Proteomics Identifies LUC7L3 as a Prognostic Biomarker for Hepatocellular Carcinoma

Author:

Hou Yushan1,Wang Siqi1ORCID,Zhang Yiming1ORCID,Huang Xiaofen2,Zhang Xiuyuan1,He Fuchu13,Tian Chunyan12ORCID,Sun Aihua123

Affiliation:

1. State Key Laboratory of Medical Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing 102206, China

2. College of Life Sciences, Hebei University, Baoding 071002, China

3. Research Unit of Proteomics Dirven Cancer Precision Medicine, Chinese Academy of Medical Sciences, Beijing 102206, China

Abstract

Alternative splicing has been shown to participate in tumor progression, including hepatocellular carcinoma. The poor prognosis of patients with HCC calls for molecular classification and biomarker identification to facilitate precision medicine. We performed ssGSEA analysis to quantify the pathway activity of RNA splicing in three HCC cohorts. Kaplan–Meier and Cox methods were used for survival analysis. GO and GSEA were performed to analyze pathway enrichment. We confirmed that RNA splicing is significantly correlated with prognosis, and identified an alternative splicing-associated protein LUC7L3 as a potential HCC prognostic biomarker. Further bioinformatics analysis revealed that high LUC7L3 expression indicated a more progressive HCC subtype and worse clinical features. Cell proliferation-related pathways were enriched in HCC patients with high LUC7L3 expression. Consistently, we proved that LUC7L3 knockdown could significantly inhibit cell proliferation and suppress the activation of associated signaling pathways in vitro. In this research, the relevance between RNA splicing and HCC patient prognosis was outlined. Our newly identified biomarker LUC7L3 could provide stratification for patient survival and recurrence risk, facilitating early medical intervention before recurrence or disease progression.

Funder

National Key R&D Program of China

National Natural Science Foundation of China

National Science Foundation for Young Scientists of China

Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences

Specific Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine

Publisher

MDPI AG

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