Oncotarget

Research Papers:

Periostin expression in intra-tumoral stromal cells is prognostic and predictive for colorectal carcinoma via creating a cancer-supportive niche

Xiaowen Xu, Wenjun Chang, Jie Yuan, Xue Han, Xiaojie Tan, Yibo Ding, Yanxin Luo, Hui Cai, Yan Liu, Xianhua Gao, Qizhi Liu, Yongwei Yu, Yan Du, Hao Wang, Liye Ma, Jianping Wang, Kun Chen, Yanqing Ding, Chuangang Fu and Guangwen Cao _

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Oncotarget. 2016; 7:798-813. https://doi.org/10.18632/oncotarget.5985

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Abstract

Xiaowen Xu1,*, Wenjun Chang2,*, Jie Yuan1,*, Xue Han3,*, Xiaojie Tan2, Yibo Ding2, Yanxin Luo4, Hui Cai2, Yan Liu2, Xianhua Gao1, Qizhi Liu1, Yongwei Yu5, Yan Du2, Hao Wang1, Liye Ma6, Jianping Wang4, Kun Chen7, Yanqing Ding8, Chuangang Fu1, Guangwen Cao2

1Department of Colorectal Surgery, The 1st Affilaited Hospital, Second Military Medical University, Shanghai, China

2Department of Epidemiology, Second Military Medical University, Shanghai, China

3Department of Chronic Diseases, Center for Diseases Control and Prevention of Yangpu District, Shanghai, China

4Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

5Department of Pathology, The 1st Affilaited Hospital, Second Military Medical University, Shanghai, China

6Department of General Surgery, The 1st Affilaited Hospital, Second Military Medical University, Shanghai, China

7Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hangzhou, China

8Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China

*These authors have contributed equally to this work

Correspondence to:

Guangwen Cao, e-mail: [email protected]

Chuangang Fu, e-mail: [email protected]

Keywords: colorectal carcinoma, periostin, fibroblast, drug-resistance, prognosis

Received: June 19, 2015     Accepted: October 30, 2015     Published: November 09, 2015

ABSTRACT

Periostin (POSTN) expression in cancer cells and circulation has been related to poor prognosis of colorectal carcinoma (CRC). However, the role of POSTN expressed in intra-tumoral stroma on CRC progression remains largely unknown. This study enrolled 1098 CRC patients who received surgical treatment in Shanghai and Guangzhou, Mainland China. In Shanghai cohort, immunohistochemistry score of stromal POSTN expression increased consecutively from adjacent mucosa, primary CRC tissues, to metastatic CRC tissues (P < 0.001), while medium- and high-stromal POSTN expression, rather than epithelial POSTN expression, independently predicted unfavorable prognoses of CRC, adjusted for covariates including TNM stage and postoperative chemotherapy in multivariate Cox models. The results in Shanghai cohort were faithfully replicated in Guangzhou cohort. Stromal POSTN expression dose-dependently predicted an unfavorable prognosis of stage III CRC patients with postoperative chemotherapy in both cohorts. POSTN derived from colonic fibroblasts or recombinant POSTN significantly promoted proliferation, anchorage independent growth, invasion, and chemo-resistance of CRC cells; whereas these effects were counteracted via targeting to PI3K/Akt or Wnt/β-catenin signaling pathway. CRC cell RKO-derived factor(s) significantly induced POSTN production in colonic fibroblasts and autocrine POSTN promoted proliferation, migration, and anchorage independent growth of fibroblasts. Conclusively, stromal POSTN is prognostic and predictive for CRC via creating a niche to facilitate cancer progression. Targeting POSTN-induced signaling pathways may be therapeutic options for metastatic or chemoresistant CRC.


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