Abstract
Oral squamous cell carcinoma (OSCC), a kind of malignant cancer, is associated with increasing morbidity and mortality. Patients with different genetic ancestries may respond differently to clinical treatment. The limited understanding of the influence of genetic ancestry and genetic characteristics on OSCC impedes the development of precision medicine. To provide a reference for clinical treatment, this study comprehensively analyzed multigenomic differences in OSCC patients with different genetic ancestries and their impact on prognosis. An analysis of data from OSCC patients with different genetic ancestries in The Cancer Genome Atlas (TCGA) showed that the overall survival (OS) of African (AFR) patients was lower than that of primarily European (EUR) patients, and differences were also observed in the tumor–stroma ratio (TSR) and tumor-infiltrating lymphocytes (TILs), which are associated with prognosis. FAT1 is a key mutant gene in OSCC, and it has inconsistent effects on clinical evolution for patients with diverse genetic characteristics. PIKfyve and CAPN9 showed a significant difference in mutation frequency between EUR and AFR; PIKfyve was related to Ki-67 expression, suggesting that it could promote tumor proliferation, and CAPN9 was related to the expression of Bcl-2, promoting tumor cell apoptosis. A variant methylation locus, cg20469139, was correlated with the levels of PD-L1 and Caspase-7 and modulated tumor cell apoptosis. A novel ceRNA model was constructed based on genetic ancestries, and it could accurately evaluate patient prognosis. More importantly, although T cell dysfunction scores could determine the potential of tumor immune escape, the efficacy was obviously affected by patients’ genetic ancestries. To provide patients with more precise, personalized therapy and to further improve their quality of life and 5-year survival rate, the influence of genetic ancestry should be fully considered when selecting treatments.
Highlights
Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the oral cavity or head and neck region and is listed as the eighth most common cancer type in the world (Carnielli et al, 2018; Wang et al, 2021), accounting for approximately 90% of oral tumors and 3% of systemic malignant tumors (Zhao et al, 2020; Lu et al, 2021)
According to the latest Global Cancer Incidence, the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer (IARC), newly developed OSCC originating from the alveolar ridge, buccal mucosa, bottom of the oral cavity, upper jaw, tongue, and other parts of the mouth accounted for 377,713 cases worldwide, with a death toll of 177,757 (Sung et al, 2021), which is much higher than the 300,000 new cases and 145,000 deaths reported globally in 2012 (Ferlay et al, 2015)
We analyzed the genetic ancestries of OSCC patients in the The Cancer Genome Atlas (TCGA) database
Summary
Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the oral cavity or head and neck region and is listed as the eighth most common cancer type in the world (Carnielli et al, 2018; Wang et al, 2021), accounting for approximately 90% of oral tumors and 3% of systemic malignant tumors (Zhao et al, 2020; Lu et al, 2021). Due to exposure to different living environments or different pathogenic or nonpathogenic factors, their tumor morbidities, outcomes, prognoses, and pathogenic molecular characteristics differ (Yang et al, 2011; Vineis and Fecht, 2018; Ou et al, 2020). Previous studies have mainly focused on molecular differences between normal oral tissues and tumor tissues and their effects (Chen et al, 2020; Yin et al, 2020). No report is available on differences in molecular-genomic characteristics of OSCC patients of different genetic ancestries. We intend to use a comprehensive cross-platform and multigenomic analysis, including hematoxylin–eosin (HE) staining, somatic mutations, methylation, RNA expression, immune infiltration, and immune response data, to analyze the differences in the prognoses of OSCC patients of various genetic ancestries, especially primarily European (EUR) and African (AFR). We sought to exploit these results to improve our understanding of the molecular and cellular effects of ancestry across clinical evolution and the relationship between ancestry and clinical treatment and prognosis to provide new options for the effective precision treatment of OSCC patients (Figure 1)
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