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Identification of a novel prognostic ADME-related signature associated with tumor immunity for aiding therapy in head and neck squamous cell carcinoma

Abstract

The genes that control drug absorption, distribution, metabolism, and excretion (ADME) are also involved in carcinogenesis, cancer progression, and chemoresistance. However, no studies have systematically investigated the clinical significance and underlying functions of ADME genes in head and neck squamous cell carcinoma. Herein, we comprehensively explored the ADME genes in this disease, constructed and validated as a prognostic ADME gene signature (ADMEGS), using three ADME genes (ABCB1, ALDH1B1, and PON2) utilizing multiple datasets, including the training and test sets of The Cancer Genome Atlas and the Gene Expression Omnibus validation set. Moreover, we analyzed the relationship between the ADMEGS and clinical parameters, tumor immunity, and therapeutic response. We found that the ADMEGS was significantly correlated with the clinical, T, and N stages. Additionally, we were able to effectively differentiate tumor immune scores, immune cell infiltration statuses, and treatment responses based on the ADMEGS. As such, ADMEGS may be promising predictors for clinical outcome, tumor immunity, and treatment response.

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Fig. 1: Establishment of the ADMEGS using 3 prognostic ADME genes in HNSCC.
Fig. 2: Prognostic performance of the ADMEGS.
Fig. 3: Clinical evaluation by the ADMEGS in HNSCC patients.
Fig. 4: Function enrichment analysis in the ADMEGSlow and ADMEGShigh groups of the TCGA dataset.
Fig. 5: Estimation of tumor immune score and tumor-infiltrating immune cells by the ADMEGS.
Fig. 6: Correlation of the three ADMEGS genes with the subpopulations of T cells and B cells in the TCGA dataset.
Fig. 7: Estimation of immunotherapeutic targets by ADMEGS.

Data availability

The HTSeq-FPKM and clinical data of HNSCC datasets can be obtained from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/) and Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/).

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Funding

This study was supported by the National Natural Science Foundation of China (Nos. 81974424, 81772903), the National Key Research and Development Project of China (Nos. 2020YFC1316900, 2020YFC1316901), the Hunan provincial Health and Family Planning Commission (Nos. B202307019501, 202103030223, 20201947, B20180186), the Hunan Provincial Natural Science Foundation of China (Nos. 2021JJ40502, 2019JJ50547), and the Hunan Province Science and Technology Department (No. 2017Sk50206).

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ZL and XZ designed the study and approved the manuscript; JW contributed to the data analysis and experiment execution; JW and JY wrote the manuscript; YT conducted data interpretations and depicted the figures.

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Correspondence to Juncheng Wang or Jing Yang.

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Liu, Z., Tian, Y., Zhang, X. et al. Identification of a novel prognostic ADME-related signature associated with tumor immunity for aiding therapy in head and neck squamous cell carcinoma. Cancer Gene Ther (2022). https://doi.org/10.1038/s41417-022-00557-z

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