Predicting radiotherapy efficacy and prognosis in tongue squamous cell carcinoma through an in-depth analysis of a radiosensitivity gene signature

Jinzhi Lai; Hainan Yang; Junjun Chen; Shoubo Chen; Xiaofang Chen

doi:10.3389/fonc.2024.1334747

Frontiers in Oncology (Aug 2024)

Predicting radiotherapy efficacy and prognosis in tongue squamous cell carcinoma through an in-depth analysis of a radiosensitivity gene signature

Jinzhi Lai,
Hainan Yang,
Junjun Chen,
Shoubo Chen,
Xiaofang Chen

Affiliations

Jinzhi Lai: Department of Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
Hainan Yang: Department of Ultrasound, First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
Junjun Chen: National Health Commission (NHC) Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital of Nanchang Medical College, Nanchang, Jiangxi, China
Shoubo Chen: Department of Orthopaedics, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
Xiaofang Chen: Department of Otolaryngology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

DOI: https://doi.org/10.3389/fonc.2024.1334747
Journal volume & issue: Vol. 14

Abstract

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BackgroundTongue squamous cell carcinoma (TSCC) is a prevalent tumor that affects many people worldwide. Radiotherapy is a common treatment option, but its efficacy varies greatly. This study seeks to validate the identified gene signature associated with radiosensitivity in TSCC, and its potential in predicting radiotherapy response and prognosis.MethodsWe analyzed 122 TSCC patients from TCGA database using the radiosensitivity signature and classified them into radiosensitive (RS) and radioresistant (RR) groups. Immune infiltration analysis methods were applied to investigate the immune status between different subgroups. Immunophenotype Score (IPS) and pRRophetic algorithm were employed to estimate the efficiency of treatment. A radioresistant TSCC cell line was established by gradually increasing radiation doses. Cell radiosensitivity was evaluated using the CCK-8 and colony formation assays. The expression of radiosensitivity-related genes was validated by qRT-PCR.ResultsOur study validated the predictive capacity of a previously identified “31-gene signature” in the TCGA-TSCC cohort, which effectively stratified patients into RS and RR groups. We observed that the RS group exhibited superior overall survival and progression-free survival rates relative to the RR group when treated with radiotherapy. The RS group was significantly enriched in most immune-related hallmark pathways, and may therefore benefit from immune checkpoint inhibitors. However, the RS group displayed lower sensitivity to first-line chemotherapy. A radioresistant TSCC cell line (CAL-27R) exhibited increased clonogenic potential and cell viability following irradiation, accompanied by downregulation of three radiosensitivity-related genes compared to its parental non-resistant cell (CAL-27). In addition, we constructed and validated a radiosensitivity-related prognostic index (PI) using 4 radiosensitivity-related genes associated with TSCC prognosis.ConclusionWe assessed the ability of the radiosensitivity gene signature to predict outcomes in TSCC patients. our research provided valuable insights into the molecular pathways associated with radiosensitivity in TSCC and offered clinicians a practical tool to predict patient radiotherapy effectiveness and prognosis.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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