LncRNA expression signature identified using genome-wide transcriptomic profiling to predict lymph node metastasis in patients with stage T1 and T2 gastric cancer

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2023-11, Vol.26 (6), p.947-957
• Main Authors: Dong, Zhe-bin, Xiang, Han-ting, Wu, Heng-miao, Cai, Xian-lei, Chen, Zheng-wei, Chen, Sang-sang, He, Yi-Chen, Li, Hong, Yu, Wei-ming, Liang, Chao
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer Research; Computed tomography; Decision making; Deep learning; Gastric cancer; Gastroenterology; Genomes; Humans; Lymph nodes; Lymph Nodes - pathology; Lymphatic Metastasis - pathology; Lymphatic system; Medicine; Medicine & Public Health; Metastases; Metastasis; Non-coding RNA; Oncology; Original Article; Patients; Prediction models; RNA, Long Noncoding - genetics; Stomach Neoplasms - pathology; Surgical Oncology; Transcriptome; Transcriptomics; Tumor markers; Tumors
• ISSN: 1436-3291; 1436-3305; 1436-3305
• DOI: 10.1007/s10120-023-01428-8

Background Lymph node (LN) status is vital to evaluate the curative potential of relatively early gastric cancer (GC; T1–T2) treatment (endoscopic or surgery). Currently, there is a lack of robust and convenient methods to identify LN metastasis before therapeutic decision-making. Methods Genome-wide expression profiles of long noncoding RNA (lncRNA) in primary T1 gastric cancer data from The Cancer Genome Atlas (TCGA) was used to identify lncRNA expression signature capable of detecting LN metastasis of GC and establish a 10-lncRNA risk-prediction model based on deep learning. The performance of the lncRNA panel in diagnosing LN metastasis was evaluated both in silico and clinical validation methods. In silico validation was conducted using TCGA and Asian Cancer Research Group (ACRG) datasets. Clinical validation was performed on T1 and T2 patients, and the panel’s efficacy was compared with that of traditional tumor markers and computed tomography (CT) scans. Results Profiling of genome-wide RNA expression identified a panel of lncRNA to predict LN metastasis in T1 stage gastric cancer (AUC = 0.961). A 10-lncRNA risk-prediction model was then constructed, which was validated successfully in T1 and T2 datasets (TCGA, AUC = 0.852; ACRG, AUC = 0.834). Thereafter, the clinical performance of the lncRNA panel was validated in clinical cohorts (T1, AUC = 0.812; T2, AUC = 0.805; T1 + T2, AUC = 0.764). Notably, the panel demonstrated significantly better performance compared with CT and traditional tumor markers. Conclusions The novel 10-lncRNA could diagnose LN metastasis robustly in relatively early gastric cancer (T1–T2), with promising clinical potential.