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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Integrated analysis from multicentre studies identities m7G-related lncRNA-derived molecular subtypes and risk
Mingwei Ma1, Jie Li1, Ziyang Zeng1
1Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Introduction:
Gastric 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.
Methods:
This 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.
Results:
After 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.
Discussion:
In 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.
Insights
This study reveals m7G-related lncRNAs impact gastric cancer immunity and prognosis. A novel risk model identifies patients who may benefit from immunotherapy and predicts outcomes.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Gastric cancer (GC) is a leading cause of cancer death globally.
- Effective chemotherapy for advanced GC is limited, making immunotherapy a promising avenue.
- Identifying patient subgroups that benefit from immunotherapy is crucial for improving treatment efficacy.
Purpose of the Study:
- To investigate the role of m7G-related long non-coding RNAs (lncRNAs) in the gastric cancer tumor immune microenvironment.
- To identify molecular subtypes of GC based on m7G-related lncRNAs.
- To develop a risk prediction model for immunotherapy response and prognosis in GC patients.
Main Methods:
- Analysis of 29 immune cell types and immune functions in GC patients.
- Identification of m7G-related lncRNAs and their molecular subtypes.
- Development of a risk score and nomogram based on five key lncRNAs (LINC00924, LINC00944, LINC00865, LINC00702, ZFAS1).
- Experimental validation using RT-qPCR.
Main Results:
- Three molecular subtypes of m7G-related lncRNAs were identified, with subtype B showing higher immune infiltration and potential benefit from immunotherapy.
- Two distinct regulator subtypes with significant immunological differences were defined, aiding in predicting response to immune checkpoint inhibitor (ICI) treatment.
- A risk score model was established, linking high-risk scores to poor prognosis and better response to certain chemotherapies, suggesting potential benefit from immunotherapy.
Conclusions:
- m7G-related lncRNAs significantly influence the tumor immune microenvironment in gastric cancer.
- The developed risk prediction model can identify GC patients likely to benefit from immunotherapy.
- This research provides a novel approach for predicting prognosis and guiding treatment strategies in gastric cancer.
