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Prognostic and clinicopathological value of MUC1 expression in colorectal cancer: A meta-analysis.

ABSTRACT: 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.

SUBMITTER: Li C

PROVIDER: S-EPMC6831235 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Prognostic and clinicopathological value of MUC1 expression in colorectal cancer: A meta-analysis.

Li Chao C Liu Tao T Yin Libin L Zuo Didi D Lin Yuyang Y Wang Lei L

Medicine 20190301 9

<h4>Background</h4>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.<h4>Materials and methods</h4>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 s ...[more]

PMID: 30817589

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Project description:BackgroundThe prognostic value of HIFs in colorectal cancer was evaluated in a large number of studies, but the conclusions were inconclusive. Meanwhile, clinicopathologic differences of HIF-1? and HIF-2? were rarely compared in recent studies.MethodologyIdentical search strategies were used to search relevant literatures in the PubMed and Web of Science databases. The prognostic significances and clinicopathological differences of HIFs in CRC were analyzed.Principal findingsA total of 23 studies comprising 2984 CRC patients met the inclusion criteria. The results indicated that overexpressed HIFs were significantly associated with increase of mortality risk, including overall survival (OS) (HR 2.06 95%CI 1.55-2.74) and disease free survival (HR 2.84, 95%CI 1.87-4.31). Subgroup analysis revealed that both overexpressed HIF-1? and HIF-2? had correlations with worse prognosis. The pooled HRs were 2.01 (95% CI: 1.55-2.6) and 2.07(95% CI: 1.01-4.26). Further subgroup analysis on HIF-1? was performed by study location, number of patients, quality score and cut-off value. The results showed that HIF-1? overexpression was significantly associated with poor OS, particularly in Asian countries (HR 2.3, 95% CI: 1.74-3.01), while not in European or other countries. In addition, overexpression of HIF-1? was closely related with these clinicopathological features, including Dukes' stages (OR 0.39, 95% CI: 0.17-0.89), UICC stages (OR 0.42 95% CI: 0.3-0.59), depth of invasion (OR 0.71, 95% CI: 0.51-0.99), lymphnode status (OR 0.49, 95% CI: 0.32-0.73) and metastasis (OR 0.29, 95% CI: 0.11-0.81). While overexpression of HIF-2? was only associated with grade of differentiation (OR 0.48, 95% CI: 0.29-0.81).ConclusionsThis study showed that both HIF-1? and HIF-2? overexpression were associated with an unfavorable prognosis. HIF-1? overexpression seemed to be associated with worse prognosis in Asian countries. Additionally, HIF-1? and HIF-2? indicated distinct clinicopathologic features.

Project description:Purpose: The PPFIA gene family (PPFIA1, PPFIA2, PPFIA3, and PPFIA4) is associated with multiple human diseases, particularly malignant tumors. However, the expression and prognostic value of the PPFIA family in human colorectal cancers (CRCs) have not been reported. Materials and methods: In this study, several databases, including Oncomine, UALCAN, and the cancer cell line encyclopedia, were used to compare differences in PPFIA1, PPFIA2, PPFIA3, and PPFIA4 expression between normal colon samples and CRCs. The expression levels of these four proteins were used to evaluate the survival of patients with CRC, as determined by the Cancer Genome Atlas Program (TCGA) portal and gene expression profiling interactive analysis (GEPIA) databases. Western blotting and reverse transcription-polymerase chain reaction were performed to detect protein and mRNA levels of PPFIA1, PPFIA3, and PPFIA4, respectively. Immunohistochemical (IHC) staining was used to detect the correlation between PPFIA4 expression and the degree of CRC malignancy. Furthermore, potential miRNAs targeting PPFIA4 in CRCs were studied and confirmed. Results: Bioinformatic analysis showed that the mRNA levels of PPFIA1, PPFIA3, and PPFIA4 were higher in CRC tissue samples than in normal colon tissue. Both mRNA and protein expression of PPFIA1, PPFIA3, and PPFIA4 were increased in the CRC cell lines LoVo and Hct116 compared with the normal colon epithelial cell line. Only PPFIA4 was associated with the prognosis of patients with CRC, which was confirmed by TCGA portal and GEPIA. IHC staining confirmed that the expression of PPFIA4 was higher in CRC tissues than in normal colon tissues and also increased in poorly differentiated CRC tissues and lymph node metastatic foci in comparison with well-differentiated CRC tissues and moderately differentiated CRC tissues. Functional annotation enrichment analysis indicated that the top 100 genes co-expressed with PPFIA4 were enriched in the G-protein coupled peptide receptor activity, leukotrience B4 receptor activity, and peroxisome proliferator-activated receptors and hypoxia-inducible factor-1 signaling pathways. In addition, miR-485-5p negatively regulates the expression of PPFIA4. Conclusion:PPFIA4 expression is associated with the development of CRCs and may be a novel potential prognostic marker for human CRCs.

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Dataset Information

Prognostic and clinicopathological value of MUC1 expression in colorectal cancer: A meta-analysis.

Publications

Prognostic and clinicopathological value of MUC1 expression in colorectal cancer: A meta-analysis.

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