Derivation of a Novel CIHI in Patients with Lung Adenocarcinoma for Estimating Tumor Microenvironment and Clinical Prognosis

Overview

Journal Dis Markers

Publisher Wiley

Specialty Biochemistry

Date 2021 Dec 2

PMID 34853621

Citations 2

Authors

Liang Zhou

Guangyan Xu

Li Wang

Jianyong Zhang

Weimin Li

Affiliations

Soon will be listed here.

Abstract

An interaction between hypoxia and immunity has been confirmed in tumor tissue. However, there is no combined biomarker for diagnosis on this basis. Therefore, we developed a scoring formula based on markers of hypoxia and immunity. Firstly, the hypoxia-immune formula of lung adenocarcinoma (LUAD) was derived using LASSO-Cox regression in three cohorts from public database, and the corresponding score was calculated for each patient. The formula is as follows: combined hypoxia and immune index (CIHI) = LDHA expression × 0.2252 + GAPDH expression × 0.0727 + ANGPTL4 expression × 0.0724 + VEGFC expression × 0.1911 + DKK1 expression × 0.1355 + ADM expression × 0.0588 + BTK expression × -0.1659. Meanwhile, patients were divided into groups according to high and low CIHI, and expression profiles of hypoxia markers and immune markers were analyzed in different groups. CIHI was used to confirm that patients with high CIHI represented a state of hypoxia-immunity, which had worse overall survival. We also discussed the evaluation value in the immune microenvironment and clinical application of CIHI. In conclusion, this study developed and validated a hypoxia-immune formula that can guide hypoxia modifier treatment and immunotherapy in LUAD.

Citing Articles

Single-Cell RNA Sequencing Analysis of Gene Regulatory Network Changes in the Development of Lung Adenocarcinoma.

Yu D, Zhang S, Liu Z, Xu L, Chen L, Xie L Biomolecules. 2023; 13(4).

PMID: 37189418 PMC: 10135828. DOI: 10.3390/biom13040671.

Li M, Zhang L, Feng M, Huang X J Immunol Res. 2022; 2022:3258400.

PMID: 35991123 PMC: 9385364. DOI: 10.1155/2022/3258400.

References

Liu Y, Pang Z, Zhao X, Zeng Y, Shen H, Du J . Prognostic model of AU-rich genes predicting the prognosis of lung adenocarcinoma. PeerJ. 2021; 9:e12275. PMC: 8504460. DOI: 10.7717/peerj.12275. View

Chang L, Fang S, Gu W . The Molecular Mechanism of Metabolic Remodeling in Lung Cancer. J Cancer. 2020; 11(6):1403-1411. PMC: 6995370. DOI: 10.7150/jca.31406. View

Vanhove K, Graulus G, Mesotten L, Thomeer M, Derveaux E, Noben J . The Metabolic Landscape of Lung Cancer: New Insights in a Disturbed Glucose Metabolism. Front Oncol. 2019; 9:1215. PMC: 6873590. DOI: 10.3389/fonc.2019.01215. View

Sun J, Zhao T, Zhao D, Qi X, Bao X, Shi R . Development and validation of a hypoxia-related gene signature to predict overall survival in early-stage lung adenocarcinoma patients. Ther Adv Med Oncol. 2020; 12:1758835920937904. PMC: 7333486. DOI: 10.1177/1758835920937904. View

Shang Q, Dong Z, Liu C, Bai Y, Guo C, Zhang L . Differential effects of agonistic 4-1BB (CD137) monoclonal antibody on the maturation and functions of hypoxic dendritic cells. Int Immunopharmacol. 2014; 23(2):609-16. DOI: 10.1016/j.intimp.2014.10.012. View

Liu L, He H, Peng Y, Yang Z, Gao S . A four-gene prognostic signature for predicting the overall survival of patients with lung adenocarcinoma. PeerJ. 2021; 9:e11911. PMC: 8465999. DOI: 10.7717/peerj.11911. View

Campbell S, Wellen K . Metabolic Signaling to the Nucleus in Cancer. Mol Cell. 2018; 71(3):398-408. DOI: 10.1016/j.molcel.2018.07.015. View

Ma B, Cheng H, Mu C, Geng G, Zhao T, Luo Q . The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression. Nat Commun. 2019; 10(1):1034. PMC: 6399320. DOI: 10.1038/s41467-019-08618-y. View

Wang D, Wang N, Li X, Chen X, Shen B, Zhu D . Tumor mutation burden as a biomarker in resected gastric cancer via its association with immune infiltration and hypoxia. Gastric Cancer. 2021; 24(4):823-834. DOI: 10.1007/s10120-021-01175-8. View

10.

Wang Y, Chen L, Yu M, Fang Y, Qian K, Wang G . Immune-related signature predicts the prognosis and immunotherapy benefit in bladder cancer. Cancer Med. 2020; 9(20):7729-7741. PMC: 7571842. DOI: 10.1002/cam4.3400. View

11.

Yoshihara K, Shahmoradgoli M, Martinez E, Vegesna R, Kim H, Torres-Garcia W . Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013; 4:2612. PMC: 3826632. DOI: 10.1038/ncomms3612. View

12.

Walsh S, Simovic B, Chen L, Bastin D, Nguyen A, Stephenson K . Endogenous T cells prevent tumor immune escape following adoptive T cell therapy. J Clin Invest. 2019; 129(12):5400-5410. PMC: 6877330. DOI: 10.1172/JCI126199. View

13.

Ancey P, Contat C, Meylan E . Glucose transporters in cancer - from tumor cells to the tumor microenvironment. FEBS J. 2018; 285(16):2926-2943. DOI: 10.1111/febs.14577. View

14.

Canadas I, Thummalapalli R, Kim J, Kitajima S, Jenkins R, Christensen C . Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nat Med. 2018; 24(8):1143-1150. PMC: 6082722. DOI: 10.1038/s41591-018-0116-5. View

15.

Chen F, Chen J, Yang L, Liu J, Zhang X, Zhang Y . Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells. Nat Cell Biol. 2019; 21(4):498-510. DOI: 10.1038/s41556-019-0299-0. View

16.

Ruiz de Galarreta M, Bresnahan E, Molina-Sanchez P, Lindblad K, Maier B, Sia D . β-Catenin Activation Promotes Immune Escape and Resistance to Anti-PD-1 Therapy in Hepatocellular Carcinoma. Cancer Discov. 2019; 9(8):1124-1141. PMC: 6677618. DOI: 10.1158/2159-8290.CD-19-0074. View

17.

Zhang H, Almuqbil R, Alhudaithi S, Sunbul F, da Rocha S . Pulmonary administration of a CSF-1R inhibitor alters the balance of tumor-associated macrophages and supports first-line chemotherapy in a lung cancer model. Int J Pharm. 2021; 598:120350. DOI: 10.1016/j.ijpharm.2021.120350. View

18.

Liikanen I, Lauhan C, Quon S, Omilusik K, Phan A, Bartroli L . Hypoxia-inducible factor activity promotes antitumor effector function and tissue residency by CD8+ T cells. J Clin Invest. 2021; 131(7). PMC: 8011896. DOI: 10.1172/JCI143729. View

19.

Wu X, Gu Z, Chen Y, Chen B, Chen W, Weng L . Application of PD-1 Blockade in Cancer Immunotherapy. Comput Struct Biotechnol J. 2019; 17:661-674. PMC: 6558092. DOI: 10.1016/j.csbj.2019.03.006. View

20.

Li J, Eu J, Kong L, Wang L, Lim Y, Goh B . Targeting Metabolism in Cancer Cells and the Tumour Microenvironment for Cancer Therapy. Molecules. 2020; 25(20). PMC: 7588013. DOI: 10.3390/molecules25204831. View