Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.
J Immunol Res. 2022 Jul 8;2022:9935705. doi: 10.1155/2022/9935705. eCollection 2022.
The hypoxic tumor microenvironment and long noncoding RNAs (lncRNAs) are pivotal in cancer progression and correlate with the survival outcome of patients. However, the role of hypoxia-related lncRNAs (HRLs) in colorectal cancer (CRC) development remains largely unknown. Herein, we developed a hypoxia-related lncRNA signature to predict patients' survival and immune infiltration. The RNA-sequencing data of 500 CRC patients were obtained from The Cancer Genome Atlas (TCGA) dataset, and HRLs were selected using Pearson's analysis. Next, the Cox regression analysis was applied to construct a risk signature consisting of 9 HRLs. This signature could predict the overall survival (OS) of CRC patients with high accuracy in training, validation, and entire cohort. This signature was an independent risk factor and exerted predictive ability in different subgroups. Functional analysis revealed different molecular features between high- and low-risk groups. A series of drugs including cisplatin showed different sensitivities between the two groups. The expression pattern of immune checkpoints was also distinct between the two clusters in this model. Furthermore, the high-risk group had higher immune, stromal, and ESTIMATE score and a more repressive immune microenvironment than the low-risk group. Moreover, MYOSLID, one of the lncRNAs in this signature, could significantly regulate the proliferation, invasion, and metastasis of CRC.
缺氧肿瘤微环境和长链非编码 RNA（lncRNA）在癌症进展中起着关键作用，与患者的生存结局相关。然而，缺氧相关 lncRNA（HRL）在结直肠癌（CRC）发展中的作用在很大程度上尚不清楚。在此，我们开发了一个缺氧相关 lncRNA 特征来预测患者的生存和免疫浸润。从癌症基因组图谱（TCGA）数据集获得了 500 例 CRC 患者的 RNA-seq 数据，并使用 Pearson 分析选择 HRL。接下来，应用 Cox 回归分析构建了一个由 9 个 HRL 组成的风险特征。该特征可以准确预测训练、验证和整个队列中 CRC 患者的总生存期（OS）。该特征是一个独立的危险因素，并在不同的亚组中具有预测能力。功能分析揭示了高低风险组之间不同的分子特征。一系列药物，包括顺铂，在两组之间表现出不同的敏感性。该模型中两个簇之间的免疫检查点表达模式也不同。此外，高风险组的免疫、基质和 ESTIMATE 评分以及更具抑制性的免疫微环境均高于低风险组。此外，该特征中 lncRNA 之一 MYOSLID 可以显著调节 CRC 的增殖、侵袭和转移。
