Prognostic and Clinicopathological Significance of MUC Family Members in Colorectal Cancer: A Systematic Review and Meta-Analysis.
ABSTRACT: Objective:To assess the association between MUC expression levels in colorectal cancer (CRC) tissues and prognosis and investigate the associations between MUC expression levels and CRC clinicopathological characteristics. Methods:The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception through September 13, 2019, to identify studies investigating the association between MUC expression levels in CRC tissues and prognosis. Pooled hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CIs) were used to evaluate associations between MUC expression levels and prognosis or clinicopathological characteristics, respectively. The heterogeneity between studies was assessed by the I 2 values, whereas the likelihood of publication bias was assessed by Egger's linear regression and Begg's rank correlation test. Results:Among 33 included studies (n = 6032 patients), there were no associations between combined MUC phenotype expression levels and overall survival (OS) or disease-free survival (DFS)/relapse-free survival (RFS) in patients with CRC. In subgroup analyses, the upregulated MUC1 expression (HR = 1.50; 95% CI, 1.29-1.74; P < 0.00001) was associated with poor OS. However, the upregulated MUC2 expression (HR = 0.64; 95% CI, 0.52-0.79; P < 0.00001) was associated with better OS. Furthermore, a high level of MUC1 expression (HR = 1.99; 95% CI, 0.99-3.99; P = 0.05) was associated with shorter DFS/RFS. However, patients with a low level of MUC2 tumors showed better DFS/RFS than patients with a high level of MUC2 tumors (HR = 0.71; 95% CI, 0.49-1.04; P = 0.08; P = 0.0.009, I 2 = 67%) and MUC5AC expression (HR = 0.56; 95% CI, 0.38-0.82; P = 0.003) was associated with longer DFS/RFS. In addition, a high level of MUC1 expression was associated with CRC in the rectum, deeper invasion, lymph node metastasis, distant metastasis, advanced tumor stage, and lymphatic invasion. A high level of MUC2 expression had a protective effect. High secretion of MUC5AC is associated with colon cancer compared with rectal cancer. Conclusion:The protein expression of MUC1 might be a poor biomarker in colorectal cancer and might play a role in tumor transformation and metastasis. However, the protein expression of MUC2 expression might have a protective effect. Furthermore, randomized controlled trials (RCTs) of large patients are needed to confirm the results.
Project description:Background:The reliability of MUC2 as a prognostic marker in colorectal cancer (CRC) is controversial. This study evaluated the association between MUC2 expression levels in CRC tissues and prognosis. Methods:The PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disc (CBMdisc), Wanfang Database, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies exploring the relationship between MUC2 expression in CRC tissues and overall survival (OS). Pooled hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs) were used to evaluate the associations between MUC2 expression levels and prognosis and MUC2 expression levels and CRC clinicopathological characteristics, respectively. Results:The meta-analysis included 11 studies (2619 patients). Low MUC2 expression level was significantly associated with poor OS (HR, 1.67; 95% CI, 1.43-1.94; P < 0.00001) and disease-free survival (DFS)/recurrence-free survival (RFS) (HR, 1.60; 95% CI, 1.21-2.12; P = 0.001) in patients with CRC. Low MUC2 expression level was associated with advanced TNM stage (RR, 1.42; 95% CI, 1.26-1.60; P < 0.00001), lymph node metastasis (RR, 1.41; 95% CI, 1.25-1.60; P < 0.00001), lymphatic invasion (RR,1.64; 95% CI, 1.26-2.12; P = 0.0002), rectal tumor site (RR, 1.26; 95% CI, 1.09-1.46; P = 0.001), and large tumor size (RR,1.32; 95% CI, 1.02-1.70; P = 0.03). There were no associations between low MUC2 expression level and gender, histological grade, depth of invasion, and distant metastasis. Conclusion:The low levels of MUC2 in CRC tissues are poor prognostic factor independent of stage or other well-recognized markers of later-stage disease. Large well-designed cohort studies are required to validate MUC2 as a biomarker for poor prognosis in CRC.
Project description:BACKGROUND:Accumulating evidence supports the overexpression of mucin 1 (MUC1) in colorectal cancer (CRC), but the value of elevated MUC1 expression remains controversial. Here, we evaluated the prognostic and clinicopathological value of MUC1 expression in CRC. MATERIALS AND METHODS:The Web of Science, PubMed, Embase, Cochrane Library, and Wanfang databases, as well as the China Biology Medicine disc (CBMdisc) and China National Knowledge Infrastructure (CNKI) were searched for studies on MUC1 expression and prognosis of CRC through July 20, 2018. The pooled relative risks (RRs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated to evaluate the prognostic and clinicopathological value of MUC1 expression in CRC. The Revman version 5.3 package and STATA, version 12 were employed for pooled analysis and analysis of publication bias. RESULTS:This meta-analysis included 16 published studies. The combined analysis showed that CRC patients with high MUC1 expression had a worse clinical outcome in overall survival (OS) (HR?=?1.51, 95% CI?=?1.30-1.75, P?<.00001). In addition, high MUC1 expression was associated with higher TNM stage (RR?=?1.44, 95% CI?=?1.17-1.77, P?=?.0007), greater depth of invasion (RR?=?1.30, 95% CI?=?1.10-1.53, P?=?.002), and lymph node metastasis (RR?=?1.47, 95% CI?=?1.20-1.80, P?=?.0002) of CRC. However, the elevated MUC1 expression was not related to disease-free survival/recurrence-free survival (DFS/RFS) (HR?=?1.51, 95% CI?=?0.78-2.89, P?=?.22), histological grade (RR?=?1.15, 95% CI?=?0.96-1.38, P?=?.12), gender (RR?=?0.95; 95% CI?=?0.83-1.08, P?=?.44), tumor size (RR?=?1.11, 95% CI?=?0.85-1.44, P?=?.44), tumor site (RR?=?1.01, 95% CI?=?0.88-1.16, P?=?.84), or mucinous component (RR?=?0.83, 95% CI?=?0.60-1.14, P?=?.24) in CRC. CONCLUSION:Our findings indicated that high MUC1 expression represents a marker of poor prognosis in CRC. Meanwhile, elevated MUC1 expression was associated with advanced TNM stage, greater depth of invasion, and lymph node metastasis.
Project description:PURPOSE:Several studies have evaluated surgical resection of pulmonary metastases as a standard treatment option for colorectal cancer (CRC) patients with resectable pulmonary metastases. However, the role of peri-operative chemotherapy after complete resection of pulmonary metastases from CRC patients is still controversial. This systematic review and meta-analysis is aimed to investigate the clinical efficacy of peri-operative chemotherapy after resection of CRC pulmonary metastases. METHODS:PubMed, the Cochrane Library databases, and Embase were searched for studies evaluating the effect of peri-operative chemotherapy on the survival of patients with CRC after pulmonary metastasectomy. The hazard ratio (HR) was used for analyzing overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS)/disease-free survival (DFS). RESULTS:Eight studies were included in the final analysis. The outcome showed that peri-operative chemotherapy had a significant favourable effect on OS (HR 0.83, 95% CI 0.75-0.92, p?<?0.05) and PFS/RFS/DFS (HR 0.67, 95% CI 0.53-0.86, p?<?0.05) in patients who received pulmonary metastasectomy. Multivariate analysis also validated this result (OS: HR 0.56, 95% CI 0.36-0.86, p?<?0.05; PFS/RFS/DFS: HR 0.64, 95% CI 0.46-0.87, p?<?0.05). There was a significant benefit in peri-operative group on OS and PFS/RFS/DFS in studies with R0 resection of pulmonary metastases (OS: HR 0.72, 95% CI 0.53-0.97, p?<?0.05; PFS/RFS/DFS: HR 0.72, 95% CI 0.54-0.95, p?<?0.05) and metachronous pulmonary metastases (OS: HR 0.40, 95% CI 0.22-0.75, p?<?0.05; PFS/RFS/DFS: HR 0.67, 95% CI 0.49-0.92, p?<?0.05). CONCLUSION:Our meta-analysis demonstrated a significant difference in favor of peri-operative chemotherapy in CRC patients who underwent resection of pulmonary metastases. More clinical data and studies are needed to validate the findings of our study.
Project description:To systematically evaluate the prognostic-predictive capability of Bcl-2 in colorectal cancer (CRC).A systematic literature search was conducted using PubMed, Web of Science and EMBASE databases. Any eligible study must meet the following criteria: (1) bcl-2 expression was evaluated in human CRC tissues by immunohistochemistry; (2) assessment of the relationships between bcl-2 expression and overall survival (OS), disease free survival (DFS), recurrent free survival (RFS) or clinic-pathological characteristics of CRC was included; (3) sufficient information was provided to estimate the hazard ratio (HR) or odds ratio and their 95% confidence intervals (CIs); and (4) the study was published in English. The impact of Bcl-2 expression on survival of CRC patients were evaluated through this meta-analysis.A total of 40 eligible articles involving 7658 patients were enrolled in our final analysis. We drew the conclusion that Bcl-2 high expression was significantly correlated with favorable OS (pooled HR = 0.69, 95%CI: 0.55-0.87, P = 0.002) and better DFS/RFS (pooled HR = 0.65, 95%CI: 0.50-0.85, P = 0.001). Additionally, the subgroup analysis suggested that Bcl-2 overexpression was significantly associated with prognosis (OS) especially in patients came from Europe and America but not Asian and patients who did not receive any adjuvant therapy before surgery. Finally, our present results indicated that expression of bcl-2 protein was associated with high differentiation grade and A/B Ducks' stage.Bcl-2 high expression was significantly correlated with favorable OS and better DFS/RFS. Hence, we propose that Bcl-2 may be a valuable prognostic-predictive marker in CRC.
Project description:Mucin glycoprotein's are major components of mucus and are considered an important class of tumor associated antigens. The objective of this study was to investigate the expression of human MUC genes (MUC1, MUC2, MUC5B, MUC5AC and MUC8) in human endometrium and cervix, and to compare and quantitate the expression of MUC genes in normal and cancerous tissues.Slot blot techniques were used to study the MUC gene expression and quantitation.Of the five-mucin genes studied, MUC1, MUC5B and MUC8 showed high expression levels in the normal and cancerous endometrial and cervical tissues, MUC2 and MUC5AC showed considerably lower expression. Statistically, higher levels of MUC1, MUC5B and MUC8 were observed in endometrial adenocarcinomas compared to normal tissues. In contrast, only MUC1 levels increased with no significant changes in expression of MUC5B and MUC8 in cervical tumors over normal cervical tissues.Endometrial tumors showed increased expression of MUC1, MUC5B and MUC8 over normal tissues. Only MUC1 appears to be increase, in cervical tumors. All the studied tissues showed high and consistent expression of MUC8 mRNA. Low to neglible levels of MUC2 and MUC5AC were observed in all studied endometrial and cervical tissues.
Project description:Colorectal cancer (CRC) is one of the most common cancers worldwide. However, the prognostic and clinical value of platelet-lymphocyte ratio (PLR) in colorectal cancer was still unclear, which attracted more and more researchers' considerable attention. We performed a systematic review and meta-analysis to investigate the relationship between PLR and survival as well as clinical features of CRC update to September 2016. The hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) were calculated to access the association. We included 24 eligible studies with a total of 13719 patients. Elevated PLR predicted shorter overall survival (OS) (HR=1.47; 95%CI, 1.28-1.68; p<0.001), poorer disease-free survival (DFS) (HR=1.51; 95% CI, 1.2-1.91; p=0.001), and worse recurrence-free survival (RFS) (HR=1.39; 95% CI, 1.03-1.86; p=0.03), but had nothing to do with Cancer-specific survival (CSS) (HR=1.14; 95% CI, 0.92-1.42; p=0.223). After trim and fill method, the connection between PLR and DFS disappeared (HR=1.143; 95%CI, 0.903-1.447; p=0.267). By subgroup analyze, we found that increased PLR predicated a worse OS and DFS in patients who underwent surgery, and this prognostic role also shown both in metastatic and nonmetastatic patients. In addition, elevated PLR was associated with poorly differentiated tumor (OR=1.51; 95% CI, 1.26-1.81; p<0.001), higher tumor stage (OR=1.25; 95% CI, 1.05-1.49; p=0.012), lymphovascular invasion (LVI) (OR=1.25; 95% CI, 1.09-1.43; p=0.001), and the recurrence of CRC (OR=2.78; 95% CI, 1.36-5.68; p=0.005). We indicated that pretreatment PLR was a good prognostic marker for CRC patients. High PLR was related to worse OS, RFS and poor clinical characteristics.
Project description:BACKGROUND AND OBJECTIVE:Studies examining the prognostic value of the BRAF mutation on relapse-free survival (RFS), disease-free survival (DFS) and overall survival (OS) in stage II/III colorectal cancer (CRC) patients receiving curative resection and adjuvant chemotherapy so far showed discrepant results. Therefore, a meta-analysis of relevant studies was performed for clarification. METHODS:Randomized trials of stage II/III colorectal cancer treated with curative resection followed by adjuvant chemotherapy were selected to conduct a meta-analysis. The necessary descriptive and statistical information such as hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from published survival data. RESULTS:Seven phase III randomized clinical trials (RCTs) including 1,035 BRAF mutation stage II/III CRC patients receiving curative resection and adjuvant chemotherapy were analyzed. Overall, BRAF mutation resulted in poorer OS (HR = 1.42, 95% CI: 1.25-1.60; P < 0.00001), and poorer DFS (HR = 1.26, 95% CI: 1.07-1.48, P = 0.006) compared with BRAF wild-type CRC. The prognostic role on RFS could not be elucidated in the meta-analysis because of limited data. CONCLUSIONS:BRAF mutation was significantly related with shorter DFS and OS among stage II/III CRC patients receiving adjuvant chemotherapy after curative resection. Its prognostic role for RFS needs to be further analyzed when more data is available.
Project description:<h4>Introduction</h4>Colorectal cancer (CRC) is one of the world's three most common cancers and its incidence is rising. To identify patients who benefit from adjuvant therapy requires novel biomarkers. The regenerating islet-derived gene (REG) 4 belongs to a group of small secretory proteins involved in cell proliferation and regeneration. Its up-regulated expression occurs in inflammatory bowel diseases also in gastrointestinal cancers. Reports on the association of REG4 expression with CRC prognosis have been mixed. Our aim was to investigate tumor REG4 expression in CRC patients and its coexpression with other intestinal markers.<h4>Methods</h4>Tumor expression of REG4 was evaluated by immunohistochemistry in 840 consecutive surgically treated CRC patients at Helsinki University Central Hospital. Expression of MUC1, MUC2, MUC5AC, synapthophysin, and chromogranin was evaluated in a subgroup of 220 consecutively operated CRC patients. REG4 expression with clinicopathological parameters, other intestinal markers, and the impact of REG4 expression on survival were assessed.<h4>Results</h4>REG4 expression associated with favorable clinicopathological parameters and with higher overall survival from non-mucinous CRC (p?=?0.019). For such patients under 65, its expression was an independent marker of lower risk of death within 5 years that cancer; univariable hazard ratio (HR)?=?0.57; 95% confidence interval (CI) (0.34-0.94); multivariable HR?=?0.55; 95% CI (0.33-0.92). In non-mucinous CRC, REG4 associated with positive MUC2, MUC4, and MUC5AC expression.<h4>Conclusion</h4>We show, to our knowledge for the first time, that REG4 IHC expression to be an independent marker of favorable prognosis in non-mucinous CRC. Our results contradict those from studies based on quantification of REG4 mRNA levels, a discrepancy warranting further studies.
Project description:Platelet to lymphocyte ratio (PLR) is a parameter reflecting inflammatory responses in patients with cancer. Several studies have investigated the prognostic value of PLR in patients with colorectal cancer (CRC); however, the results are controversial. Thus, we carried out a meta-analysis to evaluate the association between PLR and CRC prognostication. Relevant articles were retrieved through PubMed, Embase, and Web of Science, and pooled hazard ratio (HR) and 95% confidence interval (CI) were computed by using STATA V.12.0. Both the random-effects model and fixed-effects model were utilized. A total of 13 studies (14 cohorts) with 8,601 patients were included in the meta-analysis. Pooled HRs and 95% CIs demonstrated that increased PLR predicted poor overall survival (OS) (HR = 1.81, 95%CI:1.42-2.31, p<0.001; I2 = 65%, Ph = 0.002), disease-free survival (DFS) (HR = 1.84, 95%CI:1.22-2.76, p = 0.003; I2 = 78.3%, Ph<0.001) and recurrence-free survival (RFS) (HR = 1.84, 95%CI:1.41-2.41, p<0.001; I2 = 0, Ph = 0.686), although this was not the case for cancer-specific survival (CSS) (HR = 1.75, 95%CI:0.59-5.17, p = 0.309; I2 = 66.2%, Ph = 0.085) or time to recurrence (TTR) (HR = 1.21 95%CI:0.62-2.36, p = 0.573;I2 = 58.4%, Ph = 0.121). Subgroup analysis showed that PLR enhanced the prognostic value for OS in Caucasian patients, in small sample studies and for metastatic disease; however, this was not the case with rectal cancer. Furthermore, elevated PLR predicted reduced DFS in Caucasians and not in Asians. In conclusion, our meta-analysis showed that high PLR was a significant biomarker for poor OS, DFS, and RFS in patients with CRC; however, it had no association with CSS or TTR.
Project description:BACKGROUND:Studies have indicated that statins influence the risks and mortality rates of several types of solid tumors. However, the association between statin use and survival in patients with colorectal cancer (CRC) remains unclear. METHODS:We searched the PubMed and Embase databases for relevant studies published up to September 2014 that assessed statin use and CRC prognosis. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). The secondary outcomes were disease-free survival (DFS) and recurrence-free survival (RFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled with Mantel-Haenszel random-effect modeling. All statistical tests were two-sided. RESULTS:Four studies on post-diagnosis statin therapy and five studies on pre-diagnosis statin use were included in our meta-analysis of 70,608 patients. Compared with the non-users, the patients with post-diagnosis statin use gained survival benefits for OS (HR 0.76; 95% CI: 0.68 to 0.85, P<0.001) and CSS (HR 0.70; 95% CI: 0.60 to 0.81, P<0.001). In addition, we observed that pre-diagnosis statin use prolonged the survival of patients with CRC for OS (HR 0.70; 95% CI: 0.54 to 0.91, P=0.007) and CSS (HR 0.80; 95% CI: 0.74 to 0.86, P<0.001). However, we did not observe a survival benefit for DFS (HR 1.13; 95% CI: 0.78 to 1.62, P=0.514) or RFS (HR 0.98; 95% CI: 0.36 to 2.70, P=0.975) in the CRC patients with post-diagnosis statin use. CONCLUSIONS:Statin use before or after cancer diagnosis is related to reductions in overall and cancer-specific mortality in colorectal cancer survivors.