Abstract
Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and has a high mortality. Ferroptosis, an iron-dependent form of programmed cell death, plays a crucial role in tumor suppression and chemotherapy resistance in cancer. However, the prognostic and clinical values of ferroptosis-related genes (FRGs) in HNSCC remain to be further explored. In the current study, we constructed a ferroptosis-related prognostic model based on the Cancer Genome Atlas database and then explored its prognostic and clinical values in HNSCC via a series of bioinformatics analyses. As a result, we built a four-gene prognostic signature, including FTH1, BNIP3, TRIB3, and SLC2A3. Survival analysis showed that the high-risk group presented significantly poorer overall survival than the low-risk group. Moreover, the ferroptosis-related signature was found to be an independent prognostic predictor with high accuracy in survival prediction for HNSCC. According to immunity analyses, we found that the low-risk group had higher anti-tumor immune infiltration cells and higher expression of immune checkpoint molecules and meanwhile corelated more closely with some anti-tumor immune functions. Meanwhile, all the above results were validated in the independent HSNCC cohort GSE65858. Besides, the signature was found to be remarkably correlated with sensitivity of common chemotherapy drugs for HNSCC patients and the expression levels of signature genes were also significantly associated with drug sensitivity to cancer cells. Overall, we built an effective ferroptosis-related prognostic signature, which could predict the prognosis and help clinicians to perform individualized treatment strategy for HNSCC patients.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the eighth most common cancer worldwide, accounts for the majority of head and neck cancers and has a high mortality rate of 40–50% (Bray et al, 2018; Moskovitz et al, 2018)
As a process of cell death, ferroptosis plays a crucial role in tumorigenesis and has the ability to strongly inhibit tumor growth (Lu et al, 2017)
As it has been shown that inhibition of ferroptosis-related genes (FRGs) can overcome cisplatin resistance in HNSCC via the induction of ferroptosis (Roh et al, 2017; Kim et al, 2018; Lee et al, 2020), we explored the mRNA expression levels of 187 retrieved FRGs in HNSCC and built a novel prognostic model based on these genes
Summary
Head and neck squamous cell carcinoma (HNSCC) is the eighth most common cancer worldwide, accounts for the majority of head and neck cancers and has a high mortality rate of 40–50% (Bray et al, 2018; Moskovitz et al, 2018). A Ferroptosis-Related Signature in HNSCC clinical features have been used as prognostic factors to develop efficient and personalized therapeutic strategies. The suppression of these ferroptosisrelated genes (FRGs, such as GLRX5, NRF2, and CISD2) can overcome the resistance to chemotherapy in HNSCC via promoting ferroptosis and may be useful to provide new treatment strategies for patients with drug resistance (Roh et al, 2017; Kim et al, 2018; Lee et al, 2020). Previous studies have shown that some drugs can cause head and neck cancer cell death through inducing ferroptosis (Lin et al, 2016; Kim et al, 2018). Our results may provide a novel predictive tool and treatment option for patients with HNSCC
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