HOXD10, a key regulator of cell-differentiated phenotype maintainence, has been demonstrated to be involved in the tumorigenesis of many human malignacies. However, the status of HOXD10 expression and its biological function in cholangiocellular carcinoma (CCC) remain to be clarified. In the present study, we investigated the clinical significance and biological functions of HOXD10 in CCC and found that the expression of HOXD10 and its downstream effector RHOC was significantly different in well-differentiated CCC tissues compared with poorly-differentiated lesions. We also observed a significant correlation between low HOXD10 and high RHOC expression levels and worse prognosis. The stable overexpression of HOXD10 by lentivirus vector significantly inhibited cell invasion partly by downregulating the expression of MMP2 and MMP9, and significantly increased early apoptosis in CCC cell lines and induced G1 phase cell cycle arrest, contributing to the inhibition of cell proliferation in vitro. Additionally, we demonstrated that the inactivation of the RHOC/AKT/MAPK pathway was involved in the tumor-suppressive functions of HOXD10 in CCC. These results suggested that HOXD10 may be a putative suppressor gene and can act as a prognostic marker and potentially a novel therapeutic target for CCC.

Background: It has been reported that the encapsulated miRNAs from exosomes are potential biomarkers of tumors prognosis. Yet, the results are controversial, so it is obliged to do a meta-analysis to reach a definite conclusion. Materials and methods: Studies were searched for published in PubMed, Embase, and Web of Science databases until April 20, 2018. A meta-analysis was conducted to appraise the role of exosomal miRNAs in prognosis of cancer patients. Results: The different exosomal miRNAs expression was remarkably related to overall survival (OS) (hazard ratio [HR] = 2.02, 95% confidence interval [CI]: 1.84–2.21) and disease-free survival (DFS) (HR = 2.43, 95% CI: 1.86–3.17) of cancer patients. High exosomal miR-21 expression was associated with poor OS (HR = 2.59; 95% CI: 1.71–3.90) and DFS (HR = 1.84; 95% CI: 1.37–2.47). High exosomal miR-451a expression was associated with poor OS (HR = 4.81; 95% CI: 2.33–9.93) and DFS (HR = 2.64; 95% CI: 1.62–4.31). High exosomal miR-1290 expression was associated with poor OS (HR = 1.73; 95% CI: 1.29–2.33). Low exosomal miR-638 expression was associated with poor OS (HR = 2.25; 95% CI: 1.46–3.46). Conclusion: The expression levels of exosomal miRNAs, particularly miR-21, miR-451a, miR-1290, and miR-638 could strongly predict prognosis of solid tumor patients and might be a potential target for tumor treatment.

Ras homolog family member C (RHOC) is important during the progression of several types of cancer, including prostate, breast and hepatocellular carcinoma. However, the function of RHOC in cholangiocellular carcinoma (CCC), a highly recurrent and metastatic carcinoma with poor prognosis, remains unclear. The aim of the present study was to investigate the involvement of RHOC in CCC tumor progression. RHOC expression levels were examined in CCC tissues and cells, and adjacent nontumorous bile duct tissues. The effects and molecular mechanisms of RHOC expression on cell migration and invasion were also investigated. The current study demonstrated that RHOC protein was frequently overexpressed in human CCC specimens and CCC cell lines. Downregulation of RHOC inhibited CCC cell invasion and migration partially via inhibition of matrix metalloproteinase 2, 3 and 9 expression. RHOC also modulated the expression of several epithelial-mesenchymal transition (EMT)-associated proteins, including E‑cadherin, vimentin, Slug and Snail, to promote to EMT progression. The present results demonstrated that RHOC is important for the invasion and migration of CCC through simultaneous regulation of MMPs and EMT‑associated protein, suggesting that RHOC is a potential molecular target for CCC treatment.

BackgroundSome researchers reported that pleiotrophin (PTN) is associated with the development and metastasis of various tumors and it is a poor prognostic factor for the tumor patients. However, the results of other researches are inconsistent with them. It is obliged to do a meta-analysis to reach a definite conclusion.MethodsThe published studies relevant to PTN were searched in the databases including PubMed, Embase and Web of Science until March 20, 2018. A meta-analysis was conducted to evaluate the role of PTN in clinicopathological characteristics and overall survival (OS) of cancer patients.ResultsOur meta-analysis indicated that the high expression of PTN was remarkably associated with advanced TNM stage (OR = 2.79, 95%CI: 1.92–4.06, P<0.00001) and poor OS (HR = 1.77, 95%CI: 1.41–2.22, P<0.00001) in tumor patients. The expression of PTN was not associated with tumor size (OR = 1.12, 95% CI: 0.55–2.26, P = 0.76), lymph node metastasis (LNM) (OR = 1.95, 95%CI: 0.62–6.12, P = 0.25), distant metastasis (DM) (OR = 2.78, 95%CI: 0.72–10.74, P = 0.14) and histological grade (OR = 1.95, 95%CI: 0.98–3.87, P = 0.06).ConclusionThe high expression of PTN is significantly relevant to the advanced TNM stage and poor OS in tumor patients. PTN can serve as a promising biomarker to predict unfavorable survival outcomes, and it may be a potential target for tumor treatment.

Background SHP2 is a latent biomarker for predicting the survivals of solid tumors. However, the current researches were controversial. Therefore, a meta-analysis is necessary to assess the prognosis of SHP2 on tumor patients. Materials and methods Searched in PubMed, EMBASE and web of science databases for published studies until Jun 20, 2021. A meta-analysis was performed to evaluate the affect of SHP2 in clinical stages, disease-free survival (DFS) and overall survival (OS) in tumor patients. Results This study showed that the expression of SHP2 had no significant correlation with clinical stages (OR: 0.91; 95% CI, 0.60–1.38; P = 0.65), DFS (HR = 0.88; 95%CI: 0.58–1.34; P = 0.56) and OS (HR = 1.07, 95%CI: 0.79–1.45, P = 0.67), but the prognostic effect varied greatly with tumor sites. High SHP2 expression was positively related to early clinical stage in hepatocellular carcinoma, not associated with clinical stage in the most of solid tumors, containing laryngeal carcinoma, pancreatic carcinoma and gastric carcinoma, etc. Higher expression of SHP2 could predict longer DFS in colorectal carcinoma, while predict shorter DFS in hepatocellular carcinoma. No significant difference was observed in DFS for non-small cell lung carcinoma and thyroid carcinoma. Higher SHP2 expression was distinctly related to shorter OS in pancreatic carcinoma and laryngeal carcinoma. The OS of the other solid tumors was not significantly different. Conclusions The prognostic value of SHP2 might not equivalent in different tumors. The prognostic effect of SHP2 is highly influenced by tumor sites.

Eligible studies were searched in Cochrane library, Pubmed, Medline, CBM, CNKI and VIP databases from establishment to June 2014. Two researchers independently identified 7 randomized controlled trials (RCTs) and extracted data of Brucea javanica oil emulsion injection combined with chemotherapy. Based on the published studies, the researchers analyzed them by RevMan 5.2 software and investigated the efficacy and safety of Brucea javanica oil emulsion injection combined with chemotherapy for patients with advanced gastric cancer by Meta analysis. Meta analysis showed that, compared with the simple chemotherapy, Brucea javanica oil emulsion injection combined with chemotherapy could increase objective response rate by 43%(RR=1.43, P<0.001). In addition, the incidence of neutropenia (RR=0.56, P<0.001), thrombocytopenia (RR=0.64, P=0.02), nausea, vomit (RR=0.66, P=0.002) decreased in these patients. However, the quality of life was not improved significantly in gastric carcinoma patients with combined therapy (RR=1.36, P=0.07). The paper suggested Brucea javanica oil emulsion injection combined with chemotherapy could increase efficacy and safety, which might be a promising therapy for patients with advanced gastric cancer.

This study was conducted to investigate survival and prognostic factors for extrahepatic cholangiocarcinoma (ECC) following surgical resection and evaluate the effects of postoperative adjuvant therapy (AT) on overall survival (OS). We retrospectively collected clinical and pathological data between March, 2008 and December, 2013. The Kaplan-Meier method and the COX regression model were used to evaluate the OS and prognostic factors of 105 postoperative ECC patients, of whom 32 had received AT. The patients were stratified into seven risk subgroups and the survival rates were compared within each subgroup between patients who received AT and those who did not. The results demonstrated a median OS of 17.6 months, with 1- and 3-year survival rates of 67.9 and 19.5%, respectively, for the entire cohort. On univariate analysis, preoperative cholangitis, non-R0 surgical margins, poor differentiation grade, stage 3/4 and lymphatic metastasis were identified as adverse prognostic factors. AT was not significantly associated with improved OS. However, the subgroup analysis revealed that the effect of AT was significant only in the lymphatic metastasis group (median OS, 21.6 vs. 10.4 months; and 3-year OS, 16.6 vs. 0%, respectively; P=0.02). The survival curves of the AT and non-AT groups were significantly different only for node-positive patients. The COX regression model identified lymphatic metastasis, surgical margins and AT as independent prognostic factors for ECC. A negative resection margin may reduce the mortality rate following surgery by 47%. By contrast, lymph node metastasis was associated with a 2.18-fold higher mortality rate for ECC patients. Postoperative AT contributed to a 0.45-fold mortality rate compared to non-AT ECC patients. Therefore, we concluded that AT is a favorable prognostic factor for ECC patients and it may prolong the survival of patients with lymphatic metastasis. Our data suggest that postoperative AT should be recommended for node-positive ECC patients.

Most of pleural effusions are caused by tuberculosis and malignant tumor. Difficult sampling and bacterial sparing nature of these diseases challenge doctors’ diagnosis in China. This study aimed to develop a new convenient and effective method for the differentiation of tuberculous and malignant pleural effusion. A prospective cohort study of patients hospitalized with malignant (n = 90) and tuberculous (n = 130) pleural effusions from September 2018 to October 2020 was performed. The diagnostic performance of the age to pleural fluid ADA ratio (age/ADA) and other indicators to distinguish tuberculous and malignant pleural effusions was evaluated by receiver operating characteristic (ROC) curve analysis. The areas under the curve (AUC) of age/ADA and pleural fluid ADA were largest. Age/ADA showed sensitivity and specificity of 81.5% (95%CI 73.8%–87.8%) and 97.8% (95%CI 92.2%–99.7%) respectively. The sensitivity and specificity of pleural fluid ADA were 83.1% (95%CI 75.5%–89.1%) and 93.3% (95%CI 86.1%–97.5%) respectively. The positive likelihood [36.69 (95%CI 9.3–144.8)] of age/ADA was significantly higher than that of pleural fluid ADA [12.46 (95%CI 5.7–27.1)]. The AUCs for Cancer Ratio and Cancer Ratio plus were lower and showed a sensitivity of 80.0% (95%CI 72.1%–86.5%), 80.0% (95%CI 70.2%–87.7%) and a specificity of 81.5% (95%CI 73.8%–87.8%), 80.0% (95%CI 70.2%–87.7%) respectively. Age/ADA has a higher diagnostic accuracy than ADA. Age/ADA is a promising diagnostic index for tuberculous and malignant pleural effusion with high sensitivity and specificity, especially the high positive likelihood ratio. The diagnostic accuracy of Cancer Ratio and Cancer Ratio plus are inferior to those of age/ADA and ADA.