A prognostic senescence-related long non-coding RNA signature identifies cold and hot tumors of stomach adenocarcinoma.

Patients with stomach adenocarcinoma (STAD) have a poor prognosis, and the efficacy of immunotherapy varies widely. The present study aimed to screen effective long non-coding RNAs (lncRNAs) as molecular targets for assessing the prognosis of STAD and guiding precision immunotherapy. A total of five key prognostic senescence-related lncRNAs (SenRLs; AL139147.1, LINC02057, AC093801.1, AL353804.2 and AC005363.2) were screened using bioinformatics methods. A novel validated prognostic risk model was constructed for STAD based on the SenRLs signature. For the training, test and entire set, the 5-year area under the curve values were 0.828, 0.703 and 0.772, respectively. A nomogram combining clinical variables and risk scores effectively predicted overall survival (OS) in patients with STAD. Clinical tissue samples were collected from patients with STAD, and quantitative PCR (qPCR) was employed to assess the tissue expression of SenRLs. The qPCR results showed that the expression of LINC02057, AL139147.1 and AC093801.1 was significantly higher in STAD tissues than in paracancerous tissues. By contrast, the expression of AC005363.2 and AL353804.2 was decreased in STAD tissues. The tissue expression profiles of these lncRNAs were consistent with the bioinformatics findings. The risk groups differed in their immune infiltrating cells, immune checkpoints and susceptibility to chemotherapeutic agents. Following clustering analysis, the two clusters had distinct tumor microenvironment profiles. Notably, based on well-established immunological characteristics, Cluster 2 was identified as representing hot tumors that are presumably more likely to benefit from immunotherapy. The newly developed SenRLs signature can serve as an independent prognostic biological marker of STAD. These SenRLs can effectively distinguish between hot and cold tumors, thereby better facilitating the screening of the beneficiary population for STAD immunotherapy.