Journal of Hepatocellular Carcinoma (Mar 2022)

LRP1B is a Potential Biomarker for Tumor Immunogenicity and Prognosis of HCC Patients Receiving ICI Treatment

  • Cheng Y,
  • Tang R,
  • Li X,
  • Wang B,
  • Cheng Y,
  • Xiao S,
  • Sun P,
  • Yu W,
  • Li C,
  • Lin X,
  • Zhu Y

Journal volume & issue
Vol. Volume 9
pp. 203 – 220

Abstract

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Yang Cheng,1,2,* Rui Tang,1,* Xiangzhao Li,3 Biao Wang,4 Yanling Cheng,1 Shuzhe Xiao,1 Penghui Sun,5 Wenxuan Yu,2 Cheng Li,2 Xinsheng Lin,2 Yun Zhu2,* 1Digestive Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Liver Tumor Center, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 4Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 5Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun Zhu, Liver Tumor Center, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Email [email protected]: New predictors of the efficacy of hepatocellular carcinoma (HCC) immunotherapy are needed. The ability of a single gene mutation to predict the therapeutic effect of immune checkpoint inhibitors (ICI) in HCC remains unknown.Methods: The most frequently mutated genes in HCC were analyzed using the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Mutant genes that correlated with the tumor mutational burden (TMB) and prognosis were obtained. The mutation pattern and immunological function of one of the most frequently mutated genes, LRP1B, were determined. A pan-tumor analysis of LRP1B expression, association with cancer prognosis, and immunological role was also explored. A retrospective clinical study was conducted using 102 HCC patients who received ICI treatment to further verify whether gene mutations can predict the effectiveness of immunotherapy and prognosis of HCC.Results: LRP1B is among the most frequently mutated genes in HCC cohorts in TCGA and ICGC datasets. TCGA data showed that the LRP1B mutation activated immune signaling pathways and promoted mast cell activation. Patients with LRP1B mutations had significantly higher TMB than those with wild-type LRP1B. LRP1B expression correlated with the cancer-immunity cycle and immune cell infiltration. High LRP1B expression was also associated with poor survival among HCC patients. Results from the clinical study showed that HCC patients in the LRP1B mutation group had a poor response to ICI and worse prognosis than the wild-type group. The LRP1B mutation group had significantly higher TMB and mast cell infiltration in tumor tissues.Conclusion: This study is the first to report that a single gene LRP1B mutation is associated with a poor clinical response to ICI treatment and negative outcomes in HCC patients. HighLRP1B expression correlated with tumor immunity and HCC prognosis.Keywords: LRP1B mutation, ICI treatment response, prognosis, HCC, TMB

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