Zhang Yingna, Yang Xiaofeng, Zhou Lisha, Gao Xiangting, Wu Xiangwei, Chen Xueling, Hou Jun, Wang Lianghai
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Sci Rep. 2022 Mar 11;12(1):4259. doi: 10.1038/s41598-022-08225-w.
Growing evidence has demonstrated the functional relevance of long intergenic noncoding RNAs (lincRNAs) to tumorigenesis and immune response. However, immune-related lincRNAs and their value in predicting the clinical outcomes of patients with liver cancer remain largely unexplored. Herein, we utilized the strategy of iterative gene pairing to construct a tumor-specific immune-related lincRNA pairs signature (IRLPS), which did not require specific expression levels, as an indicator of patient outcomes. The 18-IRLPS we developed was associated with overall survival, tumor progression, and recurrence in liver cancer patients. Multivariate analysis revealed that the risk model was an independent predictive factor. A high IRLPS risk was correlated suppressive immune microenvironment, and IRLPS-high patients might benefit more from CD276 blockade or TMIGD2 agonist. Patients in the high-risk group were associated with elevated tumor mutation, increased sensitivity to dopamine receptor antagonists, cisplatin, doxorubicin, and mitomycin but more resistance to vinblastine. Mechanistically, IRLPS high scores might lead to poor prognosis by promoting cell proliferation and metabolic reprogramming. The prognostic significance of the 18-IRLPS was confirmed in independent cancer datasets. These findings highlighted the robust predictive performances of the 18-IRLPS for prognosis and personalized treatment.
越来越多的证据表明长链基因间非编码RNA（lincRNA）与肿瘤发生和免疫反应具有功能相关性。然而，免疫相关的lincRNA及其在预测肝癌患者临床结局中的价值在很大程度上仍未被探索。在此，我们采用迭代基因配对策略构建了一种肿瘤特异性免疫相关lincRNA对特征（IRLPS），它不需要特定的表达水平，作为患者预后的一个指标。我们开发的18-IRLPS与肝癌患者的总生存期、肿瘤进展和复发相关。多变量分析显示风险模型是一个独立的预测因素。高IRLPS风险与免疫抑制微环境相关，IRLPS高的患者可能从CD276阻断或TMIGD2激动剂中获益更多。高危组患者与肿瘤突变增加、对多巴胺受体拮抗剂、顺铂、阿霉素和丝裂霉素的敏感性增加但对长春碱的耐药性更强有关。从机制上讲，IRLPS高分可能通过促进细胞增殖和代谢重编程导致预后不良。18-IRLPS的预后意义在独立的癌症数据集中得到证实。这些发现突出了18-IRLPS在预后和个性化治疗方面强大的预测性能。
