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A seven-gene signature to predict the prognosis of oral squamous cell carcinoma

Oncogene volume 40, pages 3859–3869 (2021)Cite this article

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Abstract

The prognosis of oral squamous cell carcinoma (OSCC) patients remains poor without implemented biomarkers in the clinical routine practice to help in the patient’s management. With this study we aimed to identify specific prognostic biomarkers for OSCC using a whole genome technology as well as to verify the clinical utility of a head and neck cancer-specific multiplex ligation-dependent probe amplification (MLPA) panel. A genomic characterization of tumor samples from 62 OSCC patients was performed using array comparative genomic hybridization (aCGH) and a more straightforward and cost-effective molecular technology, MLPA. The identification of a genomic signature and prognosis biomarkers was carried out by applying several statistical methods. With aCGH we observed that the chromosomes most commonly altered were 3p, 3q, 5q, 6p, 7q, 8p, 8q, 11q, 15q, 17q, and 18q. The MLPA results showed that the chromosomes with a higher frequency of alterations were 3p, 3q, 8p, 8q, and 11q. We identified a genomic signature with seven genes OCLN (3p21.31), CLDN16 (3q29), SCRIB (3q29), IKBKB (3q22.3), PAK2 (8q22.3), PIK3CB (3q28), and YWHAZ (8q24.3) that together allow to differentiate the patients that developed metastases or relapses after primary tumor treatment, with an overall accuracy of 79%. Amplification of PIK3CB as a predictor of metastases or relapses development was validated using TCGA data. This amplified gene showed a reduction in more than 5 years in the median survival of the patients. The identified biomarkers might have a significant impact in the patients’ management and could leverage the OSCC precision medicine.

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Fig. 1: Circos plots representing the most frequent alterations detected by array CGH, in the OSCC cohort.
Fig. 2: Correlation between alterations in chromosomal arms presenting a fraction of alteration higher, in average, than 0.1.
Fig. 3: PCA using the selected 11 genes identified with aCGH technique.
Fig. 4: Kaplan–Meier survival curves relating to the PIK3CB gene, in the TCGA cohort.
Fig. 5: Frequency of copy number alterations detected by MLPA for the genes included in the HNC-specific probe panel.
Fig. 6: Frequency of copy number alterations detected by aCGH for the genes included in the HNC-specific probe panel.

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Data availability

The data from array-CGH analyses that support the findings of this study are openly available at https://apps.uc.pt/mypage/faculty/fcaramelo/en/oscc.

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Acknowledgements

We thank MRC-Holland for the MLPA P428-B1 probe panel.

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Author notes

  1. These authors contributed equally: Ilda Patrícia Ribeiro, Luísa Esteves

Authors and Affiliations

  1. University of Coimbra, Cytogenetics and Genomics Laboratory, Institute of Cellular and Molecular Biology, Faculty of Medicine, Coimbra, Portugal

    Ilda Patrícia Ribeiro, Luísa Esteves, Ana Santos, Joana Barbosa Melo & Isabel Marques Carreira

  2. University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Coimbra, Portugal

    Ilda Patrícia Ribeiro, Francisco Marques, Francisco Caramelo, Joana Barbosa Melo & Isabel Marques Carreira

  3. University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal

    Ilda Patrícia Ribeiro, Joana Barbosa Melo & Isabel Marques Carreira

  4. Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal

    Ilda Patrícia Ribeiro, Francisco Marques, Joana Barbosa Melo & Isabel Marques Carreira

  5. Maxillofacial Surgery Department, Coimbra Hospital and University Centre (CHUC), EPE, Coimbra, Portugal

    Leonor Barroso

  6. Department of Dentistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Francisco Marques

  7. Stomatology Unit, Coimbra Hospital and University Centre (CHUC), EPE, Coimbra, Portugal

    Francisco Marques

  8. University of Coimbra, Laboratory of Biostatistics and Medical Informatics, iCBR—Faculty of Medicine, Coimbra, Portugal

    Francisco Caramelo

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  1. Ilda Patrícia Ribeiro
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Correspondence to Isabel Marques Carreira.

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Ribeiro, I.P., Esteves, L., Santos, A. et al. A seven-gene signature to predict the prognosis of oral squamous cell carcinoma. Oncogene 40, 3859–3869 (2021). https://doi.org/10.1038/s41388-021-01806-5

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