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Original article
Gene expression profiling-derived immunohistochemistry signature with high prognostic value in colorectal carcinoma
  1. Wenjun Chang1,
  2. Xianhua Gao2,
  3. Yifang Han1,
  4. Yan Du1,
  5. Qizhi Liu2,
  6. Lei Wang3,
  7. Xiaojie Tan1,
  8. Qi Zhang,
  9. Yan Liu1,1,
  10. Yan Zhu4,
  11. Yongwei Yu4,
  12. Xinjuan Fan3,
  13. Hongwei Zhang1,
  14. Weiping Zhou5,
  15. Jianping Wang3,
  16. Chuangang Fu2,
  17. Guangwen Cao1
  1. 1Department of Epidemiology, Second Military Medical University, Shanghai, China
  2. 2Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
  3. 3Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  4. 4Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China
  5. 5Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
  1. Correspondence to Professor Guangwen Cao, Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai 200433, China; gcao{at}smmu.edu.cn

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.

Design 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.

  • Colorectal Cancer

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