Hongjia Li

Hypoxia-induced vasculogenic mimicry formation in human colorectal cancer cells: Involvement of HIF-1a, Claudin-4, and E-cadherin and Vimentin

Vasculogenic mimicry (VM) plays an important role in colorectal cancer (CRC) metastasis, and both hypoxia and the epithelial-mesenchymal transition (EMT) are necessary for VM. In this study, HIF-1α expression was upregulated in the VM-positive CRC cell line HCT-116 and thereby affected the expression of the EMT-related markers Claudin-4, E-cadherin (E-cd) and Vimentin(VIM). SB431542 and U0126EtOH, which can inhibit of EMT were used to treat HCT-116 and HCT-8 in these experiments. Both of the inhibitors had significant effect on EMT markers and the formations of VM in CRC cells. In addition, knockdown of HIF-1α in the HCT-116 cells inhibited their capacity for VM. Our study reveals a regulatory role for HIF-1α in VM and suggests that targeting either HIF-1α or EMT may be a valuable strategy for the elimination of CRC metastasis.

Prognostic significance of VEGF-C immunohistochemical expression in colorectal cancer: A meta-analysis

BACKGROUND We sought to comprehensively summarize available evidence for the use of VEGF-C protein to evaluate the clinicopathological and prognostic role of VEGF-C in colorectal cancer. METHODS Electronic databases from inception to February 2016 were used to search without language restrictions for original articles. A meta-analysis was undertaken to assess the relationship between VEGF-C expression and overall survival (OS) in colorectal cancer. RESULTS Twenty-seven studies were included in the final meta-analysis. We aggregated 13 trials (n=1.428 patients) that evaluated the correlation between OS and VEGF-C overexpression. Statistics were performed for OS (HR=1.95; 95%CI=1.31-2.92, P=0.007). When the studies were stratified by the pathological variables, including T stage (n=383 patients; OR=1.79; 95%CI=1.14-2.81), lymph node metastasis (n=3212 patients; OR=4.21; 95%CI=3.49-5.08), M stage (n=1106 patients; OR=4.46; 95%CI=2.96-6.70), vascular invasion(n=1471 patients; OR=2.18; 95%CI=1.65-2.88), lymph invasion (n=831 patients; OR=3.95; 95%CI=2.80-5.56), histo-differentiation (n=1695 patients; OR=1.34; 95%CI=1.00-1.79) and Dukes stage(n=778 patients; OR=4.90; 95%CI=3.55-6.75), TNM stage (n=808 patients; OR=1.73; 95%CI=1.18-2.54) provided critical and comprehensive prognostic information. CONCLUSION Our results demonstrated that VEGF-C overexpression was associated with OS in colorectal cancer.

Exploring the medication duration based on the effect of traditional Chinese medicine on postoperative stage I-III colorectal patients: a retrospective cohort study

Purpose To clarify the effect of tradional Chinese medicine (TCM) on different stage patients and to explore medication duration based on survival analysis. Results 523 and 294 patients were respectively in the TCM group and the control group. For all patients, 6-year disease-free survival (DFS) was 57.6% after TCM and 46.6% after non-TCM (p = 0.0006). 6-year DFS for patients with stage I disease in the TCM group was 79.5% compared with 89.1% in the control group (p = 0.65). For patients with stage II disease, 6-year DFS was 63.1% in the TCM group compared with 50.2% in the control group (p = 0.054), and for patients with stage III disease, it was 43.3% in the TCM group compared with 22.0% in the control group (p = 0.0000). Materials and Methods Data for patients with stage I-III disease between 2004 and 2013 were retrieved for this study, who underwent TCM after surgery were in the TCM group and the others were in the control group. Clinic appointments or phone were used to collect data by research assistants. Survival data were collected on Nov 2015 from the database, which is continuously updated by the researchers. Conclusions TCM is associated with significantly improved disease-free survival, in particular for patients with stage III disease. Among of these, TCM is not necessary for patients with stage I disease, and postoperative patients with stage II disease should be recommended to take 2 years of TCM. For patients with stage III disease, adherence to medication of TCM during the 6-year follow-up is worthy of being recommended.

Is Ep-CAM Expression a Diagnostic and Prognostic Biomarker for Colorectal Cancer? A Systematic Meta-Analysis

Background Cancer stem cell (CSC) epithelial cell adhesion molecule (Ep-CAM) is frequently expressed in colorectal cancer (CRC). However, the clinical significance of Ep-CAM expression in CRC is not clear. This study evaluated whether Ep-CAM provided valuable insight as a molecular biomarker for CRC diagnosis and prognosis and the potential of Ep-CAM as a novel therapeutic target in CRC. Methods Publications were selected online using electronic databases. The pooled odds ratios (ORs) or hazard ratios (HRs) with their 95% confidence intervals (95% CIs), and the combined sensitivity, specificity, and area under the curve (AUC) were calculated and summarized. Results Eleven eligible articles published in English involving 4561 cases were analyzed in this study. Ep-CAM expression was significantly higher in CRC compared with normal controls, and its overexpression was negatively linked to tumor differentiation, tumor stage, vascular invasion, depth of tumor invasion, lymph node metastasis, distant metastasis, and tumor budding in CRC patients. The loss of Ep-CAM expression positively correlated with these characteristics. Multivariate analysis of loss of Ep-CAM expression correlated with a poor prognosis in disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). The pooled sensitivity, specificity and AUC values of Ep-CAM expression in patients with CRC vs. normal controls were 0.93, 0.90, and 0.94, respectively. Conclusions The present findings suggest that Ep-CAM expression may be associated with CRC carcinogenesis, while the loss of Ep-CAM expression is correlated with the progression, metastasis, and poor prognosis of CRC. Ep-CAM expression may be a useful biomarker for the clinical diagnosis of CRC.

Prevention of cisplatin-based chemotherapy-induced delayed nausea and vomiting using triple antiemetic regimens: a mixed treatment comparison

A variety of triple antiemetic regimens are being used to prevent cisplatin-based chemotherapy induced delayed emesis and nausea in cancer patients. We performed a network meta-analysis to compare the efficacies of the different regimens. Electronic searches of the PubMed, Cochrane Library and MEDLINE databases were performed to identify randomized controlled trials, and data were analyzed using JAGS, Stata 14.0 and R project. The primary outcome was a complete response (CR). The secondary outcomes were no vomiting (NV) and no nausea (NN). Among the 398 studies identified, 10 were eligible and included, providing data on nine regimens. In the CR analysis, the absolute rank of netupitant + palonosetron + dexamethasone (NEPA) was 0.8579. In the NV and NN analyses, NEPAs absolute ranks were 0.8631 and 0.7902, respectively. The compliance of patients treated with rolapitant + granisetron + dexamethasone (RGD) was the best due to a low incidence of adverse events, and good compliance was also observed with NEPA. It was difficult to achieve good compliance with aprepitant + granisetron + dexamethasone (AGD). Overall, NEPA was the best regimen, and aprepitant + ondansetron + dexamethasone (AOD) is also worthy of recommendation because of its low cost and good effect. For patients with severe constipation, hiccups, asthenia and/or delayed nausea, RGD is worthy of consideration.

Clinicopathological, prognostic and predictive value of CD166 expression in colorectal cancer: a meta-analysis

CD166 has been identified as an important cancer stem cell (CSC) marker in colorectal cancer (CRC). The purpose of our study was to investigate the relationship between CD166 expression and clinical features and to examine the role of CD166 expression on the survival of patients with CRC. A total of 15 studies with 3,332 cases were identified in this meta-analysis. The pooled OR indicated that CD166 expression was significantly higher in CRC than in colonic adenomas or normal colonic mucosa (OR = 3.48, P = 0.002 and OR = 55.13, P = 0.017, respectively). CD166 expression was found to be negatively correlated with vascular invasion (OR = 0.75, P = 0.017), but it was not associated with gender, tumor location, lymph node status, distant metastasis, clinical stage, T classification or tumor differentiation. Meanwhile, CD166 expression was not associated with the prognosis of overall survival (OS) (HR = 1.20, 95% CI = 0.45-3.22, P = 0.72) in multivariate regression analysis. One study reported that CD166 expression may be a predictor of survival in stage II CRC patients using multivariate logistic regression analysis (OS: OR = 9.97, P = 0.035; disease-specific survival: OR = 29.02, P = 0.011). Our findings suggest that CD166 expression may be correlated with CRC carcinogenesis and a decreased risk of vascular invasion, and it may become a predictive biomarker of survival for stage II CRC patients, but additional studies with large sample sizes are essential to validate the prognostic and predictive values of CD166 expression.CD166 has been identified as an important cancer stem cell (CSC) marker in colorectal cancer (CRC). The purpose of our study was to investigate the relationship between CD166 expression and clinical features and to examine the role of CD166 expression on the survival of patients with CRC. A total of 15 studies with 3,332 cases were identified in this meta-analysis. The pooled OR indicated that CD166 expression was significantly higher in CRC than in colonic adenomas or normal colonic mucosa (OR = 3.48, P = 0.002 and OR = 55.13, P = 0.017, respectively). CD166 expression was found to be negatively correlated with vascular invasion (OR = 0.75, P = 0.017), but it was not associated with gender, tumor location, lymph node status, distant metastasis, clinical stage, T classification or tumor differentiation. Meanwhile, CD166 expression was not associated with the prognosis of overall survival (OS) (HR = 1.20, 95% CI = 0.45-3.22, P = 0.72) in multivariate regression analysis. One study reported that CD166 expression may be a predictor of survival in stage II CRC patients using multivariate logistic regression analysis (OS: OR = 9.97, P = 0.035; disease-specific survival: OR = 29.02, P = 0.011). Our findings suggest that CD166 expression may be correlated with CRC carcinogenesis and a decreased risk of vascular invasion, and it may become a predictive biomarker of survival for stage II CRC patients, but additional studies with large sample sizes are essential to validate the prognostic and predictive values of CD166 expression.

Association Between Hypoxia-Inducible Factor-2α (HIF-2α) Expression and Colorectal Cancer and Its Prognostic Role: a Systematic Analysis

Background/Aims: Although some studies showed that HIF-2α expression was correlated with an unfavorable prognosis in colorectal cancer (CRC), the prognostic results remain conflicting in CRC. The present study was performed to evaluate the association between HIF-2α expression and the clinicopathological features of this disease and to examine the potential prognostic role of HIF-2α expression in CRC. Methods: Pooled odds ratios (ORs) or hazard ratios (HRs) were calculated from available publications, The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Trial sequential analysis (TSA) was used to estimate the required sample information. Results: HIF-2α protein expression was more frequent in CRC than in normal colonic tissues (OR = 150.49, P < 0.001), higher in male than female CRC patients (OR = 1.47, P = 0.008), and lower in high-grade than low-grade CRC (OR = 0.49, P = 0.029). TSA verified the reliability of the above results. HIF-2α expression was not linked to the prognosis of CRC in overall survival (OS), disease-specific survival (DSS), metastasis-free survival, and relapse-free survival, and no significant correlation was found between HIF-2α alteration and OS or disease-free survival (DFS) of CRC. Expression of both HIF-2α and vascular endothelial growth factor (VEGFA, VEGFB, or VEGFC) was associated with a poor metastasis-free survival of CRC (HR = 6.95, HR = 113.51, and HR = 8.11, respectively). No association was observed between HIF-2α expression and DFS in other cancers, but HIF-2α expression was correlated with a worse DFS of CRC (HR = 1.23, P = 0.037). Moreover, HIF-2α expression was linked to a good survival benefit in some cancers (B-cell lymphoma and lung adenocarcinoma: OS, multiple myeloma: DSS, breast cancer: distant metastasis-free survival, liposarcoma: distant recurrence-free survival) (all HRs < 1, Ps < 0.05). Conclusions: HIF-2α expression may be associated with the carcinogenesis of CRC, which is higher in males than in females, negatively linked to tumor differentiation, and correlated with a worse DFS of CRC. Additional prospective studies are needed.

Right- and left-sided colorectal cancers respond differently to traditional Chinese medicine

AIM To explore the differences in the responses of left-sided colorectal cancer (LSCRC) and right-sided colon cancer (RSCC) to traditional Chinese medicine (TCM). METHODS Patients with postoperative stage I-III colorectal cancer (CRC) were enrolled and divided into the LSCRC with or without TCM and RSCC with or without TCM groups depending on the primary tumor side and TCM administration. Patients in the TCM group were given TCM for at least 6 mo. Our research adopted disease-free survival (DFS) as the primary endpoint. We applied a Cox proportional hazards regression model for the multivariate factor analysis using Stata 12.0 and SPSS 22.0 software for data analysis. RESULTS Of the 817 patients included in our study, 617 had LSCRC (TCM group, n = 404; Non-TCM group, n = 213), and 200 had RSCC (TCM group, n = 132; Non-TCM group, n = 68). The 6-year DFS for patients with LSCRC was 56.95% in the TCM group and 41.50% in the Non-TCM group (P = 0.000). For patients with RSCC, the 6-year DFS was 52.92% in the TCM group and 37.19% in the Non-TCM group (P = 0.003). Differences between LSCRC and RSCC were not statistically significant regardless of TCM ingestion. CONCLUSION Patients with either LSCRC or RSCC and who took TCM experienced longer DFS; furthermore, patients with RSCC benefited more from TCM in DFS.