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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00664

Identification and validation of tumor stromal immunotype in patients with hepatocellular carcinoma

 Wei Li1*, Jun Han1, Kefei Yuan1 and Hong Wu1*
  • 1West China Hospital, Sichuan University, China

Background: The immune landscape of hepatocellular carcinoma (HCC) is heterogeneous. This study aims to develop the immune type which could improve predictive value of HCC survival.
Methods: A total of 208 HCC patients in the testing cohort, 112 patients in the validation cohort and 365 HCC patients in the TCGA database were included in this study. Immune features were assessed by immunohistochemical staining or CIBERSORT method. We constructed prognostic classifiers by LASSO COX analyses in the TCGA cohort, which identified five features out of the 22 types of immune cells.
Results: The formulas based on the immunohistochemical staining are as follows: ISOS= 0.648* Macrophagestromal + 0.444*Neutrophilsstromal + 0.218*Tregsstromal – 0.703*Memory T cellsstromal; ISDFS = 0.285*B cellsstromal + 0.494*Neutrophilsstromal + 0.431*Tregsstromal – 0.736*Memory T cellsstromal. We classified HCC patients into immune type A subgroup (IS-A) and type B subgroup (IS-B) based on immune scores. The immune type was an independent prognostic indicator for disease-free survival (DFS) and overall survival (OS) in both testing and validation cohorts. Two nomograms (for OS and DFS) that integrated the immune type and clinicopathologic risk factors also showed good predictive accuracy and discriminatory power. IS-A group was correlated with higher immune checkpoint molecule expression. In addition, patients with IS-A and IS-B had distinct mutation signature.
Conclusion: The immune types could predict survival and recurrence of HCC effectively. In addition, the immunosuppressive pathways and mutation signature are distinct between two immune types.

Keywords: Stromal immunotype, Hepatocellular Carcinoma, prognosis., LASSO Cox regression, TCGA

Received: 01 May 2019; Accepted: 08 Jul 2019.

Edited by:

Alexandr Bazhin, Hospital of the University of Munich, Germany

Reviewed by:

William L. Redmond, Earle A. Chiles Research Institute, United States
Markus Schoenberg, Hospital of the University of Munich, Germany  

Copyright: © 2019 Li, Han, Yuan and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Wei Li, West China Hospital, Sichuan University, Chengdu, China, 13881958922@163.com
Mx. Hong Wu, West China Hospital, Sichuan University, Chengdu, China, 1136959464@qq.com