长链非编码rna在胃癌腹膜复发中的转录格局和预测潜力

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2024-12-30 DOI:10.1186/s12943-024-02196-4

Xiao-Xia Cai, Guo-Ming Chen, Zi-Qi Zheng, Yi-Xin Yin, Shuang Wang, Li Qiao, Xiao-Jiang Chen, Bai-Wei Zhao, Jin-Ling Duan, Cheng-Cai Liang, Ruo-Peng Zhang, Cheng-Zhi Wei, Fei-Yang Zhang, Bo-Wen Huang, Ze-Xian Liu, Zhi-Wei Zhou, Dan Xie, Mu-Yan Cai, Shu-Qiang Yuan, Yuan-Fang Li, Run-Cong Nie

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引用次数: 0

摘要

长链非编码rna （lncRNAs）在胃癌（GC）的进展和转移中起着关键作用。然而，全面探索组织源性lncrna预测胃癌患者腹膜复发的研究仍然有限。本研究旨在研究lncrna在胃癌伴腹膜转移（PM）中的转录格局，并建立基于lncrna的综合评分来预测胃癌根治术后腹膜复发。我们分析了来自中山大学癌症中心（SYSUCC）发现队列的12例胃癌患者的配对腹膜、原发性胃肿瘤和正常组织标本中的lncrna转录组谱。通过与TCGA数据库和SYSUCC验证队列的交互分析确定了关键的lncrna。采用LASSO回归模型和nomogram COX回归构建评分模型，采用受试者工作特征曲线进行评分。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物致瘤性实验来检测lncRNAs在GC PM中的作用。筛选5种必要的lncrna并将其纳入PM风险评分，以预测腹膜无复发生存（pRFS）。我们制定了一个综合的nomogram评分，包括PM风险评分、pT、pN和肿瘤大小，该评分可以有效预测5年的pRFS，曲线下面积为0.79 （95% CI: 0.71-0.88）。随后，我们证明了其中一种lncrna cas15在体外促进GC细胞的侵袭和迁移，并促进GC细胞在体内的PM，初步验证了lncrna有助于GC的PM。机制分析表明，CASC15通过激活JNK和p38通路促进EMT和转移。本研究构建了基于lncrna的综合评分，用于临床预测患者腹膜复发。

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Transcriptional landscape and predictive potential of long noncoding RNAs in peritoneal recurrence of gastric cancer

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.

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

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