ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(5):1234-1254. doi:10.7150/jca.91835 This issue Cite
Research Paper
Identification of novel T cell proliferation patterns, potential biomarkers and therapeutic drugs in colorectal cancer
1. Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China.
2. Department of Gastroenterology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, China.
3. Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China.
4. The Pathology Department of Anhui Medical University, Hefei 230032, Anhui, China.
5. Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, Anhui, China.
6. The First Affiliated Chuzhou Hospital of Anhui Medical University, Chuzhou 239000, Anhui, China.
#These authors have contributed equally to this work.
Abstract
Background: T cells are crucial components of antitumor immunity. A list of genes associated with T cell proliferation was recently identified; however, the impact of T cell proliferation-related genes (TRGs) on the prognosis and therapeutic responses of patients with colorectal cancer (CRC) remains unclear.
Methods: 33 TRG expression information and clinical information of patients with CRC gathered from multiple datasets were subjected to bioinformatic analysis. Consensus clustering was used to determine the molecular subtypes associated with T cell proliferation. Utilizing the Lasso-Cox regression, a predictive signature was created and verified in external cohorts. A tumor immune environment analysis was conducted, and potential biomarkers and therapeutic drugs were identified and confirmed via in vitro and in vivo studies.
Results: CRC patients were separated into two TRG clusters, and differentially expressed genes (DEGs) were identified. Patient information was divided into three different gene clusters, and the determined molecular subtypes were linked to patient survival, immune cells, and immune functions. Prognosis-associated DEGs in the three gene clusters were used to evaluate the risk score, and a predictive signature was developed. The ability of the risk score to predict patient survival and treatment response has been successfully validated using multiple datasets. To discover more possible biomarkers for CRC, the weighted gene co-expression network analysis algorithm was utilized to screen key TRG variations between groups with high- and low-risk. CDK1, BATF, IL1RN, and ITM2A were screened out as key TRGs, and the expression of key TRGs was confirmed using real-time reverse transcription polymerase chain reaction. According to the key TRGs, 7,8-benzoflavone was identified as the most significant drug molecule, and MTT, colony formation, wound healing, transwell assays, and in vivo experiments indicated that 7,8-benzoflavone significantly suppressed the proliferation and migration of CRC cells.
Conclusion: T cell proliferation-based molecular subtypes and predictive signatures can be utilized to anticipate patient results, immunological landscape, and treatment response in CRC. Novel biomarker candidates and potential therapeutic drugs for CRC were identified and verified using in vitro and in vivo tests.
Keywords: T cell proliferation, colorectal cancer, prognosis, tumor microenvironment, chemotherapy, immunotherapy
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