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. 2025 Mar;31(3):769-781.
doi: 10.1111/odi.15124. Epub 2024 Sep 17.

Prognostic impact of caspase-8 mutation in oral cavity squamous cell carcinoma

Hsueh-Ju Lu  1   2 , Chun-Wen Su  3   4 , Shih-Chi Su  5   6 , Lun-Ching Chang  7 , Ming-Fang Wu  1   2 , Chiao-Wen Lin  8   9 , Shun-Fa Yang  3   4
Affiliations

Prognostic impact of caspase-8 mutation in oral cavity squamous cell carcinoma

Hsueh-Ju Lu et al. Oral Dis. 2025 Mar.

Abstract

Objective: Identifying the drive genes and inhibiting their significant signals were persistently the main concepts in cancer treatment. However, for oral cavity squamous cell carcinoma (OCSCC), the most influential genes for overall survival (OS) remain unclear.

Methods: A total of 120 OCSCC patients with corresponding pathologic specimens were collected in Taiwan. Whole-exome sequencing was done and the prognostic impact of each gene was analyzed. TCGA database was used to validate.

Results: The incidences of caspase-8 mutation were 22.1% and 10.9% in the Taiwan and TCGA cohort, respectively. In the Taiwan cohort, caspase-8 mutation was the most significant independent for OS with an adjusted hazard ratio (HR) ([95% CI]: 3.83 [1.84-7.99]). It was validated by the TCGA database (HR [95% CI]: 1.51 [1.00-2.29]). The 5-year OSs of the patients with or without caspase-8 mutation were 38.1% vs. 75.3% (p < 0.001) (HR [95% CI]: 3.264 [1.645-6.438]) in the Taiwan cohort, and 26.1% vs. 49.0% (p = 0.048) (1.513 [1.001-2.288]) in the TCGA cohorts, respectively. Caspase-8 mutation was also individually associated with poor prognosis for TNM stage I/II/III/IV, respectively. CASP8 R127* and R494*, defined as pathogenic mutations in ClinVar, were presented in both cohorts.

Conclusions: Caspase-8 mutation was the most significant genetic alteration impacting prognosis.

Keywords: caspase‐8; TCGA; oral cavity squamous cell carcinoma; overall survival.

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References

REFERENCES

    1. Adkins, D., Ley, J., Neupane, P., Worden, F., Sacco, A. G., Palka, K., Grilley‐Olson, J. E., Ronald, M., Noha, N. S., Kathryn, T., Brian, A. V., Conor, E. S., Nabil, F. S., & Oppelt, P. (2019). Palbociclib and cetuximab in platinum‐resistant and in cetuximab‐resistant human papillomavirus‐unrelated head and neck cancer: A multicentre, multigroup, phase 2 trial. The Lancet Oncology, 20(9), 1295–1305. https://doi.org/10.1016/S1470‐2045(19)30405‐X
    1. Adzhubei, I., Jordan, D. M., & Sunyaev, S. R. (2013). Predicting functional effect of human missense mutations using PolyPhen‐2. Current Protocols in Human Genetics, 7, 20. https://doi.org/10.1002/0471142905.hg0720s76
    1. Akimov, Y., & Aittokallio, T. (2021). Re‐defining synthetic lethality by phenotypic profiling for precision oncology. Cell Chemical Biology, 28(3), 246–256. https://doi.org/10.1016/j.chembiol.2021.01.026
    1. Baselga, J., Cortes, J., Kim, S. B., Im, S. A., Hegg, R., Im, Y. H., Roman, L., Pedrini, J. L., Pienkowski, T., Knott, A., Clark, E., Benyunes, M. C., Ross, G., Swain, S. M., & CLEOPATRA Study Group. (2012). Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. The New England Journal of Medicine, 366(2), 109–119. https://doi.org/10.1056/NEJMoa1113216
    1. Campo, E., Jaffe, E. S., Cook, J. R., Quintanilla‐Martinez, L., Swerdlow, S. H., Anderson, K. C., Brousset, P., Cerroni, L., de Leval, L., Dirnhofer, S., Dogan, A., Feldman, A. L., Fend, F., Friedberg, J. W., Gaulard, P., Ghia, P., Horwitz, S. M., King, R. L., Salles, G., … Zelenetz, A. D. (2022). The international consensus classification of mature lymphoid neoplasms: A report from the clinical advisory committee. Blood, 140(11), 1229–1253. https://doi.org/10.1182/blood.2022015851

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