title: Semaphorin 4D and hypoxia-inducible factor-1α overexpression is related to prognosis in colorectal carcinoma.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Jin-Shen
authors.initials: JS
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Jing
authors.affiliation: 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.
authors.forename: Ke-Shu
authors.initials: KS
authors.lastname: Shan
authors.affiliation: 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.
authors.forename: Yue-Zhi
authors.initials: YZ
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Lin-Jun
authors.initials: LJ
authors.lastname: Mu
authors.affiliation: 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.
authors.forename: Li-Pan
authors.initials: LP
authors.lastname: Peng
authors.affiliation: 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.
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Le-Ping
authors.initials: LP
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D016009:Chi-Square Distribution; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D039961:Semaphorins / Q000032:analysis*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C093224:CD100 antigen; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D039961:Semaphorins
keywords: Colorectal carcinoma; Hypoxia-inducible factor-1α; Immunohistochemical staining; Prognosis; Semaphorin 4D