Construction of a 5-methylcytosine-Related Molecular Signature to Inform the Prognosis and Immunotherapy of Lung Squamous Cell Carcinoma

ABSTRACT

Background

Methylation of cytosine residues resulting in 5-methylcytosine (5-mC) is an important epigenetic modification associated with tumorigenesis. The present study explored the relationship between methylation, prognosis, and immunotherapy of patients suffering from lung squamous cell carcinoma (LUSC).

Methods

RNA sequencing data and corresponding clinical information were downloaded, and preprocessed, and unsupervised consistent cluster analysis was used to identify 5-mC-related clusters and gene clusters. 5-mC scores were calculated using principal component analysis, and a Boruta algorithm was used to evaluate the relationship between tumor mutation burden (TMB), immune checkpoint inhibitor response, and prognosis of individual LUSC patients.

Results

: Two 5-mC clusters and three gene clusters with different prognoses were identified. Patients with higher 5-mC scores showed worse prognoses, which was confirmed in multiple cohorts. Some immune-related biological functions and pathways were enriched in the high-5-mC score subtype.

Conclusion

The 5-mC score is a potential biomarker independent of TMB, which can be a decisive factor regarding immune treatment responses. Further, patients with low 5-mC scores may respond better to immunotherapy. The 5-mC score can thus be used as a potential biomarker for the prognosis of LUSC patients and their response to immunotherapy.

KEYWORDS:

• Lung squamous cell carcinoma
• 5-methylcytosine
• prognosis
• immunotherapy
• tumor mutation burden

Acknowledgment

We would like to thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Data availability statement

All data generated or analyzed in this study are from TCGA and GEO database.

Ethics statement

This study is a retrospective analysis without any intervention and thus did not require informed consent.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737159.2022.2131396

Additional information

Funding

The Science and Technology Department of Sichuan Program (2021YJ0470). The First Affiliated Hospital of Chengdu Medical College program (CYFY2019GLPHX04)