Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66704810.31857/S0016675823110103NMECVYГЕНЕТИКА ЧЕЛОВЕКАMolecular Landscape of Oral Cancer in Young AdultsМолекулярный ландшафт рака полости рта у молодых пациентовProstakishinaE. A.ПростакишинаЕ. А.elenakolegova@oncology.tomsk.ruDampilovaT. D.ДампиловаТ. Д.elenakolegova@oncology.tomsk.ruKononovaL. A.КононоваЛ. А.elenakolegova@oncology.tomsk.ruIamshchikovP. S.ЯмщиковП. С.elenakolegova@oncology.tomsk.ruPatyshevaM. R.ПатышеваМ. Р.elenakolegova@oncology.tomsk.ruKolegovaE. S.КолеговаЕ. С.elenakolegova@oncology.tomsk.ruChoinzonovE. L.ЧойнзоновЕ. Л.elenakolegova@oncology.tomsk.ruDenisovE. V.ДенисовЕ. В.elenakolegova@oncology.tomsk.ruCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукFederal Siberian State Medical UniversityСибирский государственный медицинский университет0111202359111290130226022025Copyright ©; 2023, Е.А. Простакишина, Т.Д. Дампилова, Л.А. Кононова, П.С. Ямщиков, М.Р. Патышева, Е.С. Колегова, Е.Л. Чойнзонов, Е.В. ДенисовCopyright ©; 2023, Е.А. Простакишина, Т.Д. Дампилова, Л.А. Кононова, П.С. Ямщиков, М.Р. Патышева, Е.С. Колегова, Е.Л. Чойнзонов, Е.В. Денисов2023Е.А. Простакишина, Т.Д. Дампилова, Л.А. Кононова, П.С. Ямщиков, М.Р. Патышева, Е.С. Колегова, Е.Л. Чойнзонов, Е.В. ДенисовЕ.А. Простакишина, Т.Д. Дампилова, Л.А. Кононова, П.С. Ямщиков, М.Р. Патышева, Е.С. Колегова, Е.Л. Чойнзонов, Е.В. Денисовhttps://transsyst.ru/0016-6758/article/view/667048

Oral cancer (OC) is the most common cancer of the head and neck. Tongue cancer (TC) is the most frequently diagnosed form of OC and is characterized by a high aggressiveness and progression. OC and TC are considered diseases of the elderly, but the incidence among young patients (under 45 years) is increasing every year. The etiological factors and pathogenetic mechanisms of early-onset OC and TC remain unclear. In the present study, based on The Cancer Genome Atlas database, we analyzed the mutational profile, methylome, transcriptome, proteome, and microbiome of OC and TC in young adults (n = 127) compared with older patients. Early-onset OC and TC demonstrated a decrease in the mutation burden, activation of Rap1, PI3K-Akt, MAPK, cGMP-PKG signaling pathways and signaling of Fc-gamma R-mediated phagocytosis, and a specific microbiome profile. In contrast to OC, TC was characterized by activation of such signaling pathways as JAK-STAT, immune response to infectious and parasitic diseases, and PD-L1/PD-1-mediated immunosuppression and inhibition of phagocytosis signaling. The obtained results indicate that early-onset OC demonstrates molecular features different from those in elderly patients, while TC differs from OC in molecular profile and should probably be considered a separate clinical form.

Рак полости рта (РПР) – наиболее распространенный тип злокачественных новообразований головы и шеи. При этом рак языка (РЯ) представляет собой наиболее часто встречающуюся форму РПР и характеризуется более агрессивным течением и высокой вероятностью прогрессирования. РПР и РЯ считаются заболеваниями пожилых людей, однако их встречаемость среди лиц моложе 45 лет растет с каждым годом. Этиологические факторы и патогенетические механизмы молодого рака неизвестны. В настоящей работе на основании данных базы Атласа генома рака изучены особенности мутационного профиля, метилома, транскриптома, протеома и микробиома РПР и РЯ у молодых пациентов (n = 127) по сравнению с возрастными больными. В ткани РПР и РЯ обнаружены снижение мутационной нагрузки, активация Rap1, PI3K-Akt, MAPK, cGMP-PKG сигнальных путей и сигналинга Fc-гамма R-опосредованного фагоцитоза и специфический микробиомный профиль. В отличие от РПР для РЯ характерны активация сигнальных путей JAK-STAT, иммунного ответа на инфекционные и паразитарные заболевания и PD-L1/PD-1-опосредованной иммуносупрессии и ингибирование сигналинга фагоцитоза. Полученные результаты свидетельствуют о том, что РПР у молодых пациентов обладает молекулярными особенностями, отличными от таковых у больных старше 45 лет, при этом РЯ отличается от других локализаций РПР по молекулярному профилю и, вероятно, должен рассматриваться как отдельная клиническая форма.

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