Prognostic utility and clinical significance of lysyl oxidase-like 2 protein expression in digestive system cancers.

Lysyl oxidase-like 2 (LOXL2) participates in the occurrence and development of digestive system cancers (DSCs). The aim of this study was to determine whether LOXL2 protein could serve as a prognostic biomarker in patients with DSCs. Relevant studies published before October 1, 2018 were identified from a comprehensive literature review in PubMed, Web of Science, and Embase. This meta-analysis was conducted via STATA/SE 14.1 software. Finally, a total of 12 publications and 6 different kinds of DSCs were identified. Meta-analysis indicated that increased expression of LOXL2 protein was significantly correlated with reduced overall survival (hazard ratios [HR]: 1.52; 95% confidence interval [CI]: 1.32-1.72) and worse progression-free survival/disease-free survival (HR: 2.15; 95% CI: 1.48-2.83) in cases with DSCs. In addition, clinicopathological parameters, including tumor invasion, lymph node metastasis, distant metastasis, and clinical stage were significantly related to LOXL2 protein expression in DSCs. High LOXL2 protein expression is significantly associated with worse clinical outcomes in DSCs and its expression level may represent a candidate prognostic biomarker in these cancers.

Diagnostic and Prognostic Value of Methyltransferase Like 13 in Hepatocellular Carcinoma Based on Bioinformatics Analysis.

BACKGROUND/AIMS:  Hepatocellular carcinoma (HCC) is one of the cancers with the highest incidence and mortality rates. This study aims to explore the diagnostic and prognostic utility of methyltransferase like 13 (METTL13) in patients with HCC via bioinformatics analysis. MATERIALS AND METHODS:  We obtained mRNA data of HCC from the database of the Cancer Genome Atlas (TCGA), drawing survival curve by R 4.2.1 software. Cox regression analysis was conducted based on tumor stage and METTL13 expression. The GSE114564 dataset was chosen from the Gene Expression Omnibus. The differences in serum METTL13 levels between the groups of early HCC (eHCC) and non-cancer controls were evaluated. Using a receiver operating characteristic curve, we calculated the area under the curve (AUC) of serum METTL13 for diagnosing eHCC. RESULTS:  A total of 225 cases with HCC were screened from TCGA, and 29 cases were normal controls. The results showed that the METTL13 expression in the HCC group was higher than that in the normal controls (P <.001). The univariate [hazard ratio (HR) = 1.895, P = .006] and multivariate Cox regression (HR = 1.702, P = .037) analyses showed that high METTL13 expression reduced overall survival in HCC. Serum METTL13 levels were higher in the eHCC group than in the non-cancer controls (P = .008). The optimum AUC for predicting eHCC by serum METTL13 was 0.7091. CONCLUSION:  Serum METTL13 has a moderate diagnostic value for eHCC. High METTL13 expression is correlated with a worse prognosis in patients with HCC. Methyltransferase like 13 possesses the potential to be a novel biomarker for HCC.

Salivary microbiota may predict the presence of esophageal squamous cell carcinoma.

The aim is to explore the predictive value of salivary bacteria for the presence of esophageal squamous cell carcinoma (ESCC). Saliva samples were obtained from 178 patients with ESCC and 101 healthy controls, and allocated to screening and verification cohorts, respectively. In the screening phase, after saliva DNA was extracted, 16S rRNA V4 regions of salivary bacteria were amplified by polymerase chain reaction (PCR) with high-throughput sequencing. Highly expressed target bacteria were screened by Operational Taxonomic Units clustering, species annotation and microbial diversity assessment. In the verification phase, the expression levels of target bacteria identified in the screening phase were verified by absolute quantitative PCR (Q-PCR). Receiver operating characteristic (ROC) curves were plotted to investigate the predictive value of target salivary bacteria. LEfSe analysis revealed higher proportions of Fusobacterium, Streptococcus and Porphyromonas, and Q-PCR assay showed significantly higher numbers of Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in patients with ESCC, when compared with healthy controls (all P < 0.05). The areas under the ROC curves for Streptococcus salivarius, Fusobacterium nucleatum, Porphyromonas gingivalis and the combination of the three bacteria for predicting patients with ESCC were 69%, 56.5%, 61.8% and 76.4%, respectively. The sensitivities corresponding to cutoff value were 69.3%, 22.7%, 35.2% and 86.4%, respectively, and the matched specificity were 78.4%, 96.1%, 90.2% and 58.8%, respectively. These highly expressed Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in the saliva, alone or in combination, indicate their predictive value for ESCC.

Predictive value of the presence of Prevotella and the ratio of Porphyromonas gingivalis to Prevotella in saliva for esophageal squamous cell carcinoma.

Background: Imbalance of oral salivary microbiota has been linked to the pathogenesis of a variety of systemic diseases, and oral bacterial species have been shown to be useful biomarkers for systemic diseases.This study aimed to characterize the alterations of oral microbiota in patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the diagnostic performance of oral microbial biomarkers for ESCC. Methods: The relative abundance of flora in saliva samples was analyzed by 16S rDNA sequencing, and differences in the species present in samples from ESCC patients and healthy controls (HCs) were identified by analyzing species diversity and performing LEfSe analysis. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of the characteristic bacteria individually and in combination. Results: Differences in bacterial diversity indexes were observed for the saliva of ESCC patients versus HCs (P<0.05), but principal coordinate analysis did not detect a significant difference in the composition of oral microbiota between ESCC patients and HCs (P>0.05). LEfSe analysis showed that Leptotrichia, Porphyromonas (Pg), Streptococcus, Rothia, Lactobacillus and Peptostreptococcus were more abundant in ESCC patient saliva than in HC saliva, whereas Haemophilus, Alloprevotella (All), Prevotella_7, Prevotella (Pre), Prevotella_6, Pasteurellaceae and Pasteurellales were significantly less abundant in ESCC patient saliva (P<0.05). From ROC curve analysis, Pg could detect ESCC with an area under the ROC curve (AUC) of 0.599, sensitivity of 62.2%, and specificity of 70%, whereas the ratio of Pg/Pre had an AUC of 0.791, sensitivity of 93.3%, and specificity of 62.3%. Moreover, the combination of the Pg/Pre and Pg/All ratios showed further improved diagnostic performance for ESCC (AUC=0.826) and even good sensitivity and specificity for the diagnosis of early ESCC (68.2% and 86%, respectively; AUC=0.786). Conclusion: This study shows that Pg in saliva can be used as a characteristic marker of ESCC, and the ratios of Pg/Pre and Pg/All offered significantly improved diagnostic performance, especially for early ESCC.

Prognosis of rectal neuroendocrine tumors after endoscopic resection: a single-center retrospective study.

BACKGROUND: The efficacy of endoscopic resection in patients with rectal neuroendocrine tumors (NETs) which are less than 20 mm in diameter remains unclear. This study aimed to investigate the efficacy and outcomes of different types of endoscopic resection in patients with NETs. METHODS: We performed a retrospective analysis and follow-up on 98 patients who underwent endoscopic resection for rectal NETs between August 2010 and October 2019 at Guangdong Provincial People's Hospital, China. The lesions were preoperatively classified according to their endoscopic morphology and measured by endoscopic ultrasound. Patients were divided into modified endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) groups depending on the endoscopic treatment they received. The en bloc resection rate, histopathological complete resection rate, and the complication rate of the 2 groups were evaluated after the operation. The risk factors for incomplete resection were also analyzed. RESULTS: The average diameter of the 98 NETs was 6.29±2.90 mm (range, 2-15 mm). The en bloc resection rate of the modified EMR and ESD treatment groups was 97.2% (35/36) and 100% (62/62), respectively. The histopathological complete resection rate was 86.1% (31/36) and 87.1% (54/62), respectively. No tumor recurrence or tumor-related death occurred. There were no statistically significant differences in the rate of histopathological complete resection, perforation, or delayed hemorrhage between the 2 groups (P>0.05). Multivariate analysis demonstrated that the depth of tumor invasion (P=0.007) and tumor diameter (P<0.001) were independent risk factors for histopathological complete resection. CONCLUSIONS: Modified EMR and ESD are safe and effective endoscopic approaches for the resection of rectal NETs ≤15 mm in diameter. Endoscopic resection requires a comprehensive preoperative evaluation of risk factors including the depth of tumor invasion and tumor diameter.

Clinical usefulness of gastric adenocarcinoma predictive long intergenic noncoding RNA in human malignancies: A meta-analysis.

BACKGROUND: Gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC), a newly identified lincRNA, was reported to be aberrantly expressed in several kinds of cancers and played an important role in tumor progression. This study was performed to systematically estimate the prognostic role of GAPLINC expression in cancer patients. METHODS: Several electronic databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched for potential literature (updated to September 3, 2018). The pooled hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a fixed effects model using Stata12.0 software. RESULTS: The pooled results indicated that elevated GAPLINC was significantly related to shorter overall survival (OS) (HR = 1.66, 95%CI: 1.40-1.93, p < 0.001), which was further validated using The Cancer Genome Atlas (TCGA) dataset. Furthermore, high GAPLINC expression was correlated with higher tumor grade (OR = 1.91, 95%CI: 1.35-2.70, p < 0.001), positive lymph node metastasis (OR = 2.80, 95%CI: 1.69-4.64, p < 0.001), deeper infiltration depth (OR = 2.44, 95%CI: 1.43-4.17, p = 0.001) and advanced clinical stage (OR = 3.54, 95%CI: 2.13-5.88, p < 0.001). CONCLUSIONS: Our results suggest that elevated GAPLINC was associated with poor clinical outcomes and might serve as a promising prognostic biomarker in cancer survivors.

LncRNA PCAT-1 in gastrointestinal cancers: A meta-analysis.

BACKGROUND: Prostate-cancer-associated ncRNA transcript 1 (PCAT-1), a newly discovered lncRNA, was implicated in the progression of multiple tumors. We conducted a systematic review and meta-analysis to determine its prognostic potential for gastrointestinal cancers. METHODS: A literature survey was conducted by searching the PubMed, Web of Science, Cochrane Library, Embase together with Wanfang, and China National Knowledge Infrastructure (CNKI) database for articles published as of October 15, 2017. Hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (95% CIs) were calculated to demonstrate prognostic value of PCAT-1 using Stata 12.0 software. RESULTS: A total of 6 studies with 961 cases were pooled in the analysis to evaluate the prognostic value of PCAT-1 in gastrointestinal cancers. Increased PCAT-1 expression was significantly correlated with poor overall survival (OS) (HR = 1.04, 95% CI: 1.02-1.06). Statistical significance was also observed in subgroup meta-analysis stratified by cancer type, histology type, sample size, and analysis type. Additionally, high expression of PCAT-1 was significantly associated with deeper tumor invasion (OR = 4.46, 95% CI: 3.00-6.63), positive lymph node metastasis (OR = 3.76, 95% CI: 1.39-10.16), and advanced clinical stage (OR = 4.09, 95% CI: 1.55-10.82). CONCLUSION: High expression of PCAT-1 was related to poor prognosis and could be a promising biomarker of clinicopathologic features in gastrointestinal cancers. More studies will be necessary to verify and strengthen the clinical value of PCAT-1 in gastrointestinal cancers.

Prognostic role of chromodomain helicase DNA binding protein 1-like protein in human solid cancers: A meta-analysis.

BACKGROUND: Chromodomain helicase DNA binding protein 1-like (CHD1L) played vital roles in tumorigenesis and development. Its aberrant expression was reported to be related to progression and prognosis in various tumors. However, no consensus on the prognostic value of CHD1L protein has been made. This meta-analysis was aimed to assess the clinical significance of CHD1L protein in human solid tumors. METHODS: Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were extensively searched to retrieve publications that reported the association between CHD1L expression and cancer prognosis. Hazard ratios (HRs) or odds ratios (ORs) with their 95% confidence intervals (95% CIs) were applied to assess the strength of the associations through Stata statistical software version 12.0 or Revman software 5.3, respectively. RESULT: A total of 14 studies were screened according to the inclusion criteria. The pooled results revealed patients with higher CHD1L expression manifested with decreased overall survival (OS) (HR: 1.59, 95% CI: 1.29-1.89, P < .001) and poorer disease-free survival (DFS) (HR: 1.66, 95% CI: 1.17-2.15, P < .001). The prognostic value of CHD1L protein for OS was further confirmed by performing subgroup meta-analysis. Furthermore, the pooled results revealed a positive correlation of CHD1L protein expression with tumor depth (OR: 1.87, 95% CI: 1.48-2.37), lymph node metastasis (OR: 1.46, 95% CI: 1.01-2.11), and distant metastasis (OR: 1.86, 95% CI: 1.45-2.38). CONCLUSION: CHD1L overexpression was associated with poor prognosis and advanced clinicopathological features, CHD1L may be a valuable biomarker for prognostication of cancer patients.

Prognostic and clinical value of Targeting protein for Xenopus kinesin-like protein 2 in patients with gastrointestinal tract cancers: A meta-analysis.

BACKGROUND: Accumulating studies have indicated that Targeting protein for Xenopus kinesin-like protein 2 (TPX2) was overexpressed in various types of human cancers. However, the prognostic and clinical value of TPX2 in gastrointestinal (GI) tract cancers was not well-understood. This study was aimed to comprehensively explore the prognostic and clinical significance of TPX2 in GI tract cancers. METHODS: Eligible studies were systematically retrieved in PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang database. The eligible studies were collected to evaluate the association of TPX2 with prognosis and clinicopathological features, with the pooling hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI). RESULT: The meta-analysis suggested that overexpression of TPX2 protein was significantly correlated with poor overall survival (OS) (HR: 2.20, 95% CI: 1.60-2.80, P <.001) in GI tract cancers, the subgroup meta-analysis also confirmed the prognostic value of TPX2 protein. Furthermore, clinical significances of TPX2 protein in gastric cancer were discussed. CONCLUSION: Upregulated TPX2 protein was correlated with poor clinical outcomes, suggesting that TPX2 protein can serve as a promising predictive biomarker in patients with GI tract cancers.

Overexpression of Bmi­1 promotes epithelial­mesenchymal transition in CD133+Hep G2 cells.

Cancer stem cells (CSCs) and epithelial­mesenchymal transition (EMT) are critical factors contributing to tumor metastasis and recurrence. The BMI1 proto­oncogene (Bmi­1) promotes the development and progression of hematologic malignancies and of several types of solid tumors. The aim of the present study was to explore the mechanism by which Bmi­1 may promote invasion and migration of hepatocellular carcinoma Hep G2 cells. CD133 antigen is a transmembrane glycoprotein and regarded as a cancer stem cells marker in hepatocellular carcinoma. CD133+Hep G2 cells were enriched by magnetic­activated cell sorting and exhibited greater viability compared with CD133­Hep G2 cells, as measured by Cell Counting kit­8 assay. Then, Bmi­1 was overexpressed in CD133+Hep G2 cells by transfection with the Bmi­1/pcDNA3.1(+) expression plasmid, and overexpression was confirmed by reverse­transcription­polymerase chain reaction and western blotting. Overexpression of Bmi­1in CD133+Hep G2 cells resulted in the downregulation of E­cadherin and upregulation of Vimentin at the protein level. The invasion and migration abilities of CD133+Hep G2 cells were increased in the Bmi­1/pcDNA3.1(+)­transfected group, as measured by Transwell invasion and wound healing assays, respectively. In conclusion, Bmi­1 promoted invasion and migration of CD133+Hep G2 cells most likely through inducing EMT. The present findings may offer a potential novel target for the development of hepatocellular carcinoma therapies.

Overexpression of non­SMC condensin I complex subunit G serves as a promising prognostic marker and therapeutic target for hepatocellular carcinoma.

The non­SMC condensin I complex subunit G (NCAPG) that organizes the coiling topology of individual chromatids, represents an overexpressed antigen in various types of cancer, and also contributes to restructuring chromatin into rod­shaped mitotic chromosomes and ensuring the segregation of sister chromatid during cell division. In this study, we investigated the association between NCAPG expression and the biological behavior of hepatocellular carcinoma (HCC) to further explore the potential of NCAPG as a therapeutic target. The expression of NCAPG was detected in human HCC cell lines and tumor samples. The effects of NCAPG on the cell cycle, apoptosis and metastasis were investigated by various assays. NCAPG was found to be overexpressed in HCC compared with the adjacent normal tissue (P<0.001), and high levels of NCAPG expression were found to significantly correlate with recurrence, the time of recurrence, metastasis, differentiation and TNM stage. Furthermore, an elevated expression of NCAPG was associated with a poor overall survival (P<0.05). In addition, in vitro experiments further confirmed the ex vivo data; i.e., the knockdown of NCAPG expression reduced HCC cell viability, but induced apoptosis and arrested the cells at the S phase of the cell cycle. The knockdown of NCAPG expression also inhibited tumor cell migration and the cell invasive capacity in vitro. At the protein level, the knockdown of NCAPG expression upregulated Bax, cleaved caspase­3 and E­cadherin, but downregulated cyclin A1, CDK2, Bcl­2, N­cadherin and HOXB9 expression, suggesting that the knockdown of NCAPG expression suppressed tumor cell epithelial­mesenchymal transition. On the whole, this study demonstrates that NCAPG plays an important role in the development and progression of HCC, and that it may be a novel therapeutic target for patients with HCC.

Positive association between IL-16 rs1131445 polymorphism and cancer risk: a meta-analysis.

INTRODUCTION: The association between IL-16 rs1131445 polymorphism and cancer risk is not consistent or even contradictory, this meta-analysis aims to investigate the role of IL-16 gene rs1131445 polymorphisms in the risk of cancer. EVIDENCE ACQUISITION: A comprehensive online search was conducted in PubMed, EMBASE and CNKI databases to identify eligible studies. The case-control studies related IL-16 rs1131445 C/T polymorphism with the cancer susceptibility were selected according to the inclusion and exclusion criteria. After extracting the basic data information and quality of literature evaluation, the meta-analysis was performed by using STATA 12.0 software, with calculating odds ratio and 95% confidence interval, and further subgroup analysis, literature publication bias test and sensitivity analysis. EVIDENCE SYNTHESIS: There are totally 1677 cases and 1989 non-tumor controls finally involved. Meta-analysis showed that there are statistical correlations between the IL-16 rs1131445 C/T polymorphism and the cancer risk in Asian populations (TS vs. C, OR=0.80, 95%CI: 0.73-0.88; TT vs. TC, OR=0.75, 95%CI: 0.65-0.87; TT vs. CC, OR=0.69, 95% CI: 0.56-0.84; CC+TC vs. TT, OR=1.36, 95%CI: 1.19-1.55; CC vs. TC+TT, OR=1.27, 95%CI: 1.05-1.53) (all P<0.05). CONCLUSIONS: IL-16 rs1131445 C/T polymorphism is related to the susceptibility to cancer in Asians, suggesting that the C allelic gene of rs1131445 is significantly associated with an increasing cancer risk.

MiR-21/RASA1 axis affects malignancy of colon cancer cells via RAS pathways.

AIM: To determine how the oncogene miR-21 regulates the RAS signaling pathways and affects colon cancer cell behaviors. METHODS: RAS p21 GTPase activating protein 1 (RASA1) protein expression in six colon cancer cell lines was assessed by Western blot. Colon cancer RKO cells were chosen for transfection because they are KRAS wild type colon cancer cells whose RASA1 expression is significantly decreased. RKO cells were transfected with vectors overexpressing or down-regulating either miR-21 or RASA1. Furthermore, a luciferase reporter assay was used to determine whether RASA1 is a gene target of miR-21. Then, changes in mRNA and protein levels of RASA1, RAS-GTP, and other components of the RAS signaling pathways were assessed in transfected RKO cells by real-time quantitative reverse transcription-polymerase chain reaction, Western blot and immunoprecipitation. Finally, cell proliferation, apoptosis, invasion, and tumor formation ability were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye assay, flow cytometry, transwell assay, and animal experiment, respectively. RESULTS: RASA1 protein levels were significantly decreased in RKO cells compared with the other 5 colon cancer cell lines, and RASA1 was confirmed as a target gene of miR-21. Interestingly, RASA1 mRNA and protein levels in pre-miR-21-LV (up-regulation of miR-21) cells were lower than those in anti-miR-21-LV (down-regulation of miR-21) cells (P < 0.05). In addition, pre-miR-21-LV or siRASA1 (down-regulation of RASA1) cells showed higher cell proliferation, reduced apoptosis, increased expression of RAS-GTP, p-AKT, Raf-1, KRAS, and p-ERK1/2, and higher invasion and tumor formation ability, compared with control, anti-miR-21-LV or pcDNA3.1-RASA1 (up-regulation of RASA1) cells (P < 0.05). CONCLUSION: RASA1 is a target gene of miR-21, which promotes malignant behaviors of RKO cells through regulation of RASA1 expression.