Colorectal cancer (CRC) is a common and highly lethal gastrointestinal malignancy. Immunotherapy has shown positive efficacy in the treatment of CRC; however, only a minority of patients benefit from immunotherapy. The aim of this study is to construct a cuproptosis-related lncRNA (CRLs) risk score model to predict the prognosis and immune infiltration of CRC patients. Firstly, we synthetically analyzed 19 cuproptosis-related genes (CRGs) from CRC samples derived from the TCGA and obtained 33 CRLs that were significantly associated with prognosis. Next, we defined three cuproptosis modification patterns via consensus clustering analysis (C1, C2, and C3). Further analysis showed that there were significant differences in the abundance of B cells, NK cells, fibroblasts, monocytes, CD8⁺ cells, bone marrow dendritic cells, and cytotoxic lymphocytes in different clusters. In addition, the LASSO regression screened out 6 individual CRLs (AC009315.1, PLS3-AS1, ZEB1-AS1, AC007608.3, AC010789.2, and AC010207.1) closely related to the prognosis of CRC. We found that the low-risk group had better survival prognoses in patients. Furthermore, the high-risk group had lower immune scores and exhibited lower CD8⁺ T cell infiltration. Moreover, the low-risk group had lower immune exclusion, immune dysfunction and TIDE scores than the high-risk group. Interestingly, the lncRNAs in our risk model were positively associated with most immune checkpoints. CD274 (PD-L1), CTLA4, and HAVCR2 (TIM3) were positively correlated with risk scores. Moreover, MSI-H patients had lower risk scores than MSI-L patients, and IPS scores were significantly higher in the low CRLs score group. In conclusion, we constructed a novel risk score model with6 lncRNAs related to cuproptosis, which may be a potential biomarker for evaluating the prognosis and immune treatment for CRC.

中文翻译：

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基于Cuproptosis相关lncRNAs构建预测结直肠癌预后和对免疫治疗反应的预后模型

结直肠癌 (CRC) 是一种常见且高度致命的胃肠道恶性肿瘤。免疫疗法在 CRC 的治疗中显示出积极的疗效；然而，只有少数患者受益于免疫疗法。本研究的目的是构建与铜细胞凋亡相关的 lncRNA (CRLs) 风险评分模型，以预测 CRC 患者的预后和免疫浸润。首先，我们综合分析了来自 TCGA 的 CRC 样本中的 19 个铜凋亡相关基因 (CRG)，并获得了 33 个与预后显着相关的 CRL。接下来，我们通过共识聚类分析（C1、C2 和 C3）定义了三种铜细胞凋亡修饰模式。^{进一步分析显示，B细胞、NK细胞、成纤维细胞、单核细胞、CD8 +}的丰度存在显着差异细胞、骨髓树突状细胞和不同簇的细胞毒性淋巴细胞。此外，LASSO回归筛选出6个与CRC预后密切相关的个体CRL（AC009315.1、PLS3-AS1、ZEB1-AS1、AC007608.3、AC010789.2和AC010207.1）。我们发现低风险组患者的生存预后更好。此外，高风险组的免疫评分较低，CD8 ^{+表现也较低}T 细胞浸润。此外，低风险组的免疫排斥、免疫功能障碍和 TIDE 评分低于高风险组。有趣的是，我们风险模型中的 lncRNA 与大多数免疫检查点呈正相关。CD274 (PD-L1)、CTLA4 和 HAVCR2 (TIM3) 与风险评分呈正相关。此外，MSI-H 患者的风险评分低于 MSI-L 患者，而 IPS 评分在低 CRLs 评分组中显着更高。总之，我们构建了一个新的风险评分模型，其中包含 6 个与铜细胞凋亡相关的 lncRNA，这可能是评估 CRC 预后和免疫治疗的潜在生物标志物。