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Molecular characterization of metabolic subtypes of gastric cancer based on metabolism-related lncRNA

ABSTRACT: Increasing evidence has demonstrated that lncRNAs are critical regulators in diverse biological processes, but the function of lncRNA in metabolic regulation remains largely unexplored. In this study, we evaluated the association between lncRNA and metabolic pathways and identified metabolism-related lncRNAs. Gastric cancer can be mainly subdivided into 2 clusters based on these metabolism-related lncRNA regulators. Comparative analysis shows that these subtypes are found to be highly consistent with previously identified subtypes based on other omics data. Functional enrichment analysis shows that they are enriched in distinct biological processes. Mutation analysis shows that ABCA13 is a protective factor in subtype C1 but a risk factor in C2. Analysis of chemotherapeutic and immunotherapeutic sensitivity shows that these subtypes tend to display distinct sensitivity to the same chemical drugs. In conclusion, these findings demonstrated the significance of lncRNA in metabolic regulation. These metabolism-related lncRNA regulators can improve our understanding of the underlying mechanism of lncRNAs and advance the research of immunotherapies in the clinical management of gastric cancer.

SUBMITTER: Li L

PROVIDER: S-EPMC8563741 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionGastric cancer (GC) is the fourth leading cause of cancer death worldwide. Due to the lack of effective chemotherapy methods for advanced gastric cancer and poor prognosis, the emergence of immunotherapy has brought new hope to gastric cancer. Further research is needed to improve the response rate to immunotherapy and identify the populations with potential benefits of immunotherapy. It is unclear whether m7G-related lncRNAs influence tumour immunity and the prognosis of immunotherapy.MethodsThis study evaluated 29 types of immune cells and immune functions in gastric cancer patients, and m7G-related lncRNAs and their molecular subtypes were identified. In addition, we also studied the biological function characteristics of m7G-related lncRNA molecular subtypes. Finally, the patient's risk score was calculated based on m7G-related lncRNAs, and a nomogram of staging and risk groups was established to predict the prognosis. For experimental verification, RT-qPCR were preformed from the native cohort.ResultsAfter identifying m7G-related lncRNAs and their molecular subtypes, we found three molecular subtypes, the B subtype had the highest level of infiltration, and the B subtype may benefit more from immunotherapy. We divided GC patients into two regulator subtypes based on biological function. The two subtypes have significant immunological differences and can be used to judge ICI treatment. We established a risk score formula based on five lncRNAs, including LINC00924, LINC00944, LINC00865, LINC00702, and ZFAS1. Patients with poor prognoses were closely related to patients in the high-risk group. After comprehensive analysis of different risk groups, the efficacy of the high-risk group on bleomycin, cisplatin, docetaxel, doxorubicin and etoposide was better than that of the low-risk group, suggesting that risk subgroups based on risk scores play a guiding role in chemotherapy and that the high-risk group may benefit more from immunotherapy. RT-qPCR results showed that LINC00924, LINC00944, and LINC00865 were highly expressed in tumour tissues, while LINC00702 and ZFAS1 were expressed at low levels in tumour tissues.DiscussionIn conclusion, we were the first to discover that m7G-related lncRNAs play a vital role in the tumour immune microenvironment of gastric cancer, and a risk prediction model was established to identify patients with potential benefits from immunotherapy and predict the prognosis of GC patients.

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Molecular characterization of metabolic subtypes of gastric cancer based on metabolism-related lncRNA

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