A prognostic and immunological analysis of 7B-containing Kelch structural domain (KLHDC7B) in pan-cancer: a potential target for immunotherapy and survival

• Published in: Journal of cancer research and clinical oncology Vol. 149; no. 10; pp. 7857 - 7876
• Main Authors: Ding, Jiatong, Ji, Xunhui, Liu, Lanqi, Chen, De-Zhi, Luo, Nan, Yu, Xiao-Ting, Guo, Fei
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2023; Springer Nature B.V
• Subjects: Cancer; Cancer Research; Carcinogenesis; Correlation analysis; Cytoskeleton; DNA methylation; Gene expression; Genetic diversity; Genomes; Hematology; Humans; Immune checkpoint; Immune response; Immunology; Immunotherapy; Infiltration; Internal Medicine; Kelch Repeat; Medicine; Medicine & Public Health; Metastases; Microsatellite Instability; Neoplasms - genetics; Neoplasms - therapy; Oncology; Prognosis; Suppressor cells; Survival analysis; Tumorigenesis; Biomarker; Prognosis; Tumor immunity; KLHDC7B; Pan-cancer
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-023-04738-7

Purpose KLHDC7B is a member of Kelch family, with a Kelch domain in the C-terminal half, which plays a role in various cellular events, such as cytoskeletal arrangement, protein degradation, gene expression. Although there is increasing evidence supporting KLHDC7B's vital role in tumorigenesis, a systematic analysis of KLHDC7B in cancers remains lacking. Therefore, we intended to investigate the prognostic value for KLHDC7B across 33 cancer types and explore its potential immunological function. Methods GEO (Gene Expression Omnibus database) and TCGA (The Cancer Genome Atla) database were used to explore the role of KLHDC7B in 33 cancers. TIMER2, GEPIA2 and Kaplan–Meier plotter were utilized to explore the KLHDC7B expression level and prognostic value in different cancers. The pan cancer genetic variation and DNA methylation of KLHDC7B were analyzed by cBioPortal and MEXPRESS. TIMER2 was employed to investigate the correlation between KLHDC7B expression and immune infiltration. The relationship of KLHDC7B expression with TMB (tumor mutational burden) and MSI (microsatellite instability) were evaluated using Spearman correlation analysis. Finally, by GO and KEGG enrichment analysis, the underlying mechanisms of KLHDC7B in tumor pathophysiology were further investigated. Results KLHDC7B expression level was related to pathological stages, MSI, TMB, immune checkpoint and immune cell infiltration in most cancers. Especially, we found that the KLHDC7B expression was negatively correlated with the immune infiltration of Myeloid derived suppressor cells into TGCT and GBM. Additionally, survival analysis showed that the expression of KLHDC7B was connected with overall survival (OS) in 3 cancers and disease-free survival (DFS) in 5 cancers. Furthermore, the enrichment analysis revealed that the KLHDC7B collecting genes and binding proteins are related to the function of proteins and immune response. Conclusion KLHDC7B demonstrates strong clinical utility as markers of prognostic and immune response in pan-cancer.