Prognostic prediction of head and neck squamous cell carcinoma: Construction of cuproptosis‐related long non‐coding RNA signature

Abstract

Background

Recently, a new type of programmed cell death, cuproptosis, has been identified to play important role in the progression of tumors. We constructed a cuproptosis‐related long non‐coding RNA (lncRNA) signature to predict the prognostic significance for head and neck squamous cell carcinoma (HNSCC).

Methods

The risk model was developed based on differentially expressed lncRNAs associated with cuproptosis. Principal component analysis was used to assess the validity. The Kaplan–Meier curves were analyzed to compare the overall survival (OS), disease‐specific survival (DSS), and progression‐free survival (PFS) values. The multivariate and univariate Cox regression analyses were used to evaluate the prognostic efficiency. Furthermore, the functional enrichment, immune cell infiltration, tumor mutation burden (TMB), and sensitivity toward chemotherapy were also explored.

Results

Six cuproptosis‐related lncRNAs (AL109936.2, CDKN2A‐DT, AC090587.1, KLF3‐AS1, AL133395.1, and LINC01063) were identified to construct the independent prognostic predictor for HNSCC. The area under the curve and C‐index values obtained using the risk model were higher than the values corresponding to the clinical factors. Analysis of Kaplan–Meier curves indicated that the OS, PFS, and DSS time recorded for the patients in the low‐risk group were higher than the corresponding values recorded for the patients belonging to the high‐risk group. By functional enrichment analysis, we observed that differentially expressed genes were enriched in the immune response and tumor‐associated pathways. The patients characterized by a low‐risk score exhibited better immune cell infiltration than the patients belonging to the other group. We also observed that the sensitivity of the individuals belonging to the low‐risk group to chemotherapeutic agents (cisplatin, docetaxel, and paclitaxel) was higher than the sensitivity of those in the other group.

Conclusions

A cuproptosis‐related lncRNA‐based signature that functioned as an independent prognosis predictor for HNSCC patients was constructed. The chemosensitivity of individual patients can be potentially predicted using this signature.

Abstract

In this study, HNSCC clinical data and cuproptosis‐associated genes data were extracted from the public database. Prognostic differential genes were screened, and six cuproptosis‐associated LncRNAs signature was constructed. The developed signature was characterized by an independent prognostic value for the case of the total HNSCC cohort. The survival duration of the patients suffering from HNSCC and characterized by a high risk score was shorter than the survival time recorded for the patients characterized by low‐risk scores. The prognosis for the low‐risk score samples was better than the prognosis for the high‐risk score samples belonging to the stage III + IV subgroups. Enrichment of several immune‐related biological processes was observed in cuproptosis‐related lncRNAs by GO and KEGG analysis; The checkpoint, human leukocyte antigen (HLA), T cell co‐stimulation, inflammation‐promoting, and type II interferon response pathways were enriched in the low‐risk group. The low‐TMB group patients were more likely to survive for a longer period of time than those in the high‐TMB group. The high‐risk patients were more sensitive to cisplatin‐, docetaxel‐, and paclitaxel‐based treatment schemes.