Molecular medicine (Cambridge, Mass.) · 2022
Molecular landscape of IDH-mutant astrocytoma and oligodendroglioma grade 2 indicate tumor purity as an underlying genomic factor.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhao Binghao, Xia Yu, Yang Fengchun, Wang Yaning, Wang Yuekun, Wang Yadong, Dai Congxin, Wang Yu, Ma Wenbin
Аннотация
BACKGROUND: IDH-mutant astrocytoma and oligodendroglioma have an indolent natural history and are recognized as distinct entities of neoplasms. There is little knowledge on the molecular differences between IDH-mutant astrocytoma and oligodendroglioma grade 2. Therefore, we investigated the multiomics and clinical data regarding these two types of tumors.
METHOD: In silico analyses were performed around mRNA, somatic mutations, copy number alternations (CNAs), DNA methylation, microRNA (miRNA), epigenetics, immune microenvironment characterization and clinical features of the two types of gliomas. A diagnostic model incorporating tumor purity was further established using machine learning algorithms, and the predictive value was evaluated by receiver operative characteristic curves.
RESULTS: Both types of gliomas shared chromosomal instability, and astrocytomas exhibited increased total CNAs compared to oligodendrogliomas. Oligodendrogliomas displayed distinct chromosome 4 (chr 4) loss, and subtyping of chr 7 gain/chr 4 loss (+ 7/- 4) presented the worst survival (P = 0.004) and progression-free interval (PFI) (P < 0.001). In DNA damage signatures, oligodendroglioma had a higher subclonal genome fraction (P < 0.001) and tumor purity (P = 0.001), and astrocytoma had a higher aneuploidy score (P < 0.001). Furthermore, astrocytomas exhibited inflamed immune cell infiltration, activated T cells and a potential response to immune checkpoint inhibitors (ICIs), while oligodendrogliomas were more homogeneous with increased tumor purity and decreased aggression. The tumor purity-involved diagnostic model exhibited great accuracy in identifying astrocytoma and oligodendroglioma.
CONCLUSION: This study addresses the similarities and differences between IDH-mutant astrocytoma and oligodendroglioma grade 2 and facilitates a deeper understanding of their molecular features, immune microenvironment, tumor purity and prognosis. The diagnostic tool developed using machine learning may offer support for clinical decisions.
METHOD: In silico analyses were performed around mRNA, somatic mutations, copy number alternations (CNAs), DNA methylation, microRNA (miRNA), epigenetics, immune microenvironment characterization and clinical features of the two types of gliomas. A diagnostic model incorporating tumor purity was further established using machine learning algorithms, and the predictive value was evaluated by receiver operative characteristic curves.
RESULTS: Both types of gliomas shared chromosomal instability, and astrocytomas exhibited increased total CNAs compared to oligodendrogliomas. Oligodendrogliomas displayed distinct chromosome 4 (chr 4) loss, and subtyping of chr 7 gain/chr 4 loss (+ 7/- 4) presented the worst survival (P = 0.004) and progression-free interval (PFI) (P < 0.001). In DNA damage signatures, oligodendroglioma had a higher subclonal genome fraction (P < 0.001) and tumor purity (P = 0.001), and astrocytoma had a higher aneuploidy score (P < 0.001). Furthermore, astrocytomas exhibited inflamed immune cell infiltration, activated T cells and a potential response to immune checkpoint inhibitors (ICIs), while oligodendrogliomas were more homogeneous with increased tumor purity and decreased aggression. The tumor purity-involved diagnostic model exhibited great accuracy in identifying astrocytoma and oligodendroglioma.
CONCLUSION: This study addresses the similarities and differences between IDH-mutant astrocytoma and oligodendroglioma grade 2 and facilitates a deeper understanding of their molecular features, immune microenvironment, tumor purity and prognosis. The diagnostic tool developed using machine learning may offer support for clinical decisions.