Novel hypoxia-immune biomarkers predict response to neoadjuvant chemotherapy in patients with laryngo-hypopharyngeal cancer.

BACKGROUND

The hypoxic immune microenvironment has clinical significance in predicting sensitivity to neoadjuvant chemotherapy (NAC) in patients with laryngo-hypopharyngeal cancer (LHC).

METHODS

In this study, RNA sequencing was performed to screen out differentially expressed genes (DEGs). Logistic regression analysis was used to construct a predictive model. Receiver operating characteristic (ROC) curves were used to evaluate the sensitivity and specificity. Kaplan-Meier survival analysis was conducted to investigate the differences in overall survival (OS) and progression-free survival (PFS) between different risk groups. Immune infiltration analysis was performed using the "ssGSEA" method. The association between biomarkers and drug sensitivity was assessed using the CellMiner database.

RESULTS

We screened 40 hypoxia immunity-related DEGs and constructed a five-gene prediction model with an area under the curve of 0.854. The high-risk group had a worse OS and PFS than the low-risk group in both our data and TCGA-HNSC external data set. Furthermore, immune cell infiltration played a role in the efficacy of NAC, specifically through its impact on the level of natural killer cell infiltration and migration ability. Finally, we validated gene expression in an independent clinical cohort. We also observed that patients with increased AREG expression showed sensitivity to the anticancer therapeutic drugs afatinib and sapitinib.

CONCLUSIONS

Our hypoxia-immune panel can accurately predict response to NAC and OS in patients with LHC and may have implications for the development of novel biomarkers and targeted therapies.

TRIAL REGISTRATION: This study was fully endorsed by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (protocol code: TREC2022-KY018.R1, approval date: 2022-4-21).