title: Gene expression profiling-derived immunohistochemistry signature with high prognostic value in colorectal carcinoma.
abstract: OBJECTIVE
  Gene expression profiling provides an opportunity to develop robust prognostic markers of colorectal carcinoma (CRC). However, the markers have not been applied for clinical decision making. We aimed to develop an immunohistochemistry signature using microarray data for predicting CRC prognosis.
  
  
  METHODS
  We evaluated 25 CRC gene signatures in independent microarray datasets with prognosis information and constructed a subnetwork using signatures with high concordance and repeatable prognostic values. Tumours were examined immunohistochemically for the expression of network-centric and the top overlapping molecules. Prognostic values were assessed in 682 patients from Shanghai, China (training cohort) and validated in 343 patients from Guangzhou, China (validation cohort). Median follow-up duration was 58 months. All p values are two-sided.
  
  
  RESULTS
  Five signatures were selected to construct a subnetwork. The expression of GRB2, PTPN11, ITGB1 and POSTN in cancer cells, each significantly associated with disease-free survival, were selected to construct an immunohistochemistry signature. Patients were dichotomised into high-risk and low-risk subgroups with an optimal risk score (1.55). Compared with low-risk patients, high-risk patients had shorter disease-specific survival (DSS) in the training (HR=6.62; 95% CI 3.70 to 11.85) and validation cohorts (HR=3.53; 95% CI 2.13 to 5.84) in multivariate Cox analyses. The signature better predicted DSS than did tumour-node-metastasis staging in both cohorts. In those who received postoperative chemotherapy, high-risk score predicted shorter DSS in the training (HR=6.35; 95% CI 3.55 to 11.36) and validation cohorts (HR=5.56; 95% CI 2.25 to 13.71).
  
  
  CONCLUSIONS
  Our immunohistochemistry signature may be clinically practical for personalised prediction of CRC prognosis.
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xinjuan
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chuangang
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D017024:Chemotherapy, Adjuvant; D002681:China; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil
keywords: Colorectal Cancer