He Zikang, Liu Hongfeng, Guan Huilin, Ji Jinli, Jiang Ying, Zhang Naiwen, Song Zheyao, Wang Xingyun, Shen Ping, Wang Huan, Cui Rongjun
Department of Biochemistry and Molecular Biology, Mudanjiang Medical University, Mudanjiang, China.
Department of Scientific Research, Mudanjiang Medical University, Mudanjiang, China.
Front Oncol. 2022 Apr 27;12:812786. doi: 10.3389/fonc.2022.812786. eCollection 2022.
Digestive system pan-cancer is a general term for digestive system tumors including colorectal carcinoma (CRC), esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), and liver hepatocellular carcinoma (LIHC). Since the anatomical location, function and metabolism are closely related, there may be similarities in development and progression of these tumors. Hypoxia is the consequence of an imbalance between oxygen demand and supply, and intracellular hypoxia is associated with malignant progression, treatment resistance, and poor prognosis in tumors. Therefore, an urgent and challenging task is to investigate the molecular mechanisms associated with hypoxia in digestive system pan-cancer for the prognosis and treatment of digestive tract tumors. In this study, we identified 18 hypoxia-related lncRNAs (HRlncRNAs) by co-expression analysis between hypoxia genes and lncRNAs from digestive system pan-cancer. Six HRlncRNAs were then obtained using lasso regression and multivariate cox analysis to construct a prognostic model. Next, the Akaike information criterion (AIC) values for 3-year receiver operating curve (ROC) were counted to determine the cut-off point and establish an optimal model to distinguish between high- or low-risk groups among patients with digestive system pan-cancer. To evaluate the stability of the prognosis model, we validated it in terms of survival outcomes, clinicopathological stage, tumor-infiltrating immune cells, immune checkpoint inhibitors (ICIs) and anticancer drugs sensitivity. The results suggested that high- risk group had a worse prognosis and a more positive association with tumor-infiltrating immune cells such as B cells, cancer-associated fibroblasts, endothelial cells, monocytes, macrophages and bone marrow dendritic cells in digestive system pan-cancer. Immune checkpoint inhibitors (ICIs) related biomarkers discovered that high-risk group was positively correlated with high expression of HAVCR2 in digestive system pan-cancer. The anticancer drugs sensitivity analysis showed that the high-risk group was associated with the lower half-inhibitory centration (IC50) of Imatinib in digestive system pan-cancer. In conclusion, the prognostic model of HRlncRNAs showed a promising clinical prediction value and may provide a useful reference for the diagnosis and treatment of the digestive system tumors.
消化系统泛癌是包括结直肠癌（CRC）、食管癌（ESCA）、胃腺癌（STAD）和肝细胞癌（LIHC）在内的消化系统肿瘤的统称。由于解剖位置、功能和代谢密切相关，这些肿瘤在发生发展过程中可能存在相似性。缺氧是氧供需失衡的结果，细胞内缺氧与肿瘤的恶性进展、治疗抵抗及不良预后相关。因此，研究消化系统泛癌中与缺氧相关的分子机制以用于消化道肿瘤的预后和治疗是一项紧迫且具有挑战性的任务。在本研究中，我们通过对消化系统泛癌中缺氧基因与长链非编码RNA（lncRNA）进行共表达分析，鉴定出18个缺氧相关lncRNA（HRlncRNA）。随后使用套索回归和多变量cox分析获得6个HRlncRNA以构建预后模型。接下来，计算3年受试者工作特征曲线（ROC）的赤池信息准则（AIC）值以确定截断点，并建立一个最佳模型来区分消化系统泛癌患者中的高风险组和低风险组。为评估预后模型的稳定性，我们从生存结局、临床病理分期、肿瘤浸润免疫细胞、免疫检查点抑制剂（ICI）及抗癌药物敏感性等方面对其进行验证。结果表明，在消化系统泛癌中，高风险组预后较差，且与肿瘤浸润免疫细胞如B细胞、癌症相关成纤维细胞、内皮细胞、单核细胞、巨噬细胞和骨髓树突状细胞呈更显著的正相关。免疫检查点抑制剂（ICI）相关生物标志物发现，在消化系统泛癌中高风险组与HAVCR2的高表达呈正相关。抗癌药物敏感性分析表明，在消化系统泛癌中高风险组与伊马替尼的较低半数抑制浓度（IC50）相关。总之，HRlncRNA的预后模型显示出有前景的临床预测价值，可能为消化系统肿瘤的诊断和治疗提供有用的参考。
