Influence of m6A regulatory factor related to immune microenvironment on the prognosis of prostate cancer

m6A 调控因子与免疫微环境相关,对前列腺癌预后的影响

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Abstract

BACKGROUND: Prostate cancer (PC) is an epithelial malignant tumor that occurs in the prostate. N6 methylpurine (m6A) methylation regulates the tumor immune microenvironment. This study aimed to investigate the expression of m6A regulatory factor in PC and its relationship with prognosis. METHODS: PC tissues and adjacent tissues were collected from PC patients who underwent surgical resection. The content of m6A regulator YTH m6A RNA binding protein 1 (YTHDF1) and insulin-like growth factor binding protein 2 (IGFBP2) was examined using Immunohistochemistry (IHC). The survival prognosis was predicted through Kaplan Meier survival curve. The patients were grouped into good and poor prognosis group according to whether recurrence and metastasis occurred within the 62 months of follow-up. Logistic regression analysis was adopted to analyze the risk factors. RESULTS: YTHDF1 and IGFBP2 were localized in the cytoplasm of PC tissues. The positive expression rate of YTHDF1 in cancer tissues was 69.81% (37/53), which was much higher than the 33.96% (18/53) in adjacent tissues (P < 0.01). The positive expression rate of IGFBP2 in cancer tissues was 62.26% (33/53), which was markedly higher than the 28.30% (15/53) in adjacent tissues (P < 0.01). The proportion of TNM stage III + IV, high Gleason score and PSA > 15 ng/mL was visibly higher in patients with positive expression of YTHDF1 than in patients with negative expression of YTHDF1 (P < 0.05). The proportion of TNM stage III + IV, high Gleason score and PSA > 15 ng/mL in IGFBP2 positive patients was sensibly higher than that in IGFBP2 negative patients (P < 0.05). YTHDF1 positive group had a median survival time of 35 months, which was evidently shorter than 44 months of YTHDF1 negative group (P < 0.05). The IGFBP2 positive group had a median survival time of 32 months, which was clearly shorter than 45 months of IGFBP2 negative group (P < 0.05). In addition, TNM stage, Gleason score, PSA, YTHDF1 and IGFBP2 were independent risk factors for poor prognosis of PC (P < 0.05). CONCLUSIONS: YTHDF1 and IGFBP2 were independent risk factors for poor prognosis of PC patients. They may be involved in the progression of prostate cancer, and serve as potential biomarkers for evaluating the prognosis of patients. However, its clinical translation value needs to be further verified by large sample and multi-center studies.

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