Dajing Xia

Aspirin use after diagnosis but not prediagnosis improves established colorectal cancer survival: a meta-analysis

Objective The objective of this meta-analysis was to systematically assess the survival benefit of aspirin use before or after diagnosis for patients with colorectal cancer (CRC). Design Relevant studies were identified through searching PubMed, Embase and Cochrane databases before May 2014. Two investigators extracted data independently for baseline characteristics and outcomes from the included studies. Either a fixed-effects or a random-effects model was derived to composite the pooled HR for overall mortality and CRC-specific mortality of CRC. Results Seven studies on postdiagnosis aspirin therapy and seven studies on prediagnosis aspirin use were finally included in this meta-analysis. The overall survival benefit associated with postdiagnosis aspirin use represented an HR of 0.84 (95% CI 0.75 to 0.94). This effect was observed both in colon cancer (HR=0.78, 95% CI 0.64 to 0.96) and in rectal cancer (HR=0.90, 95% CI 0.83 to 0.98). Besides, the survival benefit of postdiagnosis aspirin use appeared to be confined to those patients with positive prostaglandin endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase-2, COX-2) expression (HR=0.65, 95% CI 0.50 to 0.85) and with mutated PIK3CA tumours (HR=0.58, 95% CI 0.37 to 0.90). Aspirin use postdiagnosis was not associated with CRC-specific mortality (HR=0.77, 95% CI 0.52 to 1.14). We observed no evidence of an association between prediagnosis aspirin use and CRC overall mortality (HR=1.01, 95% CI 0.96 to 1.06) or CRC-specific mortality (HR=0.93, 95% CI 0.82 to 1.05). Conclusions These findings provide further indication that postdiagnosis aspirin therapy improved CRC overall survival, especially for patients with positive PTGS2 (COX-2) expression and mutated PIK3CA tumours.

Importance of ROS-mediated autophagy in determining apoptotic cell death induced by physapubescin B

Physapubescin B, a steroidal compound extracted from the plant Physalis pubescens L. (Solanaceae), has been reported to possess anti-cancer potential, whereas the molecular mechanism remains elusive. In this study, we first demonstrated that physapubescin B induced autophagy in human cancer cells based on the evidence that physapubescin B increased lipidation of microtubule-associated protein 1 light chain 3 (LC3) as well as number of GFP-LC3 puncta. We further examined the molecular mechanisms and found that physapubescin B enhanced the autophagic flux through promotion of reactive oxygen species (ROS)-mediated suppression of mammalian target of rapamycin complex I (mTORC1), the key negative regulator of autophagy. Additionally, excessive ROS caused by physapubescin B also induced p53-dependent apoptotic cell death. Furthermore, we provided evidence that inhibition of autophagy either by a chemical inhibitor or gene silencing promoted physapubescin B-induced apoptotic cell death, indicating that autophagy serves as a cell survival mechanism to protect cell death. Thus, our data provide a clue that inhibition of autophagy would serve as a novel strategy for enhancing the anti-cancer potential of physapubescin B.

Diagnostic and Prognostic Value of Serum Interleukin-6 in Colorectal Cancer.

AbstractThe application of serum interleukin-6 (IL-6) in the diagnosis and prognosis of colorectal cancer (CRC) has been evaluated in many studies, whereas the results were contradictive.The aim of this study was to systematically evaluate this issue.An original study was conducted to explore the diagnostic value of serum IL-6 in CRC. Pubmed, Embase, and Cochrane library databases were searched for eligible studies.For diagnostic meta-analysis, aggregate data (AD) and individual participant data (IPD) meta-analyses were both adopted. The sensitivity and specificity were pooled and a summary receiver-operating characteristic (ROC) curve was constructed. For prognostic meta-analysis, study-specific hazard ratios (HRs) of IL-6 for survival were summarized. Secondary analysis of survival data was performed to synthesize the Kaplan–Meier curves.Total 17 studies (including our study) were included in this meta-analysis. The pooled sensitivity, specificity, and area under curve (AUC) of serum IL-6 were 0.72 (95% CI: 0.46–0.88), 0.74 (95% CI: 0.56–0.86), and 0.79 (95% CI: 0.75–0.82) in CRC diagnosis, respectively. Further, IPD meta-analysis strengthened the diagnostic value of serum IL-6 (the AUC, sensitivity, and specificity were 0.794, 0.606, and 0.839, respectively). For prognostic analysis, the high serum level of IL-6 was inversely associated with overall survival (OS) (pooled HR = 1.76, 95% CI: 1.42–2.19, P < 0.001) and disease-free survival (DFS) (pooled HR = 2.97, 95% CI: 1.76–5.01, P < 0.001). The synthesized Kaplan–Meier curves indicated that CRC patients with higher serum IL-6 level had a worse OS (P = 0.0027) and DFS (P < 0.001), which further support the prognostic value of serum IL-6 in CRC patients.The present study confirmed that serum IL-6 may be a potential biomarker for CRC diagnosis, and the high serum IL-6 level was associated with poor prognosis for both CRC overall survival and disease-free survival.The study has been registered in an international registry of systematic reviews PROSPERO (CRD42013006485).

Association between markers of glucose metabolism and risk of colorectal cancer

Objectives Independent epidemiological studies have evaluated the association between markers of glucose metabolism (including fasting glucose, fasting insulin, homeostasis model of risk assessment-insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c) and C peptide) and the risk of colorectal cancer (CRC). However, such associations have not been systematically analysed and no clear conclusions have been drawn. Therefore, we addressed this issue using a meta-analysis approach. Design Systematic review and meta-analysis. Data sources PubMed and EMBASE were searched up to May 2015. Primary and secondary outcome measures Either a fixed-effects or random-effects model was adopted to estimate overall ORs for the association between markers of glucose metabolism and the risk of CRC. In addition, dose–response, meta-regression, subgroup and publication bias analyses were conducted. Results 35 studies involving 25 566 patients and 5 706 361 participants were included. Higher levels of fasting glucose, fasting insulin, HOMA-IR, HbA1c and C peptide were all significantly associated with increased risk of CRC (fasting glucose, pooled OR=1.12, 95% CI 1.06 to 1.18; fasting insulin, pooled OR=1.42, 95% CI 1.19 to 1.69; HOMA-IR, pooled OR=1.47, 95% CI 1.24 to 1.74; HbA1c, pooled OR=1.22, 95% CI 1.02 to 1.47 (with borderline significance); C peptide, pooled OR=1.27, 95% CI 1.08 to 1.49). Subgroup analysis suggested that a higher HOMA-IR value was significantly associated with CRC risk in all subgroups, including gender, study design and geographic region. For the relative long-term markers, the association was significant for HbA1c in case–control studies, while C peptide was significantly associated with CRC risk in both the male group and colon cancer. Conclusions The real-time composite index HOMA-IR is a better indicator for CRC risk than are fasting glucose and fasting insulin. The relative long-term markers, HbA1c and C peptide, are also valid predictors for CRC risk. Considering the included case–control studies in the current analysis, more cohort studies are warranted to enhance future analysis.

Diagnostic and Prognostic Value of microRNA-21 in Colorectal Cancer: An Original Study and Individual Participant Data Meta-analysis

Background: We aimed to systematically summarize the diagnostic and prognostic value of circulating/tissue miR21 in patients with colorectal cancer. Methods: An original study was conducted to explore the potential value of circulating miR21 in colorectal cancer diagnosis and tissue miR21 in colorectal cancer prognosis. PUBMED and EMBASE were searched (to August, 2013) to identify eligible studies. To explore the diagnostic performance of circulating miR21, meta-analysis methods were used to pool sensitivity, specificity, positive and negative likelihood ratio, diagnostic OR and to construct a summary ROC curve. For prognostic meta-analysis, study-specific HRs of tissue miR21 for survival were summarized. Subgroup and sensitivity analyses were applied to explore heterogeneity. Results: Finally, 14 studies (including our study) were included in the meta-analyses. The pooled sensitivity, specificity, and AUC of circulating miR21 were 0.76 [95% confidence interval (CI), 0.59–0.88], 0.81 (95% CI, 0.76–0.85), and 0.81 (95% CI, 0.78–0.85) in diagnosing colorectal cancer. Patients with higher expression of tissue miR21 had significant inferior overall survival (OS; pooled HR, 1.56; 95% CI, 1.16–2.11) and disease-free survival (DFS; pooled HR, 1.35; 95% CI, 1.08–1.69). The individual participant data (IPD) meta-analysis demonstrated that tissue miR21 level was independently associated with worse colorectal cancer OS (HR, 1.69; 95% CI, 1.07–2.67; P = 0.023), whereas this association seems to be confined to males (P = 0.007) but not for females (P = 0.845). Conclusions: Circulating miR21 level has potential value for colorectal cancer early detection, whereas high tissue miR21 level is associated with adverse colorectal cancer prognosis. Impact: miR21 is a promising biomarker for early detection and prognosis of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 23(12); 2783–92. ©2014 AACR.

Prognostic significance of ZEB1 and ZEB2 in digestive cancers: a cohort-based analysis and secondary analysis

Background Digestive cancers are common malignancies worldwide, however there are few effective prognostic markers available. In this study we comprehensively investigated the prognostic significance of ZEB1 and ZEB2 in digestive cancers. Methods Electronic databases were searched and studies met the selection criteria were included. Study information was recorded and quality assessment was performed according to the REMARK guideline. Hazard ratios and its corresponding 95% confidence intervals were extracted and pooled. Sensitivity analyses, subgroup analyses, cumulative meta-analyses and secondary analyses were also performed to increase the stability and reliability of our results. Results 24 cohort studies were included in the study. High ZEB1 and ZEB2 levels predicted poor overall survival, meanwhile high ZEB2 levels predicted poor disease free survival for digestive cancer patients. From subgroup analyses we observed ZEB1 was found to be significantly associated with poor overall survival for patients with pancreatic cancer, gastric cancer and colorectal cancer, while ZEB2 was found to be significantly associated with poor overall survival for patients with hepatocellular carcinoma and gastric cancer. Furthermore, by conducting secondary analyses we confirmed both ZEB1 and ZEB2 played important roles in gastric cancer prediction. In addition, we found high ZEB1 and ZEB2 expression were significantly associated with depth of invasion, lymph node metastasis and TNM stage in digestive cancer patients. Conclusions The present study validated the prognostic value and clinicopathological association of ZEB1 and ZEB2 in digestive cancers, especially in gastric cancer.

Association between dioxin and cancer incidence and mortality: a meta-analysis

The objective of the present study was to systematically assess the association between dioxin/2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cancer incidence and mortality. Systematic literature searches were conducted until July 2015 in Pubmed, Embase and Cochrane library to identify relevant studies. A random-effects model was applied to estimate the pooled odds ratio (OR), risk ratio (RR), standard incidence ratio (SIR) or standard mortality ratio (SMR) for cancer incidence or mortality. In addition, dose-response, meta-regression, subgroup, and publication bias analyses were conducted. Thirty-one studies involving 29,605 cancer cases and 3,478,748 participants were included. Higher external exposure level of TCDD was significantly associated with all cancer mortality (pooled SMR = 1.09, 95% CI: 1.01–1.19, p = 0.04), but not all cancer incidence (pooled RR = 1.01, 95% CI: 0.97–1.06, p = 0.49). Higher blood level of TCDD was both significantly associated with all cancer incidence (pooled RR = 1.57, 95% CI: 1.21–2.04, p = 0.001) and all cancer mortality (pooled SMR = 1.45, 95% CI: 1.25–1.69, p < 0.001). Subgroup analysis suggested that higher external exposure and blood level of TCDD were both significantly associated with the mortality caused by non-Hodgkin’s lymphoma. In conclusion, external exposure and blood level of TCDD were both significantly associated with all cancer mortality, especially for non-Hodgkin’s lymphoma.

Association between urinary phthalate metabolites and risk of breast cancer and uterine leiomyoma

OBJECTIVE The objective of this study was to systematically assess the association between urinary phthalate metabolites and risk of breast cancer and uterine leiomyoma. METHODS Standard meta-analysis and bioinformatics analysis were conducted based on electronic databases. RESULTS No significant association was observed between total urinary phthalate metabolites and risk of breast cancer or uterine leiomyoma. However, MECPP was positively associated with breast cancer risk, and DEHP metabolites were associated with increased risk of breast cancer as well as uterine leiomyoma. Enrichment pathway analysis suggested p53 signaling pathway, mechanism of gene regulation by PPARα, apoptotic signaling in response to DNA damage and ATM signaling pathway might be involved to account for the association. CONCLUSION Significantly positive association was observed between DEHP metabolites and risk of breast cancer and uterine leiomyoma, especially for MECPP in breast cancer.

Corrigendum: Association between dioxin and cancer incidence and mortality: a meta-analysis

Corrigendum: Association between dioxin and cancer incidence and mortality: a meta-analysis