Cai Xiao-Xia, Chen Guo-Ming, Zheng Zi-Qi, Yin Yi-Xin, Wang Shuang, Qiao Li, Chen Xiao-Jiang, Zhao Bai-Wei, Duan Jin-Ling, Liang Cheng-Cai, Zhang Ruo-Peng, Wei Cheng-Zhi, Zhang Fei-Yang, Huang Bo-Wen, Liu Ze-Xian, Zhou Zhi-Wei, Xie Dan, Cai Mu-Yan, Yuan Shu-Qiang, Li Yuan-Fang, Nie Run-Cong
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Mol Cancer. 2024 Dec 30;23(1):284. doi: 10.1186/s12943-024-02196-4.
Long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) progression and metastasis. However, research comprehensively exploring tissue-derived lncRNAs for predicting peritoneal recurrence in patients with GC remains limited. This study aims to investigate the transcriptional landscape of lncRNAs in GC with peritoneal metastasis (PM) and to develop an integrated lncRNA-based score to predict peritoneal recurrence in patients with GC after radical gastrectomy.
We analyzed the transcriptome profile of lncRNAs in paired peritoneal, primary gastric tumor, and normal tissue specimens from 12 patients with GC in the Sun Yat-sen University Cancer Center (SYSUCC) discovery cohort. Key lncRNAs were identified via interactive analysis with the TCGA database and SYSUCC validation cohort. A score model was constructed using the LASSO regression model and nomogram COX regression and evaluated using receiver operating characteristic curves. The role of lncRNAs in the PM of GC was then examined through wound healing, Transwell, 3D multicellular tumor spheroid invasion, and peritoneal cavity xenograft tumorigenicity assays in mice.
Five essential lncRNAs were screened and incorporated into the PM risk score to predict peritoneal recurrence-free survival (pRFS). We developed a comprehensive, integrated nomogram score, including the PM risk score, pT, pN, and tumor size, which could effectively predict the 5-year pRFS with an Area under the curve of 0.79 (95% CI: 0.71-0.88). Subsequently, we demonstrated that one of these lncRNAs, CASC15, promoted the invasion and migration of GC cells in vitro and facilitated the PM of GC cells in vivo, initially verifying that lncRNAs contribute to the PM of GC. Mechanistic analysis demonstrated that CASC15 promoted EMT and metastasis by activating the JNK and p38 pathways.
A lncRNA-based integrated score was constructed in this study to predict peritoneal recurrence in patients clinically.
长链非编码RNA（lncRNA）在胃癌（GC）的进展和转移中起关键作用。然而，全面探索组织来源的lncRNA以预测GC患者腹膜复发的研究仍然有限。本研究旨在调查伴有腹膜转移（PM）的GC中lncRNA的转录图谱，并开发一种基于lncRNA的综合评分系统，以预测根治性胃切除术后GC患者的腹膜复发情况。
我们分析了来自中山大学肿瘤防治中心（SYSUCC）发现队列的12例GC患者的配对腹膜、原发性胃肿瘤和正常组织标本中lncRNA的转录组图谱。通过与TCGA数据库和SYSUCC验证队列的交互分析确定关键lncRNA。使用LASSO回归模型和列线图COX回归构建评分模型，并通过受试者工作特征曲线进行评估。然后通过小鼠伤口愈合、Transwell、3D多细胞肿瘤球体侵袭和腹腔异种移植致瘤性试验，研究lncRNA在GC腹膜转移中的作用。
筛选出5个关键lncRNA并将其纳入PM风险评分系统，以预测无腹膜复发生存期（pRFS）。我们开发了一个综合的列线图评分系统，包括PM风险评分、pT、pN和肿瘤大小，其曲线下面积为0.79（95%CI：0.71-0.88），能够有效预测5年pRFS。随后，我们证明这些lncRNA之一CASC15在体外促进GC细胞的侵袭和迁移，并在体内促进GC细胞的腹膜转移，初步验证了lncRNA对GC腹膜转移的作用。机制分析表明，CASC15通过激活JNK和p38信号通路促进上皮-间质转化和转移。
本研究构建了一种基于lncRNA的综合评分系统，用于临床预测GC患者的腹膜复发情况。
