College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar.
Human Immunology Division, Research Branch, Sidra Medicine, Doha, Qatar.
J Transl Med. 2022 Sep 30;20(1):442. doi: 10.1186/s12967-022-03654-7.
Advances in our understanding of the tumor microenvironment have radically changed the cancer field, highlighting the emerging need for biomarkers of an active, favorable tumor immune phenotype to aid treatment stratification and clinical prognostication. Numerous immune-related gene signatures have been defined; however, their prognostic value is often limited to one or few cancer types. Moreover, the area of non-coding RNA as biomarkers remains largely unexplored although their number and biological roles are rapidly expanding.
We developed a multi-step process to identify immune-related long non-coding RNA signatures with prognostic connotation in multiple TCGA solid cancer datasets.
Using the breast cancer dataset as a discovery cohort we found 2988 differentially expressed lncRNAs between immune favorable and unfavorable tumors, as defined by the immunologic constant of rejection (ICR) gene signature. Mapping of the lncRNAs to a coding-non-coding network identified 127 proxy protein-coding genes that are enriched in immune-related diseases and functions. Next, we defined two distinct 20-lncRNA prognostic signatures that show a stronger effect on overall survival than the ICR signature in multiple solid cancers. Furthermore, we found a 3 lncRNA signature that demonstrated prognostic significance across 5 solid cancer types with a stronger association with clinical outcome than ICR. Moreover, this 3 lncRNA signature showed additional prognostic significance in uterine corpus endometrial carcinoma and cervical squamous cell carcinoma and endocervical adenocarcinoma as compared to ICR.
We identified an immune-related 3-lncRNA signature with prognostic connotation in multiple solid cancer types which performed equally well and in some cases better than the 20-gene ICR signature, indicating that it could be used as a minimal informative signature for clinical implementation.
对肿瘤微环境的认识的进步彻底改变了癌症领域，凸显出需要寻找具有活跃有利肿瘤免疫表型的生物标志物来辅助治疗分层和临床预后判断。已经定义了许多与免疫相关的基因特征；然而，它们的预后价值通常局限于一种或几种癌症类型。此外，非编码 RNA 作为生物标志物的领域在很大程度上仍未得到探索，尽管它们的数量和生物学作用正在迅速扩大。
我们开发了一种多步骤流程，用于在多个 TCGA 实体癌数据集识别具有预后含义的免疫相关长非编码 RNA 特征。
我们使用乳腺癌数据集作为发现队列，发现了 2988 个在免疫有利和不利肿瘤之间差异表达的 lncRNA，这些肿瘤是根据免疫排斥常数 (ICR) 基因特征定义的。将 lncRNA 映射到编码-非编码网络，确定了 127 个与免疫相关疾病和功能相关的编码蛋白基因的代理。接下来，我们定义了两个不同的 20-lncRNA 预后特征，在多种实体癌中，这两个特征在总生存期方面的影响比 ICR 特征更强。此外，我们发现了一个 3 lncRNA 特征，在 5 种实体癌中具有预后意义，与 ICR 相比与临床结果的关联更强。此外，与 ICR 相比，该 3 lncRNA 特征在子宫体子宫内膜癌、宫颈鳞状细胞癌和宫颈内膜腺癌中具有额外的预后意义。
我们在多种实体癌类型中发现了一个具有免疫相关 3-lncRNA 特征的预后特征，其性能与 20 基因 ICR 特征相当，在某些情况下甚至更好，这表明它可作为临床实施的最小信息特征。
