Randomized Clinical Trial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2015; 21(7): 2191-2198
Published online Feb 21, 2015. doi: 10.3748/wjg.v21.i7.2191
Semaphorin 4D and hypoxia-inducible factor-1α overexpression is related to prognosis in colorectal carcinoma
Jin-Shen Wang, Chang-Qing Jing, Ke-Shu Shan, Yue-Zhi Chen, Xiao-Bo Guo, Zhi-Xin Cao, Lin-Jun Mu, Li-Pan Peng, Ming-Liang Zhou, Le-Ping Li
Jin-Shen Wang, Chang-Qing Jing, Ke-Shu Shan, Yue-Zhi Chen, Xiao-Bo Guo, Lin-Jun Mu, Li-Pan Peng, Ming-Liang Zhou, Le-Ping Li, Department of Gastrointestinal Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
Zhi-Xin Cao, Department of Pathology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
Author contributions: Wang JS, Jing CQ, Shan KS contributed equally to this work; Wang JS, Jing CQ, Shan KS, Li LP, Chen YZ, Guo XB and Mu LJ designed the research study; Wang JS, Jing CQ, Shan KS, Peng LP and Zhou ML performed the research; Guo XB, Mu LJ and Cao ZX analyzed the data; Wang JS, Jing CQ, Shan KS and Mu LJ wrote the manuscript.
Supported by Scientific Research Foundation of Shandong Province for Outstanding Young Scientist Award, No. 2009GG20002037.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Le-Ping Li, MD, Department of Gastrointestinal Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan 250021, Shandong Province, China. doctor@mail.sdu.edu.cn
Telephone: +86-531-68777198 Fax: +86-531-68776388
Received: July 13, 2014
Peer-review started: July 13, 2014
First decision: August 15, 2014
Revised: October 27, 2014
Accepted: November 7, 2014
Article in press: November 11, 2014
Published online: February 21, 2015
Abstract

AIM: To investigate semaphorin 4D (Sema4D) and hypoxia-inducible factor-1α (HIF-1α) expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance.

METHODS: Eighty-six curatively resected colorectal carcinoma patients at different stages of disease were randomly selected from the group of patients who underwent surgery, and none of them received preoperative radiochemotherapy. Normal proximal adjacent bowel tissue, which served as an internal control, was obtained from 52 randomly selected patients. Immunohistochemistry was performed to analyze the expression of Sema4D and the tumor angiogenesis-related protein HIF-1α in normal colorectal tissues and colorectal carcinoma tissues. The relationships between the expression and clinical characters and prognosis were analyzed.

RESULTS: HIF-1α and Sema4D were positively expressed in 58% and 60% of colorectal carcinoma tissues, respectively. Significantly lower expression levels were observed in normal mucosa (8% and 12%, respectively). HIF-1α and Sema4D expression was closely correlated with histological tumor type, tumor-node-metastasis (TNM) stage, and lymphatic metastasis (P < 0.05), but not with age or tumor size (P > 0.05). HIF-1α and Sema4D protein expression was significantly correlated with prognosis of colorectal carcinoma, as determined by Spearman rank correlation analysis (r = 0.567; P < 0.01). Multivariate Cox analysis revealed that only Sema4D expression played a significant role in predicting patient prognosis (P < 0.05).

CONCLUSION: These findings suggest that HIF-1α and Sema4D expression correlates with histological tumor type, TNM stage, and lymphatic metastasis in colorectal carcinoma and that Sema4D is a prognostic indicator of colorectal carcinoma.

Keywords: Colorectal carcinoma, Immunohistochemical staining, Hypoxia-inducible factor-1α, Semaphorin 4D, Prognosis

Core tip: Although originally identified in the context of neurodevelopment, semaphorin 4D (Sema4D) is also important in angiogenesis. Sema4D is widely expressed in several types of malignant solid tumors. However, its function and expression in colorectal carcinoma are not understood. This study indicates that Sema4D expression is positively correlated with HIF-1α in colorectal carcinoma and that Sema4D is a novel indicator of poor prognosis for colorectal carcinoma patients. We expect that Sema4D could be used as a reliable tool to the early and accurate prediction of tumor recurrence, and it represents a potential therapeutic target for colorectal cancer patients.