Comprehensive landscape of gastric cancer-targeted therapy and identification of CSNK2A1 as a potential target
Liang Zhang,
Jiaqi Yang,
Yingpeng Huang,
Tao You,
Qunjia Huang,
Xian Shen,
Xiangyang Xue,
Shiyu Feng
Affiliations
Liang Zhang
Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China; Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer-Related Pathogens and Immunity, Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China
Jiaqi Yang
Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China
Yingpeng Huang
Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China
Tao You
Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China
Qunjia Huang
Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China
Xian Shen
Department of Gastrointestinal Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China
Xiangyang Xue
Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China; Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer-Related Pathogens and Immunity, Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China; Corresponding author. Microbiology and Immunology Laboratory, Basic Medicine College of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China.
Shiyu Feng
Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer-Related Pathogens and Immunity, Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China; Corresponding author. Microbiology and Immunology Laboratory, Basic Medicine College of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China.
Objective: To conduct a comprehensive analysis of the landscape of gastric cancer (GC)-targeted therapy clinical trials and identify potential therapeutic targets. Methods: A systematic search and analysis of the Cochrane Central Register of Controlled Trials (CENTRAL) was performed to retrieve all GC clinical trials published up to June 30, 2022. Approved therapeutic targets for 11 common cancers were compiled and analyzed. The role of CSNK2A1 in GC was investigated using bioinformatics tools such as GEPIA, KMPLOT, SangerBox, STRING, ACLBI, and TIMER. Four gastric cancer cell lines (AGS, HGC, MGC, BGC) and one normal gastric mucosa cell line (GES-1) were utilized to assess the sensitivity to the CSNK2A1 inhibitor CX-4945. Quantitative real-time polymerase chain reaction (qPCR) was employed to quantify the cellular expression of CSNK2A1. Cellular apoptosis was evaluated using flow cytometry and Western blot analysis. Results: The failure rate of GC randomized controlled clinical trials (RCTs) was strikingly high, accounting for 74.29 % (26/35) of the trials. Among the 35 approved targets in 11 different cancers, 13 targets were rigorously evaluated and identified as potential therapeutic targets for GC. Bioinformatics analysis revealed that CSNK2A1 is closely associated with multiple biological characteristics in GC, and its increased expression correlated significantly with enhanced sensitivity to CX-4945 treatment. Flow cytometry and Western blot analysis consistently demonstrated concentration-dependent apoptosis induced by CX-4945 in GC cell lines. Conclusions: The high failure rate of GC clinical trials highlights the need for a more scientific and precise approach in target identification and clinical trial design. CSNK2A1 emerges as a promising therapeutic target for GC, and its expression level could potentially serve as a biomarker for predicting sensitivity to CX-4945 treatment. Further research is warranted to elucidate the underlying molecular mechanisms and validate the clinical significance of CSNK2A1 in GC therapy.
