Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 28;14(1):12234.
doi: 10.1038/s41598-024-62678-9.

Comprehensive analysis revealed P4Hs as new biomarkers for prognosis and immunotherapy in head and neck cancer

Huan Zhou #  1 , Yulin Lei #  1 , Jing Luo #  2 , Jianmei Wang  3 , Lin Peng  4 , Kelin Mou  1 , Li Xiang  5 , Yuhao Luo  6   7
Affiliations

Comprehensive analysis revealed P4Hs as new biomarkers for prognosis and immunotherapy in head and neck cancer

Huan Zhou et al. Sci Rep. .

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.

Keywords: Bioinformation analysis; HNSC; Immune infiltration; P4HA1-3; Prognostic biomarkers.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Expression level of P4Hs in tumor and normal tissues. The Xiantao Academy tool was used to analyze P4HA mRNA expression in pancarcinoma tissues and corresponding control tissues. Tumors and normal tissue are shown in red and blue, respectively.
Figure 2
Figure 2
High expression of P4Hs in HNSC. (A), (B) P4H expression was higher in HNSC than in normal tissues, as determined using the GEPIA2 profile and BOX plot analysis module.
Figure 3
Figure 3
Expression levels of P4Hs in different stages of HNSC4 were analyzed using the SangerBox tool.
Figure 4
Figure 4
The protein expressions of P4Hs in thyroid cancer and oral squamous cell carcinoma were analyzed by The Human Protein Atlas. (A) Expression of P4Hs in normal thyroid tissue and thyroid cancer. (B) Expression of P4Hs in normal oral mucosa and oral squamous cell carcinoma.
Figure 5
Figure 5
The Prognostic Value of mRNA Level of P4Hs in HNSC Patients. (A) Kaplan–Meier curves are plotted to predict the OS and PFS of HNSC patients. (B) The Kaplan–Meier curves plotted the risk tree of P4Hs expression for poor prognosis in HNSC patients.
Figure 6
Figure 6
P4Hs Gene Expression and Mutation Analysis in HNSC. (A)The expression and mutation of P4Hs gene in HNSC were analyzed by cBioportal. (B) Correlation between P4Hs genes was analyzed using cBioportal.
Figure 7
Figure 7
P4Hs significantly related genes and P4Hs function. (A) P4Hs and the network of 20 most similar genes were analyzed by Genemania. (B) GO and KEGG enrichment of P4Hs and similar genes were analyzed using the Xiantao Academy tool. (C) KEGG functional enrichment analysis of P4Hs and associated genes was performed by the SangerBox tool.
Figure 8
Figure 8
The expression of P4Hs in HNSCS is correlated with the level of immune infiltration and the expression of immune checkpoints (A The Xiantao Academy tool; B Tumor Immune Estimation Resource; C The Sangerbox tool).
Figure 9
Figure 9
P4HA1 is highly expressed in nasopharyngeal carcinoma tissues and promotes the proliferation and metastasis of nasopharyngeal carcinoma. (A) P4HA1 is highly expressed in nasopharyngeal carcinoma. (B) Kaplan–Meier curves showed that the high P4HA1 expression group had worse prognosis. (C) P4HA1 expression in 5-8F cells were verified by real-time qPCR. (D) P4HA1,AKT, HIF-1α, and PI3K expression in 5-8F cells were verified by western blot assay. (E) CCK-8 assay showed that P4HA1 could promote the proliferation of nasopharyngeal carcinoma cells. (F, G) Colony formation assay showed that P4HA1 could promote the proliferation of nasopharyngeal carcinoma cells. (H, I) Transwell assay showed that P4HA1 could promote nasopharyngeal carcinoma metastasis.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Xiong G, et al. Collagen prolyl 4-hydroxylase 1 is essential for HIF-1α stabilization and TNBC chemoresistance. Nat. Commun. 2018;9:4456. doi: 10.1038/s41467-018-06893-9. - DOI - PMC - PubMed
    1. Ramshaw JA, Shah NK, Brodsky B. Gly-X-Y tripeptide frequencies in collagen: A context for host-guest triple-helical peptides. J. Struct. Biol. 1998;122:86–91. doi: 10.1006/jsbi.1998.3977. - DOI - PubMed
    1. Gorres KL, Raines RT. Prolyl 4-hydroxylase. Crit. Rev. Biochem. Mol. Biol. 2010;45:106–124. doi: 10.3109/10409231003627991. - DOI - PMC - PubMed
    1. Myllyharju J. Prolyl 4-hydroxylases, the key enzymes of collagen biosynthesis. Matrix. Biol. 2003;22:15–24. doi: 10.1016/s0945-053x(03)00006-4. - DOI - PubMed
    1. Grimmer C, et al. Regulation of type II collagen synthesis during osteoarthritis by prolyl-4-hydroxylases: Possible influence of low oxygen levels. Am. J. Pathol. 2006;169:491–502. doi: 10.2353/ajpath.2006.050738. - DOI - PMC - PubMed

MeSH terms

Substances