Wang Jun, Wang Beidi, Zhou Biting, Chen Jing, Qi Jia, Shi Le, Yu Shaojun, Chen Guofeng, Kang Muxing, Jin Xiaoli, Wang Lie, Xu Jinghong, Zhu Linghua, Chen Jian
Department of Gastroenterology Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China.
Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China.
Cancer Cell Int. 2022 Feb 10;22(1):69. doi: 10.1186/s12935-022-02493-2.
Gastric cancer (GC), the most commonly diagnosed cancer worldwide with poor 5-year survival rate in advanced stages. Although immune-related and survival-related biomarkers, which typically comprise aberrantly expressed long non-coding RNAs (lncRNAs) and genes, have been identified, there are no reports of immune-related lncRNA pair (IRLP) signatures for GC.
In this study, we acquired lncRNA expression profiles from The Cancer Genome Atlas (TCGA) and used the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards model (iteration = 1000) to develop a IRLP prognostic signature. The area under curve (AUC) was used to assess the prognosis predictive power. The multivariate Cox regression analysis was performed to identify whether this signature was an independent prognostic factor. The immune cell infiltration analysis was performed between the two risk groups. Last, molecular experiments were performed to explore LINC01082 is involved in the development of GC.
We acquired lncRNA expression profiles and used the LASSO Cox model to develop an 18-IRLP signature with a strong prognostic predictive power. The 5-year AUC values of the training, validation, and overall TCGA datasets were 0.77, 0.86, and 0.80, respectively. The different prognostic outcomes between the high- and low-risk groups were determined using our 18-IRLP signature. Moreover, our 18-IRLP signature was an independent prognostic factor as per the multivariate Cox regression analysis, and showed better prognostic evaluation than the traditional TNM staging system as well as other clinical features. We also found differences in cancer-associated fibroblast and macrophage M2 infiltration and the expression of PD-L1, CTLA4, LAG3, and HLA were also observed between the two risk groups (P < 0.05). Analysis of biological functions revealed that target genes of the lncRNAs in the IRLP signature were enriched in focal adhesion and regulation of actin cytoskeleton. Finally, as one of significant candidates of IRLP signature, overexpression of LINC01082 suppressed the invasion ability of GC cells as well as PD-L1 expression profiles.
Our novel 18-IRLP signature provides new insights regarding immunological biomarkers, imparts a better understanding of the tumor immune microenvironment, and can be used for predicting prognosis and evaluating immune response in GC.
胃癌（GC）是全球最常被诊断出的癌症，晚期患者的5年生存率较低。尽管已经确定了与免疫相关和与生存相关的生物标志物，这些标志物通常包括异常表达的长链非编码RNA（lncRNA）和基因，但尚无关于胃癌免疫相关lncRNA对（IRLP）特征的报道。
在本研究中，我们从癌症基因组图谱（TCGA）获取lncRNA表达谱，并使用最小绝对收缩和选择算子（LASSO）Cox比例风险模型（迭代次数 = 1000）来开发IRLP预后特征。曲线下面积（AUC）用于评估预后预测能力。进行多变量Cox回归分析以确定该特征是否为独立的预后因素。在两个风险组之间进行免疫细胞浸润分析。最后，进行分子实验以探索LINC01082是否参与胃癌的发生发展。
我们获取了lncRNA表达谱，并使用LASSO Cox模型开发了具有强大预后预测能力的18-IRLP特征。训练集、验证集和整个TCGA数据集的5年AUC值分别为0.77、0.86和0.80。使用我们的18-IRLP特征确定了高风险组和低风险组之间不同的预后结果。此外，根据多变量Cox回归分析，我们的18-IRLP特征是一个独立的预后因素，并且比传统的TNM分期系统以及其他临床特征显示出更好的预后评估。我们还发现两个风险组之间在癌症相关成纤维细胞和巨噬细胞M2浸润方面存在差异，并且观察到PD-L1、CTLA4、LAG3和HLA的表达也存在差异（P < 0.05）。生物学功能分析表明，IRLP特征中lncRNA的靶基因在粘着斑和肌动蛋白细胞骨架调节方面富集。最后，作为IRLP特征的重要候选者之一，LINC01082的过表达抑制了胃癌细胞的侵袭能力以及PD-L1表达谱。
我们新的18-IRLP特征为免疫生物标志物提供了新的见解，有助于更好地理解肿瘤免疫微环境，并可用于预测胃癌的预后和评估免疫反应。
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