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Prognostic Significance of the BIRC2-BIRC3 Gene Signature in Head and Neck Squamous Cell Carcinoma.


ABSTRACT:

Background/aim

Head and neck squamous cell carcinoma (HNSCC) has poor prognosis, with survival rates that have not significantly improved over the past several decades. Therefore, prediction of HNSCC prognosis is of clinical importance. Baculoviral IAP Repeat containing 2 (BIRC2) and Baculoviral IAP Repeat containing 3 (BIRC3) are involved in oncogenic activity by modulating cell proliferation, apoptosis and invasion in HNSCC. This study aimed to develop and validate a predictive gene signature for BIRC2 and BIRC3.

Materials and methods

The genomic copy number and gene expression for BIRC2 and BIRC3 were systematically explored in patients with HNSCC to investigate the clinical relevance of BIRC2 and BIRC3 activation. A prognostic signature was developed based on correlations associated with BIRC2 and BIRC3 mRNA expression and copy number alterations. Hierarchical clustering was used to classify the clusters (Clusters 1 and 2). Moreover, independent validation of the BIRC2-BIRC3 gene signature was performed using the Leipzig, MDACC, FHCRC, and KHU datasets. To explore the biological functions of the BIRC2-BIRC3 gene signature, string analysis and pathway annotation were also performed.

Results

BIRC2-BIRC3 gene signature-derived cluster 2 patients exhibited significantly poor survival. This signature also predicted survival in three independent cohorts. Interestingly, the BIRC2-BIRC3 gene signature additionally permitted the identification of survival in advanced tumor stages with excellent accuracy in all three cohorts. Multivariate Cox regression analysis identified that the BIRC2-BIRC3 signature was an independent predictor associated with the survival of patients with HNSCC. Moreover, Inhibition of BIRC2 modulated the NF-B signaling pathway via upregulation of CBR1 expression.

Conclusion

The BIRC2-BIRC3 gene signature was found to be associated with the prognosis of HNSCC. Thus, BIRC2 and BIRC3 could be potential targets for improving HNSCC prognosis.

SUBMITTER: Lee MK 

PROVIDER: S-EPMC9353722 | biostudies-literature | 2022 Sep-Oct

REPOSITORIES: biostudies-literature

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Publications

Prognostic Significance of the <i>BIRC2-BIRC3</i> Gene Signature in Head and Neck Squamous Cell Carcinoma.

Lee Min Kyeong MK   Noh Joo Kyung JK   Woo Seon Rang SR   Kong Moonkyoo M   Lee Young Chan YC   Lee Jung Woo JW   Ko Seong-Gyu SG   Eun Young-Gyu YG  

Cancer genomics & proteomics 20220901 5


<h4>Background/aim</h4>Head and neck squamous cell carcinoma (HNSCC) has poor prognosis, with survival rates that have not significantly improved over the past several decades. Therefore, prediction of HNSCC prognosis is of clinical importance. Baculoviral IAP Repeat containing 2 (BIRC2) and Baculoviral IAP Repeat containing 3 (BIRC3) are involved in oncogenic activity by modulating cell proliferation, apoptosis and invasion in HNSCC. This study aimed to develop and validate a predictive gene si  ...[more]

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