Xiao Yu, Zhou Han, Chen Yiran, Liu Libin, Wu Qian, Li Hui, Lin Peicheng, Li Jinluan, Wu Junxin, Tang Lirui
Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Front Genet. 2023 May 30;14:1186862. doi: 10.3389/fgene.2023.1186862. eCollection 2023.
Anoikis is a type of apoptosis associated with cell detachment. Resistance to anoikis is a focal point of tumor metastasis. This study aimed to explore the relationship among anoikis-related genes (ARGs), immune infiltration, and prognosis in colorectal cancer (CRC). The transcriptome profile and clinical data on patients with CRC were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Patients were divided into two clusters based on the expression of ARGs. Differences between the two ARG molecular subtypes were analyzed in terms of prognosis, functional enrichment, gene mutation frequency, and immune cell infiltration. An ARG-related prognostic signature for predicting overall survival in patients with CRC was developed and validated using absolute value convergence and selection operator (LASSO) regression analysis. The correlation between the signature risk score and clinicopathological features, immune cell infiltration, immune typing, and immunotherapy response was analyzed. The risk score combined with clinicopathological characteristics was used to construct a nomogram to assess CRC patients' prognosis. Overall, 151 ARGs were differentially expressed in CRC. Two ARG subtypes, namely, ARG-high and ARG-low groups, were identified and correlated with CRC prognosis. The gene mutation frequency and immune, stromal, and ESTIMATE scores of the ARG-high group were higher than those of the ARG-low group. Moreover, CD8, natural killer cells, M1 macrophages, human leukocyte antigen (HLA), and immune checkpoint-related genes were significantly increased in the ARG-high group. An optimized 25-gene CRC prognostic signature was successfully constructed, and its prognostic predictive ability was validated. The high-risk score was correlated with T, N, M, and TNM stages. Risk scores were negatively correlated with dendritic cells, eosinophils, and CD4 cells, and significantly positively correlated with regulatory T cells. Patients in the high-risk group were more likely to exhibit immune unresponsiveness. Finally, the nomogram model was constructed and showed good prognostic predictive power. ARGs are associated with clinicopathological features and the prognosis of CRC, and play important roles in the immune microenvironment. Herein, we underpinned the usefulness of ARGs in CRC to develop more effective immunotherapy techniques.
失巢凋亡是一种与细胞脱离相关的细胞凋亡类型。对失巢凋亡的抗性是肿瘤转移的一个焦点。本研究旨在探讨结直肠癌（CRC）中失巢凋亡相关基因（ARG）、免疫浸润和预后之间的关系。从癌症基因组图谱和基因表达综合数据库中检索CRC患者的转录组谱和临床数据。根据ARG的表达将患者分为两个簇。从预后、功能富集、基因突变频率和免疫细胞浸润方面分析了两种ARG分子亚型之间的差异。使用绝对值收敛和选择算子（LASSO）回归分析开发并验证了一种用于预测CRC患者总生存期的ARG相关预后特征。分析了特征风险评分与临床病理特征、免疫细胞浸润、免疫分型和免疫治疗反应之间的相关性。风险评分与临床病理特征相结合用于构建列线图以评估CRC患者的预后。总体而言，151个ARG在CRC中差异表达。鉴定出两种ARG亚型，即ARG高表达组和ARG低表达组，且它们与CRC预后相关。ARG高表达组的基因突变频率以及免疫、基质和ESTIMATE评分均高于ARG低表达组。此外，ARG高表达组中的CD8、自然杀伤细胞、M1巨噬细胞、人类白细胞抗原（HLA）和免疫检查点相关基因显著增加。成功构建了一个优化的25基因CRC预后特征，并验证了其预后预测能力。高风险评分与T、N、M和TNM分期相关。风险评分与树突状细胞、嗜酸性粒细胞和CD4细胞呈负相关，与调节性T细胞呈显著正相关。高风险组患者更易表现出免疫无反应性。最后，构建了列线图模型，其显示出良好的预后预测能力。ARG与CRC的临床病理特征和预后相关，并在免疫微环境中发挥重要作用。在此，我们证实了ARG在CRC中对于开发更有效的免疫治疗技术的有用性。
