Роль инсулиноподобного фактора роста, провоспалительных и противовоспалительных цитокинов, факторов транскрипции и адипокинов в развитии гепатоцеллюлярной карциномы при метаболическом синдроме

Противоречивые данные о роли метаболического синдрома (МС) в развитии гепатоцеллюлярной карциномы (ГЦК) актуализируют изучение влияния молекулярных факторов, имеющих значение при МС в развитии ГЦК, что и стало целью нашего обзора. Были изучены и проанализированы публикации (научные статьи и обзоры) за последние 10 лет по базам данных Web of Science, Scopus, PubMed, РИНЦ. В качестве поисковых фраз использовались «метаболический синдром и неалкогольная жировая болезнь печени», «метаболический синдром и неалкогольный стеатогепатит», «метаболический синдром и гепатоцеллюлярная карцинома». Общее количество изученных публикаций по всем базам данных составило более 570 единиц, при этом в обзоре представлены наиболее значимые результаты на современном этапе. Инсулинорезистентность и ожирение через развитие системного хронического воспалительного состояния приводят к усилению воспаления и фиброза в печени, которые являются продромальными признаками гепатоканцерогенеза, увеличивают выработку инсулиноподобного фактора роста-1 и нарушают регуляцию пути инсулиноподобного фактора роста. У людей с ГЦК выявлялась гиперэкспрессия ИФР-2. ИФР-связывающие белки из-за сниженной биодоступности свободных ИФР-1 и ИФР-2 в кровотоке способны ингибировать рост ГЦК. При МС обнаруживается провоспалительное состояние, которое обусловлено продукцией адипоцитами цитокинов (IL-6, IL-8, IL-1β, фактор некроза опухоли α (TNFα), VEGF и хемокиновых лигандов 2 и 5), которые рекрутируют иммунные клетки, способствуя ангиогенезу и усилению хронического воспаления. Факторы транскрипции (PPAR) участвуют в гепатоканцерогенезе, значимость разных факторов до конца не изучена. Лептин имеет положительное прогностическое значение при ГЦК, улучшая общую выживаемость, а висфатин оказывает негативное влияние на гепатоканцерогенез. Активация PAI-1 ингибирует прогрессирование ГЦК через стимуляцию PPARγ. Адипонектин может быть маркером прогноза при ГЦК, минимальная его концентрация в сыворотке, положительно коррелирует с более неблагоприятным прогнозом.

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