Exploring the Prognostic and Therapeutic Value of HIF1A in Lung Adenocarcinoma

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Sep 25

PMID 39318795

Authors

Zhimin Lu

Yanyu Bi

Jialu Jiang

Xuming Yao

Guoxin Hou

Affiliations

Soon will be listed here.

Abstract

Lung adenocarcinoma (LUAD) remains a challenge within the realm of non-small cell lung cancer (NSCLC), demanding innovative diagnostic and therapeutic solutions. In this study, we systematically detected the correlation between the expression of hypoxia-induced factor 1A (HIF1A) and the clinical characteristics of LUAD, alongside lung squamous cell carcinoma (LUSC). Our bioinformatic analysis reveals that HIF1A mRNA expression is significantly upregulated in both LUAD and LUSC samples compared to non-tumorous lung tissues. The overexpression is positively correlated with increased copy number variation and negatively associated with promoter methylation. However, meta-analysis and survival analyses revealed a pronounced association between elevated HIF1A expression and poor clinical outcome specifically within the LUAD subset, with no such correlation evident in LUSC. Additionally, we explored the interplay between HIF1A expression, leukocyte infiltration, and the presence of immunosuppressive markers, revealing HIF1A's suppressive role in cytotoxicity against cancer cells. Furthermore, we performed in silico prediction to explore the correlations between HIF1A and its interacting proteins, associated pathways, glycolysis, and mA modification, and the feasibility of targeting HIF1A with specific drugs. In summary, our study revealed the prognostic significance and therapeutic potential of HIF1A in LUAD.

References

Zhao M, Zhang Y, Zhang H, Wang S, Zhang M, Chen X . Hypoxia-induced cell stemness leads to drug resistance and poor prognosis in lung adenocarcinoma. Lung Cancer. 2014; 87(2):98-106. DOI: 10.1016/j.lungcan.2014.11.017. View

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

Cowman S, Koh M . Revisiting the HIF switch in the tumor and its immune microenvironment. Trends Cancer. 2021; 8(1):28-42. PMC: 8702465. DOI: 10.1016/j.trecan.2021.10.004. View

Amelio I, Mancini M, Petrova V, Cairns R, Vikhreva P, Nicolai S . p53 mutants cooperate with HIF-1 in transcriptional regulation of extracellular matrix components to promote tumor progression. Proc Natl Acad Sci U S A. 2018; 115(46):E10869-E10878. PMC: 6243248. DOI: 10.1073/pnas.1808314115. View

Cerami E, Gao J, Dogrusoz U, Gross B, Sumer S, Aksoy B . The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012; 2(5):401-4. PMC: 3956037. DOI: 10.1158/2159-8290.CD-12-0095. View

Anusewicz D, Orzechowska M, Bednarek A . Lung squamous cell carcinoma and lung adenocarcinoma differential gene expression regulation through pathways of Notch, Hedgehog, Wnt, and ErbB signalling. Sci Rep. 2020; 10(1):21128. PMC: 7713208. DOI: 10.1038/s41598-020-77284-8. View

Hou G, Lu Z, Yang Z, Jiang J . Prognostic value of metabolic genes in lung adenocarcinoma via integrative analyses. Genomics. 2022; 114(4):110425. DOI: 10.1016/j.ygeno.2022.110425. View

Wang C, Yu Q, Song T, Wang Z, Song L, Yang Y . The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing. Signal Transduct Target Ther. 2022; 7(1):289. PMC: 9411197. DOI: 10.1038/s41392-022-01130-8. View

Lau S, Pan Y, Velcheti V, Wong K . Squamous cell lung cancer: Current landscape and future therapeutic options. Cancer Cell. 2022; 40(11):1279-1293. DOI: 10.1016/j.ccell.2022.09.018. View

10.

Bao M, Chak-Lui Wong C . Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer. Cells. 2021; 10(7). PMC: 8304710. DOI: 10.3390/cells10071715. View

11.

Ge Y, Xu K . Alpha-synuclein contributes to malignant progression of human meningioma via the Akt/mTOR pathway. Cancer Cell Int. 2016; 16:86. PMC: 5109801. DOI: 10.1186/s12935-016-0361-y. View

12.

Cai L, Lin S, Girard L, Zhou Y, Yang L, Ci B . LCE: an open web portal to explore gene expression and clinical associations in lung cancer. Oncogene. 2018; 38(14):2551-2564. PMC: 6477796. DOI: 10.1038/s41388-018-0588-2. View

13.

Chen J, Dhahbi J . Lung adenocarcinoma and lung squamous cell carcinoma cancer classification, biomarker identification, and gene expression analysis using overlapping feature selection methods. Sci Rep. 2021; 11(1):13323. PMC: 8233431. DOI: 10.1038/s41598-021-92725-8. View

14.

Travis W . Pathology of lung cancer. Clin Chest Med. 2011; 32(4):669-92. DOI: 10.1016/j.ccm.2011.08.005. View

15.

Siegel R, Miller K, Fuchs H, Jemal A . Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1):7-33. DOI: 10.3322/caac.21708. View

16.

. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014; 511(7511):543-50. PMC: 4231481. DOI: 10.1038/nature13385. View

17.

Zhang H, Wang S, Wang L, Lin H, Zhu J, Chen R . m6A methyltransferase METTL3-induced lncRNA SNHG17 promotes lung adenocarcinoma gefitinib resistance by epigenetically repressing LATS2 expression. Cell Death Dis. 2022; 13(7):657. PMC: 9334586. DOI: 10.1038/s41419-022-05050-x. View

18.

Zhang W, Zhang Q, Zhang M, Zhang Y, Li F, Lei P . Network analysis in the identification of special mechanisms between small cell lung cancer and non-small cell lung cancer. Thorac Cancer. 2016; 5(6):556-64. PMC: 4704339. DOI: 10.1111/1759-7714.12134. View

19.

Ji J, Wang Y, Jing A, Ma L, Yang J, Ren D . HIF1A-dependent overexpression of MTFP1 promotes lung squamous cell carcinoma development by activating the glycolysis pathway. Heliyon. 2024; 10(7):e28440. PMC: 11059513. DOI: 10.1016/j.heliyon.2024.e28440. View

20.

Xu F, Huang X, Li Y, Chen Y, Lin L . mA-related lncRNAs are potential biomarkers for predicting prognoses and immune responses in patients with LUAD. Mol Ther Nucleic Acids. 2021; 24:780-791. PMC: 8094594. DOI: 10.1016/j.omtn.2021.04.003. View