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Overexpression of CXCR2 predicts poor prognosis in patients with colorectal cancer.

ABSTRACT: Colorectal cancer is a heterogeneous disease. Although many risk factors are used to predict colorectal cancer patients' prognosis after surgical resection, new prognostic factors are still needed to be defined to promote predictive efficacy of prognosis and further guide therapies. Herein, we identified the prognostic significance of CXCR2 in colorectal cancer patients. We retrospectively analysed 134 patients with colorectal cancer who underwent minimally invasive surgery between 2010 and 2011. The overall cohort was divided into a training set (n = 78) and a validation set (n = 56). We detected CXCR2 expression using immunohistochemical staining and defined the cut-off value using X-tile program. Next, we analysed the association between CXCR2 expression and clinicopathologic features in training and validation sets. High expression of CXCR2 was associated with Dukes stage (P = 0.018), tumor invasion (P = 0.018) and liver metastasis (P = 0.047). Multivariate COX regression analyses confirmed that high CXCR2 level was an independent prognostic risk factor for both overall survival and disease free survival. Kaplan-Meier survival analysis demonstrated that patients with high expression of CXCR2 had a poor overall survival and disease free survival even in low-risk group (I + II). This indicated that CXCR2 can help to refine individual risk stratification. In addition, we established Nomograms of all significant factors to predict 3- or 5-years overall survival and disease free survival. Moreover, we found the combination of CXCR2 and its ligand CXCL5 had more significant value in predicting the prognosis than single CXCR2 factor.

SUBMITTER: Zhao J

PROVIDER: S-EPMC5438662 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Overexpression of CXCR2 predicts poor prognosis in patients with colorectal cancer.

Zhao Jingkun J Ou Baochi B Feng Hao H Wang Puxiongzhi P Yin Shuai S Zhu Congcong C Wang Shenjie S Chen Chun C Zheng Minhua M Zong Yaping Y Sun Jing J Lu Aiguo A

Oncotarget 20170401 17

Colorectal cancer is a heterogeneous disease. Although many risk factors are used to predict colorectal cancer patients' prognosis after surgical resection, new prognostic factors are still needed to be defined to promote predictive efficacy of prognosis and further guide therapies. Herein, we identified the prognostic significance of CXCR2 in colorectal cancer patients. We retrospectively analysed 134 patients with colorectal cancer who underwent minimally invasive surgery between 2010 and 2011 ...[more]

PMID: 28415702

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Project description:Background: Semaphorin 6b (SEMA6B) is a member of the semaphorin axon-guidance family and has been demonstrated to both induce and inhibit tumor progression. However, the role of SEMA6B in colorectal cancer (CRC) has remained unclear. This study sought to explore the promising prognostic biomarker for CRC and to understand the expression pattern, clinical significance, immune effects, and biological functions of SEMA6B. Methods: SEMA6B expression in CRC was evaluated via multiple gene and protein expression databases and we identified its prognostic value through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Correlations between SEMA6B expression and components of the tumor immune microenvironment were analyzed by packages implemented in R, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and Tumor-Immune System Interactions database (TISIDB). RNA interference was performed to silence the expression of SEMA6B to explore its biological roles in the colon cancer cell lines HCT116 and LoVo. Results: The messenger RNA (mRNA) level of SEMA6B and the protein expression were higher in CRC tissues than adjacent normal tissues from multiple CRC datasets. High SEMA6B expression was significantly associated with dismal survival. Multivariate Cox regression analysis demonstrated that SEMA6B was an independent prognostic factor for progression-free survival (PFS). The nomogram showed a favorable predictive ability in PFS. Functional enrichment analysis and the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm revealed that the gene cluster associated with the high SEMA6B group were prominently involved in immune responses and inflammatory activities. Notably, SEMA6B expression was positively correlated with infiltrating levels of CD4+ T cells, macrophages, myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), neutrophils, and dendritic cells. Moreover, SEMA6B expression displayed strong correlations with diverse marker sets of immunosuppressive cells in CRC. Integrative analysis revealed that immunosuppressive molecules and immune checkpoints were markedly upregulated in CRC samples with high SEMA6B expression. Furthermore, knockdown of SMEA6B in colon cancer cells significantly inhibited cell proliferation, migration, invasion and reduced the mRNA levels of immunosuppressive molecules. Conclusion: Our findings provide evidence that high SEMA6B expression correlated with adverse prognosis and the tumor immunosuppressive microenvironment in CRC patients. Therefore, SEMA6B may serve as a novel prognostic biomarker for CRC, which offers further insights into developing CRC-targeted immunotherapies.

Dataset Information

Overexpression of CXCR2 predicts poor prognosis in patients with colorectal cancer.

Publications

Overexpression of CXCR2 predicts poor prognosis in patients with colorectal cancer.

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