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ITGB4 is a novel prognostic factor in colon cancer.

ABSTRACT: Integrin ?4 (ITGB4) has been reported to be involved in carcinomas. Currently, ITGB4 has been characterized in colon cancer, however, its clinical significance is not very clear. In the present study, we utilized the large public datasets from NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and collected clinical samples in our center to investigate the transcriptional expressions of ITGB4 in colon cancer, and then explored the associations of ITGB4 with clinicopathological features and overall survival. The statistical analyses suggested that ITGB4 mRNA expressions were up-regulated significantly in colon cancer. High ITGB4 expression was observed to be associated with elder onset age, proximal tumor location, and high microsatellite instability (MSH) status. Further, Kaplan-Meier curves and univariate analysis demonstrated high ITGB4 expression was significantly associated with unfavorable overall survival in colon cancer (HR=1.292, 95%CI=1.084-1.540, P=0.004). And significant association was also found after adjusting the confounding factors including age, gender, and stage (adjusted HR=1.254, 95%CI=1.050-1.497, P=0.012). The annotation of ITGB4 co-expressed genes suggested the pathways including cell growth, positive regulation of cell migration, and apoptotic signaling might be involved in the potential mechanisms of ITGB4 in colon cancer development. The molecular regulation mechanism of ITGB4 ectopic expression in colon cancer was also explored and the results indicated that ITGB4 might be up-regulated by the transcription factor FOSL1 (FOS like 1, AP-1 Transcription Factor Subunit) and its promoter hypomethylation. Our results revealed that ITGB4 might be a therapeutic target and prognosis marker for individual therapy of colon cancer.

SUBMITTER: Li M

PROVIDER: S-EPMC6775604 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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ITGB4 is a novel prognostic factor in colon cancer.

Li Meng M Jiang Xia X Wang Guiqi G Zhai Congjie C Liu Ying Y Li Hongyan H Zhang Yan Y Yu Weifang W Zhao Zengren Z

Journal of Cancer 20190828 21

Integrin β4 (ITGB4) has been reported to be involved in carcinomas. Currently, ITGB4 has been characterized in colon cancer, however, its clinical significance is not very clear. In the present study, we utilized the large public datasets from NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and collected clinical samples in our center to investigate the transcriptional expressions of ITGB4 in colon cancer, and then explored the associations of ITGB4 with clinicopa ...[more]

PMID: 31602273

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Project description:BACKGROUND:A large number of patients suffer recurrence after curative resection, and mortality from colon cancer remains high. The role of systemic inflammatory response, as reflected by neutrophil-to-lymphocyte ratio (NLR), in cancer recurrence and death has been increasingly recognized. This study aimed to analyze long-term oncologic outcomes of Stage II-III colon cancer to examine the prognostic value of NLR using a propensity score analysis. METHODS:A total of 375 patients with colon cancer underwent radical surgery between 2000 and 2014 at Tokyo Medical University Hospital. Long-term oncologic outcomes of these patients were evaluated according to NLR values. A cut-off NLR of 3.0 was used based on receiver operating characteristic curve analysis. Primary outcomes were overall survival (OS) and relapse-free survival (RFS). An analysis of outcomes according to tumor sidedness was also performed. RESULTS:Patients with lower NLR values ("lower NLR group") were more likely to have lymph node metastasis compared to those with higher NLR values ("higher NLR group") before case matching. After case matching, clinical outcomes were similar between the two groups. There were no significant differences in 5-year OS and 5-year RFS rates between the two groups before case matching based on propensity scores. After case matching, 5-year OS rates were 94.5% in the lower NLR group (n?=?135) and 87.0% in the higher NLR group (n?=?135), showing a significant difference (p?=?0.042). Five-year RFS rates were 87.8% in the lower NLR group and 77.9% in the higher NLR group, also showing a significant difference (p?=?0.032). Among patients with left-sided colon cancer in the matched cohort, 5-year OS and 5-year RFS rates were 95.2 and 87.3% in the lower NLR group (n?=?88), respectively, and 86.4 and 79.2% in the higher NLR group (n?=?71), respectively, showing significant differences (p?=?0.014 and p?=?0.047, respectively). CONCLUSIONS:The NLR is an important prognostic factor for advanced colon cancer, especially for left-sided colon cancer.

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ITGB4 is a novel prognostic factor in colon cancer.

Publications

ITGB4 is a novel prognostic factor in colon cancer.

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