Mitochondrial Autophagy-related LncRNAs As Prognostic Biomarkers and Therapeutic Targets in Gastric Adenocarcinoma

Overview

Journal Discov Oncol

Publisher Springer

Specialty Oncology

Date 2025 Mar 8

PMID 40056287

Authors

Rongbo Han

Jinxin Wei

Benxin Zhao

Rongchang Zhao

Affiliations

Soon will be listed here.

Abstract

Understanding the tumor microenvironment (TME) and the role of long noncoding RNAs (lncRNAs) in gastric adenocarcinoma (GA) is crucial, as these elements not only influence tumor progression but also provide opportunities for more precise prognostic assessments and tailored therapeutic interventions. This study identified mitochondrial autophagy-related lncRNAs, constructed a robust prognostic risk model, and explored the relationship between immune microenvironment characteristics and therapeutic responses. The model's performance was evaluated using ROC curves, Kaplan-Meier survival analysis, and nomograms. Our results demonstrate that the model outperforms traditional clinical factors, such as age and stage, in predicting patient outcomes. Immune cell analysis revealed distinct correlations with risk scores, and several immune checkpoint genes exhibited differential expression between risk groups. Drug sensitivity analysis suggested that low-risk patients could benefit more from ICIs, Oxaliplatin, Irinotecan, Afatinib, and Dabrafenib, while high-risk patients showed higher sensitivity to IGF1R3801, JQI, WZ4003 and NU7441. The identified lncRNA-based risk model provides a reliable prognostic tool for GA patients and highlights distinct immune microenvironment profiles that may influence treatment responses. These findings contribute to developing personalized therapeutic strategies targeting lncRNAs and the TME in GA.

References

Rousseau A, Parisi C, Barlesi F . Anti-TIGIT therapies for solid tumors: a systematic review. ESMO Open. 2023; 8(2):101184. PMC: 10030909. DOI: 10.1016/j.esmoop.2023.101184. View

Ma J, Hu S, Hsieh M, Lee Y, Huang S, Chen K . PEAL Score to Predict the Mortality Risk of Cardiogenic Shock in the Emergency Department: An Observational Study. J Pers Med. 2023; 13(11). PMC: 10672116. DOI: 10.3390/jpm13111614. View

Zhou H, Zhu P, Wang J, Zhu H, Ren J, Chen Y . Pathogenesis of cardiac ischemia reperfusion injury is associated with CK2α-disturbed mitochondrial homeostasis via suppression of FUNDC1-related mitophagy. Cell Death Differ. 2018; 25(6):1080-1093. PMC: 5988750. DOI: 10.1038/s41418-018-0086-7. View

Vidovic D, Huynh T, Konda P, Dean C, Cruickshank B, Sultan M . ALDH1A3-regulated long non-coding RNA NRAD1 is a potential novel target for triple-negative breast tumors and cancer stem cells. Cell Death Differ. 2019; 27(1):363-378. PMC: 7206030. DOI: 10.1038/s41418-019-0362-1. View

Yao J, Wang J, Xu Y, Guo Q, Sun Y, Liu J . CDK9 inhibition blocks the initiation of PINK1-PRKN-mediated mitophagy by regulating the SIRT1-FOXO3-BNIP3 axis and enhances the therapeutic effects involving mitochondrial dysfunction in hepatocellular carcinoma. Autophagy. 2021; 18(8):1879-1897. PMC: 9450969. DOI: 10.1080/15548627.2021.2007027. View

Esposito R, Bosch N, Lanzos A, Polidori T, Pulido-Quetglas C, Johnson R . Hacking the Cancer Genome: Profiling Therapeutically Actionable Long Non-coding RNAs Using CRISPR-Cas9 Screening. Cancer Cell. 2019; 35(4):545-557. DOI: 10.1016/j.ccell.2019.01.019. View

Zhou Y, Wei X, Li W, Zhang S, Zhao Y . Comprehensive analysis of mitophagy-related subtypes of breast cancer and the association with immune related characteristics. Heliyon. 2023; 9(12):e23267. PMC: 10746530. DOI: 10.1016/j.heliyon.2023.e23267. View

Huang Y, Ouyang W, Wang Z, Huang H, Ou Q, Lin R . A Comprehensive Analysis of Programmed Cell Death-Associated Genes for Tumor Microenvironment Evaluation Promotes Precise Immunotherapy in Patients with Lung Adenocarcinoma. J Pers Med. 2023; 13(3). PMC: 10058589. DOI: 10.3390/jpm13030476. View

Nair L, Chung H, Basu U . Regulation of long non-coding RNAs and genome dynamics by the RNA surveillance machinery. Nat Rev Mol Cell Biol. 2020; 21(3):123-136. PMC: 7107043. DOI: 10.1038/s41580-019-0209-0. View

Hoshi H . Management of Gastric Adenocarcinoma for General Surgeons. Surg Clin North Am. 2020; 100(3):523-534. DOI: 10.1016/j.suc.2020.02.004. View

10.

Esteban-Martinez L, Sierra-Filardi E, McGreal R, Salazar-Roa M, Marino G, Seco E . Programmed mitophagy is essential for the glycolytic switch during cell differentiation. EMBO J. 2017; 36(12):1688-1706. PMC: 5470043. DOI: 10.15252/embj.201695916. View

11.

Tong X, Yang X, Tong X, Zhai D, Liu Y . Complement system-related genes in stomach adenocarcinoma: Prognostic signature, immune landscape, and drug resistance. Front Genet. 2022; 13:903421. PMC: 9493128. DOI: 10.3389/fgene.2022.903421. View

12.

Wang Z, Yang B, Zhang M, Guo W, Wu Z, Wang Y . lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer. Cancer Cell. 2018; 33(4):706-720.e9. PMC: 6143179. DOI: 10.1016/j.ccell.2018.03.006. View

13.

Luo L, Zhang W, Li Z . LncRNA HAGLR May Aggravate Melanoma Malignancy Via miR-4644/ASB11 Pathway. Mol Biotechnol. 2023; 65(10):1619-1631. DOI: 10.1007/s12033-023-00672-8. View

14.

Koustas E, Trifylli E, Sarantis P, Kontolatis N, Damaskos C, Garmpis N . The Implication of Autophagy in Gastric Cancer Progression. Life (Basel). 2021; 11(12). PMC: 8705750. DOI: 10.3390/life11121304. View

15.

Lin Y, Li J, Liang S, Chen Y, Li Y, Cun Y . Pan-cancer Analysis Reveals m6A Variation and Cell-specific Regulatory Network in Different Cancer Types. Genomics Proteomics Bioinformatics. 2024; 22(4). PMC: 11514823. DOI: 10.1093/gpbjnl/qzae052. View

16.

Li Y, Zhang J, Huo C, Ding N, Li J, Xiao J . Dynamic Organization of lncRNA and Circular RNA Regulators Collectively Controlled Cardiac Differentiation in Humans. EBioMedicine. 2017; 24:137-146. PMC: 5652025. DOI: 10.1016/j.ebiom.2017.09.015. View

17.

Fujii S, Mitsunaga S, Yamazaki M, Hasebe T, Ishii G, Kojima M . Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome. Cancer Sci. 2008; 99(9):1813-9. PMC: 11159933. DOI: 10.1111/j.1349-7006.2008.00893.x. View

18.

Kim J, Piao H, Kim B, Yao F, Han Z, Wang Y . Long noncoding RNA MALAT1 suppresses breast cancer metastasis. Nat Genet. 2018; 50(12):1705-1715. PMC: 6265076. DOI: 10.1038/s41588-018-0252-3. View

19.

Zhang M, Hu S, Min M, Ni Y, Lu Z, Sun X . Dissecting transcriptional heterogeneity in primary gastric adenocarcinoma by single cell RNA sequencing. Gut. 2020; 70(3):464-475. PMC: 7873416. DOI: 10.1136/gutjnl-2019-320368. View