Shen Xin, Shang Lifeng, Han Junwei, Zhang Yi, Niu Wenkai, Liu Haiwang, Shi Hai
Department of Gastrointestinal Surgery, Xi'an Daxing Hospital, Xi'an, 71000, PR China.
Heliyon. 2024 Oct 11;10(23):e39260. doi: 10.1016/j.heliyon.2024.e39260. eCollection 2024 Dec 15.
Recently, immunotherapy has been recognized as an innovative treatment with great potential for patients with colon adenocarcinoma (COAD). Although the relationships between immune cells and immune substances are intricate and still unclear, some immune cells and substances could be considered prognostic factors for predicting therapeutic efficacy. To understand the genomic signatures of COAD related to CD8 T cells that could predict the prognosis of patients receiving immunotherapy and to discover new therapeutic targets, we conducted this study.
Data were gathered from the TCGA and GEO databases to assess the molecular features of CD8 T cells. We developed a CD8 T-cell score (CD8S) to quantify the population of CD8 T cells in each COAD patient. A thorough analysis of multilevel data was conducted to evaluate overall survival (OS), biological functions, immunological profiles, drug sensitivity, and responses to immunotherapy between the two groups defined by CD8S. Additionally, a series of in vitro experiments were executed to validate the reliability of the signatures associated with CD8 T cells.
CD8S has been shown to be a reliable prognostic factor for COAD according to different patient and subgroup analyses. Through in vitro experiments, we suggested that TSPYL2 may act as an oncogene in COAD. Through functional analysis, a high expression of genes linked to the cell cycle, cytoskeleton, cell adhesion, and various cancer-related pathways was observed in the high CD8S group, which aids in tumor invasion. Moreover, immune analysis reflected immunosuppression in patients with high CD8S. Patients in the low CD8S group were more sensitive to chemotherapy, targeted drugs, and immunotherapy due to higher genetic variants.
To better understand the biological characteristics and prognostic significance of CD8 T cells in immunotherapy for COAD, we thoroughly examined the molecular properties of CD8 T cells in COAD and developed a CD8 T-cell model.
近年来，免疫疗法已被公认为是一种对结肠腺癌（COAD）患者具有巨大潜力的创新疗法。尽管免疫细胞与免疫物质之间的关系错综复杂且仍不清楚，但一些免疫细胞和物质可被视为预测治疗效果的预后因素。为了了解与CD8 T细胞相关的COAD基因组特征，以预测接受免疫治疗患者的预后并发现新的治疗靶点，我们开展了本研究。
从TCGA和GEO数据库收集数据，以评估CD8 T细胞的分子特征。我们开发了一种CD8 T细胞评分（CD8S），以量化每位COAD患者的CD8 T细胞群体。对多级数据进行了全面分析，以评估由CD8S定义的两组之间的总生存期（OS）、生物学功能、免疫谱、药物敏感性和对免疫治疗的反应。此外，还进行了一系列体外实验，以验证与CD8 T细胞相关特征的可靠性。
根据不同的患者和亚组分析，CD8S已被证明是COAD的可靠预后因素。通过体外实验，我们认为TSPYL2可能在COAD中作为癌基因发挥作用。通过功能分析，在高CD8S组中观察到与细胞周期、细胞骨架、细胞粘附和各种癌症相关途径相关的基因高表达，这有助于肿瘤侵袭。此外，免疫分析反映了高CD8S患者的免疫抑制。低CD8S组的患者由于更高的基因变异，对化疗、靶向药物和免疫治疗更敏感。
为了更好地了解CD8 T细胞在COAD免疫治疗中的生物学特征和预后意义，我们全面研究了COAD中CD8 T细胞的分子特性，并建立了一个CD8 T细胞模型。
