Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Laboratory of Digestive Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Biosci Rep. 2022 Sep 30;42(9). doi: 10.1042/BSR20220989.
The combination of docetaxel, cisplatin, and S-1 (DCS) is a common chemotherapy regimen for patients with gastric cancer (GC). However, studies on long noncoding RNAs (lncRNAs) associated with the chemotherapeutic response to and prognosis after DCS remain lacking. The aim of the present study was to identify DCS mRNAs-lncRNAs associated with chemotherapy response and prognosis in GC patients. In the present study, we identified 548 lncRNAs associated with these 16 mRNAs in the TCGA and GSE31811 datasets. Eleven lncRNAs were used to construct a prognostic signature by least absolute shrinkage and selection operator (LASSO) regression. A model including the 11 lncRNAs (LINC02532, AC007277.1, AC005324.4, AL512506.1, AC068790.7, AC022509.2, AC113139.1, LINC00106, AC005165.1, MIR100HG, and UBE2R2-AS1) associated with the prognosis of GC was constructed. The signature was validated in the TCGA database, model comparison, and qRT-PCR experiments. The results showed that the risk signature was a more effective prognostic factor for GC patients. Furthermore, the results showed that this model can well predicting chemotherapy drug response and immune infiltration of GC patients. In addition, our experimental results indicated that lower expression levels of LINC00106 and UBE2R2-AS1 predicted worse drug resistance in AGS/DDP cells. The experimental results agreed with the predictions. Furthermore, knockdown of LINC00106 or UBE2R2-AS1 can significantly enhanced the proliferation and migration of GC AGS cells in vitro. In conclusion, a novel DCS therapy-related lncRNA signature may become a new strategy to predict chemotherapy response and prognosis in GC patients. LINC00106 and UBE2R2-AS1 may exhibit a tumor suppressive function in GC.
多西他赛、顺铂和 S-1（DCS）联合治疗是胃癌（GC）患者常用的化疗方案。然而，关于与 DCS 化疗反应和预后相关的长链非编码 RNA（lncRNA）的研究仍然缺乏。本研究旨在鉴定与 GC 患者 DCS 化疗反应和预后相关的 DCS mRNAs-lncRNAs。在本研究中，我们在 TCGA 和 GSE31811 数据集鉴定了 548 个与这些 16 个 mRNA 相关的 lncRNA。采用最小绝对值收缩和选择算子（LASSO）回归构建了包含 11 个 lncRNA 的预后模型。包括 11 个 lncRNA（LINC02532、AC007277.1、AC005324.4、AL512506.1、AC068790.7、AC022509.2、AC113139.1、LINC00106、AC005165.1、MIR100HG 和 UBE2R2-AS1）的 GC 预后模型构建。在 TCGA 数据库、模型比较和 qRT-PCR 实验中验证了该模型。结果表明，该模型是 GC 患者更有效的预后因素。此外，该模型可以很好地预测 GC 患者的化疗药物反应和免疫浸润。此外，我们的实验结果表明，LINC00106 和 UBE2R2-AS1 的低表达水平预示着 AGS/DDP 细胞对药物的耐药性更差。实验结果与预测一致。此外，下调 LINC00106 或 UBE2R2-AS1 可以显著增强 GC AGS 细胞在体外的增殖和迁移。综上所述，一种新的 DCS 治疗相关 lncRNA 标志可能成为预测 GC 患者化疗反应和预后的新策略。LINC00106 和 UBE2R2-AS1 在 GC 中可能发挥肿瘤抑制功能。
