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A novel risk score system based on immune subtypes for identifying optimal mRNA vaccination population in hepatocellular carcinoma

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Abstract

Purpose

Although mRNA vaccines have shown certain clinical benefits in multiple malignancies, their therapeutic efficacies against hepatocellular carcinoma (HCC) remains uncertain. This study focused on establishing a novel risk score system based on immune subtypes so as to identify optimal HCC mRNA vaccination population.

Methods

GEPIA, cBioPortal and TIMER databases were utilized to identify candidate genes for mRNA vaccination in HCC. Subsequently, immune subtypes were constructed based on the candidate genes. According to the differential expressed genes among various immune subtypes, a risk score system was established using machine learning algorithm. Besides, multi-color immunofluorescence of tumor tissues from 72 HCC patients were applied to validate the feasibility and efficiency of the risk score system.

Results

Twelve overexpressed and mutated genes associated with poor survival and APCs infiltration were identified as potential candidate targets for mRNA vaccination. Three immune subtypes (e.g. IS1, IS2 and IS3) with distinct clinicopathological and molecular profiles were constructed according to the 12 candidate genes. Based on the immune subtype, a risk score system was developed, and according to the risk score from low to high, HCC patients were classified into four subgroups on average (e.g. RS1, RS2, RS3 and RS4). RS4 mainly overlapped with IS3, RS1 with IS2, and RS2+RS3 with IS1. ROC analysis also suggested the significant capacity of the risk score to distinguish between the three immune subtypes. Higher risk score exhibited robustly predictive ability for worse survival, which was further independently proved by multi-color immunofluorescence of HCC samples. Notably, RS4 tumors exhibited an increased immunosuppressive phenotype, higher expression of the twelve potential candidate targets and increased genome altered fraction, and therefore might benefit more from vaccination.

Conclusions

This novel risk score system based on immune subtypes enabled the identification of RS4 tumor that, due to its highly immunosuppressive microenvironment, may benefit from HCC mRNA vaccination.

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Data availability

All data generated and described in this article are available from the corresponding web servers, and are freely available to any scientist wishing to use them for noncommercial purposes, without breaching participant confidentiality. Further information is available on reasonable request from the corresponding author.

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Funding

This study was supported by National Natural Science Foundation of China (project NO.: 81972263, 82072714 and 82103221), the program of Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004), China Postdoctoral Science Foundation (2020M683094), the Science and Technology Program of Guangzhou (202201011427), the Excellent Young Talent Program of Guangdong Provincial People’s Hospital (KY012021190) and the High-level Hospital Construction Project (DFJH201921).

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Author notes

  1. Hongkai Zhuang, Chenwei Tang, Han Lin, and Zedan Zhang have contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Hongkai Zhuang, Chenwei Tang, Wentao Wang, Qingbin Wang, Wenliang Tan, Lei Yang, Zhiqin Xie, Bingkun Wang, Changzhen Shang & Yajin Chen

  2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510080, China

    Hongkai Zhuang, Chenwei Tang, Wentao Wang, Qingbin Wang, Wenliang Tan, Lei Yang, Zhiqin Xie, Bingkun Wang, Changzhen Shang & Yajin Chen

  3. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China

    Han Lin

  4. Department of Urology, Peking University First Hospital, Beijing, 100034, China

    Zedan Zhang

  5. Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, 516400, China

    Xinming Chen

  6. Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China

    Bo Chen

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  1. Hongkai Zhuang
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Contributions

Conceptualization: Z.H.K., C.B., C.Y.J., and S.C.Z.; Methodology: Z.H.K., T.C.W., L.H., and Z.Z.D.; Investigation: Z.H.K., and T.C.W.; Writing—Original Draft: Z.H.K., T.C.W., L.H., and Z.Z.D.; Writing—Review & Editing: Z.H.K., C.X.M., T.C.W., W.W.T., T.W.L., Y.L., X.Z.Q., W.B.K. and W.Q.B.; Visualization: Z.H.K.; Supervision: Z.H.K., C.B., C.Y.J., and S.C.Z.; Funding Acquisition: C.B., C.Y.J., S.C.Z., and T.W.L.

Corresponding authors

Correspondence to Bo Chen, Changzhen Shang or Yajin Chen.

Ethics declarations

Ethics approval and consent to participate

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All datasets are freely available as public resources. Therefore, local ethics approval was not required. Two tumor arrays with tumor and adjacent tumor samples from 90 HCC patients (HLivH180Su09-T-001 and HLivH180Su09-T-002) were purchased from Shanghai Outdo Biotech (Co. Ltd., Shanghai, China.). All tissues were collected according to the ethical standards from Shanghai Outdo Biotech (No.: SHYJS-CP-1607007). And informed consent was obtained from all participants.

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The authors declare no competing interests.

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Zhuang, H., Tang, C., Lin, H. et al. A novel risk score system based on immune subtypes for identifying optimal mRNA vaccination population in hepatocellular carcinoma. Cell Oncol. (2024). https://doi.org/10.1007/s13402-024-00921-1

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