Journal of gastrointestinal oncology · 2026
Identification of an autophagy-related prognostic signature and validation of WDR45 in colorectal cancer.
СтатьяНазвание 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.
Qin Cuiying, He Youwu, Wu Wenling, Gan Binliang, Luo Xinning, Feng Xianjie, Deng Ganlu
Аннотация
BACKGROUND: Colorectal cancer (CRC) is a common cancer and leading cause of cancer-related death with an insidious onset and a high recurrence rate after surgery. Autophagy has been shown to be closely related to the progression of CRC. This study aimed to identify novel biomarkers based on autophagy-related genes (ATGs).
METHODS: RNA-sequencing and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database, and combined with ATG data to identify differentially expressed autophagy-related genes (DEATGs). A prognostic risk model of the DEATGs was constructed using multivariable Cox regression. Genomic alteration, DNA methylation, and the tumor mutational burden (TMB) of the hub ATGs were analyzed, along with pan-cancer expression, interaction proteins, prognostic values, pharmaceutical sensitivity, and immune infiltration. The expression of the hub ATGs was verified in local CRC samples and cell lines. Functional assays were performed. The expression of autophagy-related proteins was detected.
RESULTS: A total of 320 DEATGs were identified, and a two-gene prognostic signature (comprising WDR45 and EGFR) was developed. The hub ATG WDR45 was highly expressed in various cancers and acted as an independent predictor of CRC. WDR45 expression was associated with putative genetic alterations, TP53 mutations, promoter methylation, and the TMB. WDR45 expression was also negatively correlated with the sensitivity of 74 anti-cancer drugs. WDR45 was closely related to the infiltration of regulatory T cells (Tregs), CD4+ T cells, and macrophages. The aberrant upregulation of WDR45 in CRC was confirmed in 46 paired tissue specimens and five cell lines. The knockdown of WDR45 suppressed the proliferation of CRC cells, and inhibited cell autophagy.
CONCLUSIONS: This study constructed an ATG-based signature that accurately predicted the prognosis of CRC patients. It also identified WDR45 as a novel biomarker and target for CRC.
METHODS: RNA-sequencing and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database, and combined with ATG data to identify differentially expressed autophagy-related genes (DEATGs). A prognostic risk model of the DEATGs was constructed using multivariable Cox regression. Genomic alteration, DNA methylation, and the tumor mutational burden (TMB) of the hub ATGs were analyzed, along with pan-cancer expression, interaction proteins, prognostic values, pharmaceutical sensitivity, and immune infiltration. The expression of the hub ATGs was verified in local CRC samples and cell lines. Functional assays were performed. The expression of autophagy-related proteins was detected.
RESULTS: A total of 320 DEATGs were identified, and a two-gene prognostic signature (comprising WDR45 and EGFR) was developed. The hub ATG WDR45 was highly expressed in various cancers and acted as an independent predictor of CRC. WDR45 expression was associated with putative genetic alterations, TP53 mutations, promoter methylation, and the TMB. WDR45 expression was also negatively correlated with the sensitivity of 74 anti-cancer drugs. WDR45 was closely related to the infiltration of regulatory T cells (Tregs), CD4+ T cells, and macrophages. The aberrant upregulation of WDR45 in CRC was confirmed in 46 paired tissue specimens and five cell lines. The knockdown of WDR45 suppressed the proliferation of CRC cells, and inhibited cell autophagy.
CONCLUSIONS: This study constructed an ATG-based signature that accurately predicted the prognosis of CRC patients. It also identified WDR45 as a novel biomarker and target for CRC.