Yueh-Jung Wu, Chung-Chieh Chiao, Po-Kai Chuang, Chung-Bao Hsieh, Chou-Yuan Ko, Ching-Chung Ko, Chuan-Fa Chang, Tung-Yuan Chen, Ngoc Uyen Nhi Nguyen, Ching-Cheng Hsu, Tian-Huei Chu, Cheng-Chieh Fang, Hsuan-Yen Tsai, Hsien-Chun Tsai, Gangga Anuraga, Hoang Dang Khoa Ta, Do Thi Minh Xuan, Sachin Kumar, Sanskriti Dey, Fitria Sari Wulandari, Rosario Trijuliamos Manalu, Ngoc Phung Ly, Chih-Yang Wang, Yung-Kuo Lee
Recent advancements have elucidated the multifaceted roles of the Schlafen (SLFN) family, including SLFN5, SLFN11, SLFN12, SLFN13, and SLFN14, which are implicated in immunological responses. However, little is known about the roles of this gene family in relation to malignancy development. The current study aimed to explore the diagnostic and prognostic potential of Schlafen family genes in colorectal adenocarcinoma (COAD) through bioinformatics analysis. Leveraging advanced bioinformatics tools of bulk RNA-sequencing and single-cell sequencing, we conducted in-depth analyses of gene expressions, functional enrichment, and survival patterns of patients with colorectal cancer compared to normal tissue. Among Schlafen family genes, the transcription levels of SLFN5 in COAD tissues were significantly elevated and correlated with poor survival outcomes. Furthermore, SLFN5 regulated the immune response via Janus kinase (JAK)/signal transduction and activator of transcription (STAT)/interferon (IFN)-alpha/beta signaling. These chemokines in inflammation are associated with diabetes and metabolism, suggesting their involvement in altered cellular energetics for COAD progress. In addition, an immune cell deconvolution analysis indicated a correlation between SLFN5 expression and immune-related cell populations, such as regulatory T cells (Tregs). These findings highlighted the potential clinical significance of SLFN5 in COAD and provided insights into its involvement in the tumor microenvironment and immune regulation. Meanwhile, the drug discovery data of SFLN5 with potential targeted small molecules suggested its therapeutic potential for COAD. Collectively, the current research demonstrated that SFLN5 play crucial roles in tumor development and serve as a prospective biomarker for COAD. © The author(s).
Division of Colorectal Surgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung, 80284, Taiwan; Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 80424, Taiwan; Division of General Surgery, Department of Surgery, Tri-Service General Hospital, Taipei, 114202, Taiwan; Division of General Surgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung, 80284, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, 80284, Taiwan; Department of Medical Imaging, Chi-Mei Medical Center, Tainan, Taiwan; Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan; Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; Department of Internal Medicine, Division of Cardiology, The University of Texas Southwestern Medical Center, Dallas, 75390, TX, United States; Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, 80424, Taiwan; Medical Laboratory, Medical Education and Research Center, Kaohsiung Armed Forces General Hospital, Kaohsiung, 80284, Taiwan; Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taiwan; Department of Life Sciences, National University of Kaohsiung, Taiwan; Department of Statistics, Faculty of Science and Technology, PGRI Adi Buana University, East Java, Surabaya, 60234, Indonesia; Faculty of Pharmacy, Van Lang University, 69/68 Dang Thuy Tram Street, Ward 13, Binh Thanh District, Ho Chi Minh City, 70000, Viet Nam; Faculty of Biotechnology and Applied Sciences, Shoolini University of Biotechnology and Management Sciences, Himachal Pradesh, India; Department of Pharmacy, Faculty of Pharmacy, National Institute of Science and Technology, Jakarta, 12640, Indonesia; Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung, 25451, South Korea; Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology (UST), Seoul, 02792, South Korea
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