Research Paper Advance Articles

Unveiling KLHL23 as a key immune regulator in hepatocellular carcinoma through integrated analysis

Liangliang Xu1,2, *, , Bo Li3, *, , Yuchen Liu4, *, , Zhengming Hu1, , Qing Dan1, , Bingxuan Xu1, , Hongjin Xiang1, , Yun Chen1, , Tingting Zheng1, , Desheng Sun1, , Li Liu1, ,

  • 1 Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Department of Ultrasound, Institute of Ultrasonic Medicine, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China China
  • 2 Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
  • 3 Guangdong-Hong Kong-Macau University Joint Laboratory of Digestive Cancer Research, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
  • 4 Guangdong Provincial Key Laboratory of Digestive Cancer Research, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, China
* Equal contribution and share first authorship

Received: February 10, 2024       Accepted: October 22, 2024       Published: December 4, 2024      

https://doi.org/10.18632/aging.206167
How to Cite

Copyright: © 2024 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Age-related cancers are characterized by impaired protein homeostasis, where Kelch protein superfamily members have showed accumulating clues as critical regulators. In this paper, the cancerous role of Kelch-like family member 23 (KLHL23) was comprehensively analyzed with TCGA and single cell GEO database across overall 33 cancer types. By multi-omics analysis upon the transcriptomic, genomic, and methylation data, the current study explored the association of KLHL23 with patient survival, gene ontology, tumor-infiltrating lymphocytes, and drug responses. The correlation of copy number variations and methylation with dysregulated expression of KLHL23 were also addressed. Notably, KLHL23 levels correlated with survival in cancers such as hepatocellular carcinoma and low-grade glioma. The study also highlighted how reduced KLHL23 expression is linked to increased immune activity and sensitivity to chemotherapy, suggesting its potential as a biomarker for cancer prognosis and treatment responsiveness.

Abbreviations

ACC: Adrenocortical carcinoma; BLCA: Bladder urothelial carcinoma; BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: Cholangiocarcinoma; COAD: Colon adenocarcinoma; DSS: Disease-specific survival; DFI: Disease-free interval; DLBC: Diffuse large B-cell lymphoma; ESCA: Esophageal carcinoma; EMT: Epithelial-mesenchymal transition; GBM: Glioblastoma multiforme; GEO: Gene Expression Omnibus; GSEA: Gene Set Enrichment Analysis; GO: Gene Ontology; HNSC: Head and neck squamous cell carcinoma; KICH: Kidney chromophobe; KIRC: Clear cell renal cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute myeloid leukemia; LGG: Lower-grade glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; MSigDB: Molecular Signatures Database; OS: Overall Survival; OV: Ovarian cancer; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and paraganglioma; PFI: Progression-free interval; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcoma; SKCM: Skin cutaneous melanoma; ssGSEA: Single-sample Gene Set Enrichment Analysis; STAD: Stomach adenocarcinoma; TCGA: The Cancer Genome Atlas; TGCT: Testicular germ cell tumors; THCA: Thyroid carcinoma; THYM: Thymoma; TILs: Tumor-infiltrating lymphocytes; UCEC: Uterine corpus endometrial carcinoma; UCS: Uterine carcinosarcoma; UVM: Uveal melanoma.