Comprehensive Analysis Revealed P4Hs As New Biomarkers for Prognosis and Immunotherapy in Head and Neck Cancer

Overview

Journal Sci Rep

Specialty Science

Date 2024 May 28

PMID 38806556

Authors

Huan Zhou

Yulin Lei

Jing Luo

Jianmei Wang

Lin Peng

Kelin Mou

Li Xiang

Yuhao Luo

Affiliations

Soon will be listed here.

Abstract

Prolyl 4-hydroxylases (P4Hs) are a family of key modifying enzymes in collagen synthesis. P4Hs have been confirmed to be closely associated with tumor occurrence and development. However, the expression of P4Hs in head and neck cancer (HNSC) as well as its relationship with prognosis and tumor immunity infiltration has not yet been analyzed. We investigated the transcriptional expression, survival data, and immune infiltration of P4Hs in patients with HNSC from multiple databases. P4H1-3 expression was significantly higher in HNSC tumor tissues than in normal tissues. Moreover, P4HA1 and P4HA2 were associated with tumor stage, patient prognosis, and immune cell infiltration. P4HA3 was related to patient prognosis and immune cell infiltration. Correlation experiments confirmed that P4HA1 may serve as a prognosis biomarker and plays a role in the progression of nasopharyngeal carcinoma. These findings suggest that P4HA1-3 may be a novel biomarker for the prognosis and treatment of HNSC, which is expected to support the development of new therapies for patients with head and neck tumors and improve patient outcomes.

References

Wu J, Zhu H, Gao F, Wang R, Hu K . Circulating Tumor Cells: A Promising Biomarker in the Management of Nasopharyngeal Carcinoma. Front Oncol. 2021; 11:724150. PMC: 8588829. DOI: 10.3389/fonc.2021.724150. View

Sun W, Kosyna F, Jelkmann W, Depping R . Prolyl-4-Hydroxylase 2 Potentially Contributes to Hepatocellular Carcinoma-Associated Erythrocytosis by Maintaining Hepatocyte Nuclear Factor-4α Expression. Cell Physiol Biochem. 2015; 37(6):2257-64. DOI: 10.1159/000438581. View

Vasta J, Raines R . Collagen Prolyl 4-Hydroxylase as a Therapeutic Target. J Med Chem. 2018; 61(23):10403-10411. PMC: 6344319. DOI: 10.1021/acs.jmedchem.8b00822. View

Shang L, Jiang W, Zhang J, Wu W . [P4HA2 promotes occurrence and progression of liver cancer by regulating the PI3K/Akt/mTOR signaling pathway]. Nan Fang Yi Ke Da Xue Xue Bao. 2022; 42(5):665-672. PMC: 9178641. DOI: 10.12122/j.issn.1673-4254.2022.05.06. View

Grimmer C, Balbus N, Lang U, Aigner T, Cramer T, Muller L . Regulation of type II collagen synthesis during osteoarthritis by prolyl-4-hydroxylases: possible influence of low oxygen levels. Am J Pathol. 2006; 169(2):491-502. PMC: 1698781. DOI: 10.2353/ajpath.2006.050738. View

Budach W, Hehr T, Budach V, Belka C, Dietz K . A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck. BMC Cancer. 2006; 6:28. PMC: 1379652. DOI: 10.1186/1471-2407-6-28. View

Atkinson A, Renziehausen A, Wang H, Lo Nigro C, Lattanzio L, Merlano M . Collagen Prolyl Hydroxylases Are Bifunctional Growth Regulators in Melanoma. J Invest Dermatol. 2018; 139(5):1118-1126. PMC: 7015666. DOI: 10.1016/j.jid.2018.10.038. View

Lin J, Jiang L, Wang X, Wei W, Song C, Cui Y . P4HA2 Promotes Epithelial-to-Mesenchymal Transition and Glioma Malignancy through the Collagen-Dependent PI3K/AKT Pathway. J Oncol. 2021; 2021:1406853. PMC: 8382519. DOI: 10.1155/2021/1406853. 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

10.

Gou W, Yang Y, Shan Q, Xia S, Ma Y . P4HA1, transcriptionally activated by STAT1, promotes esophageal cancer progression. Pathol Int. 2023; 73(4):147-158. DOI: 10.1111/pin.13310. View

11.

Pulte D, Brenner H . Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist. 2010; 15(9):994-1001. PMC: 3228039. DOI: 10.1634/theoncologist.2009-0289. View

12.

Ramshaw J, Shah N, Brodsky B . Gly-X-Y tripeptide frequencies in collagen: a context for host-guest triple-helical peptides. J Struct Biol. 1998; 122(1-2):86-91. DOI: 10.1006/jsbi.1998.3977. View

13.

Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Jemal A . Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87-108. DOI: 10.3322/caac.21262. View

14.

Kanehisa M, Goto S . KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 1999; 28(1):27-30. PMC: 102409. DOI: 10.1093/nar/28.1.27. View

15.

Shang C, Feng L, Gu Y, Hong H, Hong L, Hou J . Impact of Multidisciplinary Team Management on the Survival Rate of Head and Neck Cancer Patients: A Cohort Study Meta-analysis. Front Oncol. 2021; 11:630906. PMC: 7982739. DOI: 10.3389/fonc.2021.630906. View

16.

Mo L, Su Y, Yuan J, Xiao Z, Zhang Z, Lan X . Comparisons of Forecasting for Survival Outcome for Head and Neck Squamous Cell Carcinoma by using Machine Learning Models based on Multi-omics. Curr Genomics. 2023; 23(2):94-108. PMC: 9878835. DOI: 10.2174/1389202923666220204153744. View

17.

Myllyharju J . Prolyl 4-hydroxylases, the key enzymes of collagen biosynthesis. Matrix Biol. 2003; 22(1):15-24. DOI: 10.1016/s0945-053x(03)00006-4. View

18.

Chow L . Head and Neck Cancer. N Engl J Med. 2020; 382(1):60-72. DOI: 10.1056/NEJMra1715715. View

19.

Ge W, Yue M, Lin R, Zhou T, Xu H, Wang Y . PLA2G2A cancer-associated fibroblasts mediate pancreatic cancer immune escape via impeding antitumor immune response of CD8 cytotoxic T cells. Cancer Lett. 2023; 558:216095. DOI: 10.1016/j.canlet.2023.216095. View

20.

Robinson A, Chakravarthi B, Agarwal S, Chandrashekar D, Davenport M, Chen G . Collagen modifying enzyme P4HA1 is overexpressed and plays a role in lung adenocarcinoma. Transl Oncol. 2021; 14(8):101128. PMC: 8170159. DOI: 10.1016/j.tranon.2021.101128. View