time polymerase chain reaction and analyses of The Cancer Genome Atlas and Human Protein Atlas databases were performed to determine NUDT10 mRNA and protein expression. Receiver operating characteristic curve analysis was used to assess the diagnostic value of NUDT10 in patients with GC. We used Cox regression and the Kaplan-Meier method to assess the correlations between clinicopathological factors and survival outcomes of patients with GC. Gene set enrichment analysis (GSEA) was performed to identify the underlying signaling pathways. NUDT10 mRNA and protein expression was significantly lower in GC tissues compared to normal tissues. Interestingly, higher NUDT10 expression was correlated with advanced tumor stage, deeper local invasion, and worse survival outcomes. Patients with higher NUDT10 expression had a significantly worse prognosis than those with lower NUDT10 expression. Multivariate analysis showed that high NUDT10 expression was an independent predictor of survival outcome. Several pathways, including mismatch repair, nucleotide excision repair, extracellular matrix receptor interaction, and cancer signaling, were identified as enriched pathways in GC through GSEA. To our knowledge, this study is the first to characterize NUDT10 expression in GC. Our study demonstrates that NUDT10 is a promising independent biomarker for GC prognosis.

MicroRNA­383­5p inhibits the proliferation and promotes the apoptosis of gastric cancer cells by targeting cancerous inhibitor of PP2A.

The aberrant expression of microRNA (miRNAor miR)­383­5p has been found in numerous types of cancer. However, the function of miR­383­5p in gastric cancer (GC) remains elusive and requires further investigation. In the present study, the level of miR­383­5p and cancerous inhibitor of PP2A (CIP2A) in GC cell lines was determined by reverse transcription­quantitative PCR analysis. GC cell proliferation, apoptosis and cell cycle distribution were determined by the MTT assay and flow cytometry, respectively. The mRNA target of miR­383­5p was identified by dual luciferase activity assay. It was observed that the expression of miR­383­5p was lower and that of CIP2A was higher in GC cells compared with the GES­1 normal human gastric epithelial cell line. Transfectoin with miR­383­5p mimic significantly inhibited GC cell proliferation, while it promoted cell apoptosis and G0/G1 arrest by targeting CIP2A. Taken together, the findings of the present study demonstrate that miR­383­5p inhibits GC cell proliferation and promotes apoptosis and G0/G1 arrest by targeting CIP2A, indicating that targeting miR­383­5p may hold promise as a future therapeutic strategy for patients with GC.

INHBB Is a Novel Prognostic Biomarker Associated with Cancer-Promoting Pathways in Colorectal Cancer.

BACKGROUND: Inhibin subunit beta B (INHBB) is a protein-coding gene that participated in the synthesis of the transforming growth factor-ß (TGF-ß) family members. The study is aimed at exploring the clinical significance of INHBB in patients with colorectal cancer (CRC) by bioinformatics analysis. METHODS: Real-time PCR and analyses of Oncomine, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases were utilized to evaluate the INHBB gene transcription level of colorectal cancer (CRC) tissue. We evaluated the INHBB methylation level and the relationship between expression and methylation levels of CpG islands in CRC tissue. The corresponding clinical data were obtained to further explore the association of INHBB with clinical and survival features. In addition, Gene Set Enrichment Analysis (GSEA) was performed to explore the gene ontology and signaling pathways of INHBB involved. RESULTS: INHBB expression was elevated in CRC tissue. Although the promoter of INHBB was hypermethylated in CRC, methylation did not ultimately correlate with the expression of INHBB. Overexpression of INHBB was significantly and positively associated with invasion depth, distant metastasis, and TNM stage. Cox regression analyses and Kaplan-Meier survival analysis indicated that high expression of INHBB was correlated with worse overall survival (OS) and disease-free survival (DFS). GSEA showed that INHBB was closely correlated with 5 cancer-promoting signaling pathways including the Hedgehog signaling pathway, ECM receptor interaction, TGF-ß signaling pathway, focal adhesion, and pathway in cancer. INHBB expression significantly promoted macrophage infiltration and inhibited memory T cell, mast cell, and dendritic cell infiltration. INHBB expression was positively correlated with stromal and immune scores of CRC samples. CONCLUSION: INHBB might be a potential prognostic biomarker and a novel therapeutic target for CRC.