title: An in situ molecular signature to predict early recurrence in hepatitis B virus-related hepatocellular carcinoma.
abstract: OBJECTIVE
  To develop an in situ molecular signature to predict postsurgical recurrence in hepatocellular carcinoma (HCC) patients.
  
  
  METHODS
  Immunohistochemistry was performed using tissue microarrays containing both tumoral and peri-tumoral regions of the advancing tumor edge from 336 HCC patients (289 were positive for hepatitis B virus) who underwent curative resection. Forty-nine variables were analyzed in the training set (n=151) using support vector machine and stepwise algorithms to develop a classifier to predict recurrence within 1 year, which was mainly caused by invasion or metastasis from the primary tumors. The classifier was further validated in an independent cohort of 185 patients (71 internal and 114 external).
  
  
  RESULTS
  The final signature was composed of eight IHC features: CD80(T), B7-DC(T), HLA-DR(P), FasL(P), Bcl-2(T), Ki-67(T), cyclin D1(T), and CK19(T). In the independent test set, this classifier reliably predicted recurrence within 1 year (sensitivity, 69.1%; specificity, 65.0%) with an odds ratio of 4.149 (95% CI, 2.189-7.864). Based on a multivariate logistic model, the in situ molecular signature provided significant predictive power independent of tumor number, tumor size, vascular invasion and BCLC classification (p=0.001). The highest potential clinical impact of the classifier was observed in early-stage (BCLC classification 0-A) patients (p<0.0001), and the classifier was also predictive of the time-to-recurrence and overall survival (both p<0.0001).
  
  
  CONCLUSIONS
  This in situ molecular classifier could provide a novel approach to identify patients who are at greatest risk for postsurgical recurrence of HCC and may benefit from intensive clinical follow-up or chemopreventive strategies.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen (Zhongshan) University, Guangzhou, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Tong
authors.initials: T
authors.lastname: Ding
authors.forename: Qi
authors.initials: Q
authors.lastname: He
authors.forename: Xing-Juan
authors.initials: XJ
authors.lastname: Yu
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Wu
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Yun
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Chun-Kui
authors.initials: CK
authors.lastname: Shao
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Pan
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Yin
authors.forename: Jun
authors.initials: J
authors.lastname: Min
authors.forename: Shi-Mei
authors.initials: SM
authors.lastname: Zhuang
authors.forename: Limin
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000473:pathology / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology / Q000601:surgery; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D046888:Tissue Array Analysis