CDCA8, a mitosis-related gene, as a prospective pan-cancer biomarker: implications for survival prognosis and oncogenic immunology

Hanjie Hu; Muhammad Umair; Sikandar Ali Khan; Aliya Irshad Sani; Sahar Iqbal; Fatima Khalid; Rizwana Sultan; Mostafa A Abdel-Maksoud; Ayman Mubarak; Turki M Dawoud; Abdul Malik; Ibrahim A Saleh; Abdul Aziz Al Amri; Norah Khaled Algarzae; Ahmad S Kodous; Yasir Hameed

doi:10.62347/WSEF7878

CDCA8, a mitosis-related gene, as a prospective pan-cancer biomarker: implications for survival prognosis and oncogenic immunology

Am J Transl Res. 2024 Feb 15;16(2):432-445. doi: 10.62347/WSEF7878. eCollection 2024.

Authors

Hanjie Hu¹, Muhammad Umair², Sikandar Ali Khan³, Aliya Irshad Sani⁴, Sahar Iqbal⁵, Fatima Khalid⁶, Rizwana Sultan⁷, Mostafa A Abdel-Maksoud⁸, Ayman Mubarak⁸, Turki M Dawoud⁸, Abdul Malik⁹, Ibrahim A Saleh¹⁰, Abdul Aziz Al Amri¹¹, Norah Khaled Algarzae¹², Ahmad S Kodous^{13

14}, Yasir Hameed¹⁵

Affiliations

¹ Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021, China.
² Department of Physiology, Gomal Medical College, MTI Dera Ismail Khan, Pakistan.
³ Department of Biochemistry Khyber Girls Medical College Peshawar, Pakistan.
⁴ Department of Biochemistry, Ziauddin Medical College Karachi 74700, Pakistan.
⁵ Department of Pathology, Azra Naheed Medical College Lahore 54000, Pakistan.
⁶ Department of Pathology, Al Aleem Medical College Lahore, Pakistan.
⁷ Department of Pathology, Faculty of Veterinary and Animal Sciences, Cholistan University of Veterinary and Animal Sciences Bahawalpur, Pakistan.
⁸ Department of Botany and Microbiology, College of Science, King Saud University P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁹ Department of Pharmaceutics, College of Pharmacy, King Saud University Saudi Arabia.
¹⁰ Faculty of Science, Zarqa University Zarqa 13110, Jordan.
¹¹ Biochemistry Department, College of Science, King Saud University P.O. Box 2455, Riyadh 11451, Saudi Arabia.
¹² Department of Physiology, College of Medicine, King Saud University Riyadh 11149, Saudi Arabia.
¹³ Radiation Biology Department, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic-Energy Authority (EAEA) Egypt.
¹⁴ Department of Molecular Oncology, Cancer Institute (WIA) 38, Sardar Patel Road, Chennai, P.O. Box 600036, Tamilnadu, India.
¹⁵ Department of Biotechnology, Institute of Biochemistry Biotechnology and Bioinformatics, The Islamia University of Bahawalpur Bahawalpur 63100, Pakistan.

Abstract

Background: Human cell division cycle-associated protein 8 (CDCA8), a critical regulator of mitosis, has been identified as a prospective prognostic biomarker in several cancer types, including breast, colon, and lung cancers. This study analyzed the diagnostic/prognostic potential and clinical implications of CDCA8 across diverse cancers.

Methods: Bioinformatics and molecular experiments.

Results: Analyzing TCGA data via TIMER2 and GEPIA2 databases revealed significant up-regulation of CDCA8 in 23 cancer types compared to normal tissues. Prognostically, elevated CDCA8 expression correlated with poorer overall survival in KIRC, LUAD, and SKCM, emphasizing its potential as a prognostic marker. UALCAN analysis demonstrated CDCA8 up-regulation based on clinical variables, such as cancer stage, race, and gender, in these cancers. Epigenetic exploration indicated reduced CDCA8 promoter methylation levels in Kidney Renal Clear Cell Carcinoma (KIRC), Lung Adenocarcinoma (LUAD), and Skin Cutaneous Melanoma (SKCM) tissues compared to normal controls. Promoter methylation and mutational analyses showcased a hypomethylation and low mutation rate for CDCA8 in these cancers. Correlation analysis revealed positive associations between CDCA8 expression and infiltrating immune cells, particularly CD8+ and CD4+ T cells. Protein-protein interaction (PPI) network analysis unveiled key interacting proteins, while gene enrichment analysis highlighted their involvement in crucial cellular processes and pathways. Additionally, exploration of CDCA8-associated drugs through DrugBank presented potential therapeutic options for KIRC, LUAD, and SKCM. In vitro validation using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) confirmed elevated CDCA8 expression in LUAD cell lines (A549 and H1299) compared to control cell lines (Beas-2B and NL-20).

Conclusion: This study provides concise insights into CDCA8's multifaceted role in KIRC, LUAD, and SKCM, covering expression patterns, diagnostic and prognostic relevance, epigenetic regulation, mutational landscape, immune infiltration, and therapeutic implications.

Keywords: CDCA8; biomarker; pan-cancer; prognosis; treatment.