Development and Validation of a HAUS-Related Prognostic Signature in Liver Hepatocellular Carcinoma: A Multi-Omics Integration from Pan-Cancer Analysis to Single-Cell Resolution

  • J Hepatocell Carcinoma. 2026 May 22:13:598179. doi: 10.2147/JHC.S598179.
Yanli Liu  #  1  2 ,  Kang Liu  #  3 ,  Yang Ding  #  4 ,  Xiaodong Li  2 ,  Xuanxuan Shi  2 ,  Junrui Zhang  2 ,  Xiangyue Zhang  2 ,  Weiyao Peng  2 ,  Jingyi Deng  2 ,  Jingqi Chen  5
Affiliations
  • 1. Central Laboratory, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, People's Republic of China.
  • 2. State Key Laboratory of Respiratory Disease, The Second Clinical Medical School, Guangzhou Medical University, Guangzhou, Guangdong Province, People's Republic of China.
  • 3. School of Medicine, Chongqing University, Chongqing, People's Republic of China.
  • 4. School of Biomedical Engineering, Hainan University, Haikou, Hainan Province, People's Republic of China.
  • 5. Department of Oncology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, People's Republic of China.
  • # Contributed equally.
PMID: 42206070 DOI: 10.2147/JHC.S598179
Abstract

Background: The HAUS family proteins (HAUS1-HAUS8) are essential for mitotic spindle microtubule nucleation. Although HAUS dysregulation has been linked to tumor progression, whether these oncogenic functions are conserved or tissue-specific remains unclear. Therefore, a pan-cancer analysis is needed to identify universal HAUS drivers and context-dependent members for precision oncology.

Methods: We systematically evaluated the expression and prognostic significance of all eight HAUS genes across 33 Cancer types using TCGA data. Focusing on liver hepatocellular carcinoma (LIHC), we identified molecular subtypes based on HAUS co-expression patterns and characterized their associations with clinicopathological features, the tumor microenvironment (TME), immune checkpoint expression, and therapeutic response. A HAUS-related prognostic signature was developed using LASSO and COX regression analyses and validated in independent ICGC cohorts. Regulatory relationships among HAUS members and key signature genes were experimentally validated using immunohistochemistry and Western blotting.

Results: Most HAUS members were overexpressed across multiple cancers and correlated with poor clinical outcomes. In LIHC, two HAUS-based subtypes differed significantly in survival, clinicopathological profiles, immune features, mutational burden, stemness indices, and predicted therapeutic response. A prognostic signature comprising DTYMK and SPP1 effectively stratified LIHC patients into distinct risk groups, with the high-risk group showing significantly worse survival. A nomogram integrating the HAUS-related risk score with clinicopathological variables demonstrated strong predictive performance. Recombinant Osteopontin induced HAUS1 and DTYMK expression in LIHC cell lines, supporting a functional SPP1-HAUS1/DTYMK axis.

Conclusion: This study establishes the broad oncogenic relevance of HAUS genes across cancers and demonstrates that a HAUS-based signature enables prognostic stratification in LIHC.

Keywords
HAUS; drug sensitivity; liver hepatocellular carcinoma; microtubule nucleation; prognosis; tumor microenvironment.
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