Research Paper Volume 16, Issue 2 pp 1879—1896
CDK16 as a potential prognostic biomarker correlated with an immunosuppressive tumor microenvironment and benefits in enhancing the effectiveness of immunotherapy in human cancers
- 1 Department of Urology, Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine, Shenzhen 518000, China
- 2 Department of Health Management, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410000, China
- 3 Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, China
Received: September 22, 2023 Accepted: December 14, 2023 Published: January 22, 2024
https://doi.org/10.18632/aging.205465How to Cite
Copyright: © 2024 Qi 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
Background: Cyclin-Dependent Kinase 16 (CDK16) plays significant biological roles in various diseases. Nonetheless, its function in different cancer types and its relationship with the Tumor Immune Microenvironment (TIME) are still not well-understood.
Methods: We analyzed the expression profile, genetic alterations, clinical features, and prognostic value of CDK16 in pan-cancer using data from The Cancer Genome Atlas, Genotype-Tissue Expression databases, and in vitro experiments. Additionally, the TIMER2 and ImmuCellAI databases were utilized to assess the correlation between CDK16 expression and immune cell infiltration levels. Finally, we examined the correlation between CDK16 and the response to immunotherapy using collected immunotherapy data.
Results: CDK16 is notably overexpressed in pan-cancer and is a risk factor for poor prognosis in various cancers. Our findings reveal that CDK16 regulates not only cell cycle-related functions to promote cell proliferation but also the autoimmunity-related functions of the innate and adaptive immune systems, along with other immune-related signaling pathways. Moreover, CDK16 overexpression contributes to an immunosuppressive tumor microenvironment, extensively suppressing immune-related features such as the expression of immune-related genes and pathways, as well as the count of immune-infiltrating cells. Our analysis indicated that individuals with low CDK16 expression showed higher response rates to immune checkpoint inhibitors and longer overall survival compared to those with high CDK16 expression.
Conclusions: This study establishes CDK16 as a potential biomarker for predicting poor prognosis in a wide range of cancers. Its role in shaping the immunosuppressive tumor microenvironment and influencing the efficacy of immunotherapy highlights the urgent need for developing targeted therapies against CDK16, offering new avenues for cancer treatment and management.
Abbreviations
AML: Acute myeloid leukemia; ACC: Adrenocortical carcinoma; BLCA: Bladder urothelial carcinoma; BRCA: Breast invasive carcinoma; CAFs: Cancer-associated fibroblasts; CHOL: Cholangiocarcinoma; COAD: Colon adenocarcinoma; CNV: Copy number variation; DFI: Disease-free interval; DSS: Disease-specific survival; ESCA: Esophageal squamous cell carcinoma; GSEA: Gene-set enrichment analysis; GBM: Glioblastoma multiforme; HNSC: Head and neck squamous cell carcinoma; ICIs: Immune checkpoint inhibitors; KICH: Kidney chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LIHC: Liver hepatocellular carcinoma; LGG: Lower grade glioma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; DLBC: Lymphoid neoplasm diffuse large B-cell lymphoma; MSI: Microsatellite instability; OS: Overall survival; OV: Ovarian serous cystadenocarcinoma; PCPG: Pheochromocytoma and paraganglioma; PRAD: Prostate adenocarcinoma; PFI: Progression-free interval; READ: Rectum adenocarcinoma; SSR3: Signal sequence receptor subunit 3; SKCM: Skin cutaneous melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular germ cell tumor; HPA: The Human Protein Atlas; THYM: Thymoma; THCA: Thyroid carcinoma; TAMs: Tumor-associated macrophages; TME: Tumor microenvironment; TIME: Tumor immune microenvironment; TMB: Tumor mutational burden; UCS: Uterine carcinosarcoma.