Sushi Domain Containing 2 功能障碍导致膀胱癌患者的癌症进展。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
ACS Applied Electronic Materials Pub Date : 2024-08-13 eCollection Date: 2024-01-01 DOI:10.7150/jca.97537
Wei-Ting Kuo, Yi-Chen Lee, Yi-Fang Yang, Ching-Feng Cheng, Ching-Jiunn Tseng, Kuo-Wang Tsai
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引用次数: 0

摘要

膀胱癌是台湾发病率最高的癌症,因此,提高早期肿瘤生物标志物的诊断灵敏度和确定治疗靶点以提高患者生存率至关重要。虽然在多种类型的人类癌症中发现了 SUSD2(Sushi Domain Containing 2)功能障碍,但其在膀胱癌中的生物学作用仍不清楚。癌症基因组图谱分析显示,膀胱癌组织中 SUSD2 mRNA 的表达明显高于邻近的正常组织。SUSD2 表达的升高与病理分期(p = 0.029)、pN 分期(p < 0.001)和 pM 分期(p = 0.047)显著相关。单变量分析显示,SUSD2的高表达与总生存率下降有关(粗危险比=1.70,95%置信区间=1.13-2.56,p=0.01)。多变量分析显示,SUSD2高表达与不良生存结果之间存在显著相关性(调整后危险比=1.53,95%置信区间=1.01-2.31,P=0.043)。IHC分析显示,SUSD2蛋白水平升高与不利病理分期之间存在显著相关性(p < 0.001)。抑制 SUSD2 能明显减少膀胱癌细胞的增殖、集落形成和侵袭。此外,细胞周期分析表明,SUSD2敲除可诱导膀胱癌细胞G2/M期停滞。肿瘤免疫估算资源分析表明,SUSD2的表达与膀胱癌中巨噬细胞浸润和M2巨噬细胞极化显著相关。此外,miR-383-5p直接靶向SUSD2的3'UTR,其异位表达可抑制膀胱癌细胞的生长和运动。我们的研究发现,miR-383-5p/SUSD2轴功能障碍可能会影响细胞生长、转移和肿瘤微环境,从而导致膀胱癌预后不良。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sushi Domain Containing 2 Dysfunction Contributes to Cancer Progression in Patients with Bladder Cancer.

Bladder cancer is the most prevalent type of cancer in Taiwan, and therefore, enhancing the diagnostic sensitivity of biomarkers for early-stage tumors and identifying therapeutic targets to improve patient survival rates are essential. Although Sushi Domain Containing 2 (SUSD2) dysfunction has been identified in several types of human cancer, its biological role in bladder cancer remains unclear. Analysis of The Cancer Genome Atlas revealed significantly higher expression of SUSD2 mRNA in bladder cancer tissues than in adjacent normal tissues. This elevated expression of SUSD2 significantly correlated with pathological stage (p = 0.029), pN stage (p < 0.001), and pM stage (p = 0.047). Univariate analysis revealed that high SUSD2 expression was associated with decreased overall survival (crude hazard ratio = 1.70, 95% confidence interval = 1.13-2.56, p = 0.01). Multivariate analysis revealed a significant correlation between high SUSD2 expression and poor survival outcomes (adjusted hazard ratio = 1.53, 95% confidence interval = 1.01-2.31, p = 0.043). IHC analysis revealed a significant correlation between elevated SUSD2 protein levels and unfavorable pathological stages (p < 0.001). SUSD2 suppression significantly reduced the proliferation, colony formation, and invasion of bladder cancer cells. In addition, cell cycle analysis revealed that SUSD2 knockdown induced G2/M phase arrestin bladder cancer cells. Tumor Immune Estimation Resource analysis indicated that expression of SUSD2 was significantly associated with macrophage infiltration and M2 macrophage polarization in bladder cancer. In addition, miR-383-5p directly targeted the 3'UTR of SUSD2, with its ectopic expression inhibiting the growth and motility of bladder cancer cells. Our study revealed that miR-383-5p/SUSD2 axis dysfunction may contribute to a poor prognosis for bladder cancer by affecting cell growth, metastasis, and the tumor microenvironment.

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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
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