Decoding the DSCC1 gene as a pan-cancer biomarker in human cancers via comprehensive multi-omics analyses

Jingru Wang; Sana Fatima Gilani; Nazia Noor; Muhammad Rashid Ahmed; Mehmooda Munazir; Ayesha Zubair; Rizwana Sultan; Mostafa A Abdel-Maksoud; Ibrahim A Saleh; Naser Zomot; Ahmad S Kodous; Shebl Salah Ibrahim; Mohamed A El-Tayeb; Mohammed Aufy; Mohamed Y Zaky; Syed Sairum Hassan; Yasir Hameed

doi:10.62347/YORR3755

Decoding the DSCC1 gene as a pan-cancer biomarker in human cancers via comprehensive multi-omics analyses

Am J Transl Res. 2024 Mar 15;16(3):738-754. doi: 10.62347/YORR3755. eCollection 2024.

Authors

Jingru Wang^{1

2}, Sana Fatima Gilani³, Nazia Noor⁴, Muhammad Rashid Ahmed⁵, Mehmooda Munazir⁶, Ayesha Zubair⁷, Rizwana Sultan⁸, Mostafa A Abdel-Maksoud⁹, Ibrahim A Saleh¹⁰, Naser Zomot¹⁰, Ahmad S Kodous^{11

12}, Shebl Salah Ibrahim¹³, Mohamed A El-Tayeb⁹, Mohammed Aufy¹⁴, Mohamed Y Zaky¹⁵, Syed Sairum Hassan¹⁶, Yasir Hameed¹⁷

Affiliations

¹ Mengcheng County Hospital of Chinese Medicine China.
² Bozhou Second Chinese Medicine Hospital China.
³ Department of Medicine, Sheikh Zayed Hospital Rahim Yar Khan, Pakistan.
⁴ Department of Pathology, Continental Medical College Lahore, Pakistan.
⁵ Department of Anatomy, Baqai Medical University Karachi, Pakistan.
⁶ Department of Botany, Government College Women University Sialkot, Pakistan.
⁷ Department of Biochemistry, CMH Lahore Medical College and Institute of Dentistry Lahore 54000, Punjab, Pakistan.
⁸ Department of Pathology, Faculty of Veterinary and Animal Sciences, Cholistan University of Veterinary and Animal Sciences Bahawalpur 63100, Punjab, Pakistan.
⁹ Department of Botany and Microbiology, College of Science, King Saud University P.O. Box 2455, Riyadh 11451, Saudi Arabia.
¹⁰ Faculty of Science, Zarqa University Zarqa 13110, Jordan.
¹¹ Department of Molecular Oncology, Cancer Institute (WIA) 38, Sardar Patel Road, P.O. Box 600036, Chennai, Tamilnadu, India.
¹² Department of Radiation Biology, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA) P.O. Box 13759, Cairo, Egypt.
¹³ Department of Biochemistry, College of Science, King Saud University P.O. Box 2455, Riyadh 11451, Saudi Arabia.
¹⁴ Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna Vienna 1090, Austria.
¹⁵ UPMC Hillman Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh Pittsburgh, PA 15213, USA.
¹⁶ Department of Medicine, Bilawal Medical College, Liaquat University of Medical and Health Sciences (LUMHS) Jamshoro 76090, Sindh, Pakistan.
¹⁷ Department of Biotechnology, Institute of Biochemistry, Biotechnology and Bioinformatics, The Islamia University of Bahawalpur Bahawalpur 63100, Punjab, Pakistan.

Abstract

Objectives: While dysregulation of DSCC1 (DNA Replication And Sister Chromatid Cohesion 1) has been established in breast cancer and colorectal cancer, its associations with other tumors remain unclear. Therefore, this study was launched to explore the role of DSCC1 in pan-cancer.

Methodology: In this study, we investigate the biological functions of DSCC1 across 33 solid tumors, elucidating its role in promoting oncogenesis and progression in various cancers through comprehensive analysis of multi-omics data.

Results: We conducted a comprehensive analysis of DSCC1 expression using RNA-seq data from TCGA and GTEx databases across 30 cancer types. Striking variations were observed, with significant overexpression of DSCC1 identified in numerous cancers. Elevated DSCC1 level was strongly associated with poorer prognosis, shorter survival, and advanced tumor stages in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), as indicated by Kaplan-Meier curves and GEPIA2 analysis. Further investigation into the molecular mechanisms revealed reduced DNA methylation in the DSCC1 promoter region in KIRP, LIHC, and LUAD, supporting enhanced RNA transcription. Protein expression analysis via the Human Protein Atlas (HPA) corroborated mRNA expression findings, showcasing elevated DSCC1 protein in KIRP, LIHC, and LUAD tissues. Mutational analysis using cBioPortal revealed alterations in 0.4% of KIRP, 17% of LIHC, and 5% of LUAD samples, predominantly characterized by amplification. Immune cell infiltration analysis demonstrated robust positive correlations between DSCC1 expression and CD8+ T cells, CD4+ T cells, and B cells, influencing the tumor microenvironment. STRING and gene enrichment analyses unveiled DSCC1's involvement in critical pathways, emphasizing its multifaceted impact. Notably, drug sensitivity analysis highlighted a significant correlation between DSCC1 mRNA expression and responses to 78 anticancer treatments, suggesting its potential as a predictive biomarker and therapeutic target for KIRP, LIHC, and LUAD. Finally, immunohistochemistry staining of clinical samples validated computational results, confirming elevated DSCC1 protein expression.

Conclusion: Overall, this study provides comprehensive insights into the pivotal role of DSCC1 in KIRP, LIHC, and LUAD initiation, progression, and therapeutic responsiveness, laying the foundation for further investigations and personalized treatment strategies.

Keywords: DSCC1; cancer; prognosis; treatment.