2. Academic Validation
  3. Transcriptional landscape and predictive potential of long noncoding RNAs in peritoneal recurrence of gastric cancer

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

  • Mol Cancer. 2024 Dec 30;23(1):284. doi: 10.1186/s12943-024-02196-4.
Xiao-Xia Cai # 1,  Guo-Ming Chen # 2,  Zi-Qi Zheng # 2,  Yi-Xin Yin # 1,  Shuang Wang # 3,  Li Qiao # 4,  Xiao-Jiang Chen 2,  Bai-Wei Zhao 2,  Jin-Ling Duan 3,  Cheng-Cai Liang 2,  Ruo-Peng Zhang 2,  Cheng-Zhi Wei 2,  Fei-Yang Zhang 2,  Bo-Wen Huang 2,  Ze-Xian Liu 1,  Zhi-Wei Zhou 2,  Dan Xie 1,  Mu-Yan Cai 5,  Shu-Qiang Yuan 6,  Yuan-Fang Li 7,  Run-Cong Nie 8
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Department of Pathology, 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.
  • 4 Department of Rehabilitation Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510060, P. R. China.
  • 5 Department of Pathology, 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. caimy@sysucc.org.cn.
  • 6 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. yuanshq@sysucc.org.cn.
  • 7 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. liyuanf@sysucc.org.cn.
  • 8 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. nierc@sysucc.org.cn.
  • # Contributed equally.
PMID: 39736670 DOI: 10.1186/s12943-024-02196-4
Abstract

Background: 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.

Methods: 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.

Result: 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.

Conclusion: A lncRNA-based integrated score was constructed in this study to predict peritoneal recurrence in patients clinically.

Keywords

Gastric cancer; Long noncoding RNA; Peritoneal recurrence; Transcriptome profiles.

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