P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer.
P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer.
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膀胱癌是最常见的恶性肿瘤之一。晚期癌症的预后尤其差。需要新的预后标记物来指导治疗决策，并促进新的治疗策略的发展，以提高当前治疗方案的成功率。肿瘤微环境的特点是细胞外三磷酸腺苷水平升高。识别ATP的P2X受体与多种恶性肿瘤的生长和转移密切相关。在这里，我们分析了不同的P2X受体亚型作为肌肉浸润性膀胱癌预后标志物的潜力。体外实验证实细胞外ATP和P2X受体对膀胱癌细胞具有促生长作用。与此一致的是，我们对173例患者的癌组织样本的分析表明，P2X1和P2X7受体的表达是一个独立的负面预测因素，是肌肉浸润性膀胱癌的潜在治疗靶点。膀胱癌是全球最常见的癌症死亡原因之一。肌肉浸润性膀胱癌(MIBC)预后特别差。在一些恶性肿瘤中，嘌呤能P2X受体(P2XRs)的过度表达与不良预后有关。在此，我们研究了P2XR在膀胱癌细胞体外增殖中的作用以及在MIBC患者中表达的预后价值。用T24、RT4和未转化的TRT-HU-1细胞进行的细胞培养实验表明，膀胱细胞系细胞培养上清液中的高ATP浓度与更高的恶性程度之间存在联系。此外，高度恶性的T24膀胱癌细胞的增殖依赖于通过P2X受体的自分泌信号。应用免疫组织化学方法检测173例MIBC患者肿瘤标本中P2X1R、P2X4R和P2X7R的表达。高表达的P2X1R与疾病进展和生存时间缩短的病理参数相关。在多因素分析中，P2X1R和P2X7R的高联合表达增加了远处转移的风险，是总体和肿瘤特异性生存的独立负面预测因素。我们的结果表明，P2X1R/P2X7R表达评分是MIBC患者强有力的阴性预后标志物，而P2XR介导的通路是膀胱癌新的治疗策略的潜在靶点。
Bladder cancer is one of the most common malignancies. The prognosis is particularly poor for advanced cancer. There is a need for new prognostic markers to guide treatment decisions and promote the development of novel therapeutic strategies to increase the success rate of current treatment regimens. The tumor microenvironment is characterized by an increase in extracellular ATP levels. ATP-recognizing P2X receptors have been implicated in the growth and metastasis of various malignant cancers. Here, we analyzed the potential of different P2X receptor subtypes as prognostic markers in muscle-invasive bladder cancer. In vitro experiments confirmed a growth-promoting effect of extracellular ATP and P2X receptors on bladder cancer cells. In agreement, our analyses of cancer tissue samples from 173 patients showed that expression of P2X1 and P2X7 receptors is an independent negative predictor of survival and a potential therapeutic target in muscle-invasive bladder cancer. Bladder cancer is amongst the most common causes of cancer death worldwide. Muscle-invasive bladder cancer (MIBC) bears a particularly poor prognosis. Overexpression of purinergic P2X receptors (P2XRs) has been associated with worse outcome in several malignant tumors. Here, we investigated the role of P2XRs in bladder cancer cell proliferation in vitro and the prognostic value of P2XR expression in MIBC patients. Cell culture experiments with T24, RT4, and non-transformed TRT-HU-1 cells revealed a link between high ATP concentrations in the cell culture supernatants of bladder cell lines and a higher grade of malignancy. Furthermore, proliferation of highly malignant T24 bladder cancer cells depended on autocrine signaling through P2X receptors. P2X1R, P2X4R, and P2X7R expression was immunohistochemically analyzed in tumor specimens from 173 patients with MIBC. High P2X1R expression was associated with pathological parameters of disease progression and reduced survival time. High combined expression of P2X1R and P2X7R increased the risk of distant metastasis and was an independent negative predictor of overall and tumor-specific survival in multivariate analyses. Our results suggest that P2X1R/P2X7R expression scores are powerful negative prognostic markers in MIBC patients and that P2XR-mediated pathways are potential targets for novel therapeutic strategies in bladder cancer.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
--
作者：
Amoroso F;Salaro E;Falzoni S;Chiozzi P;Giuliani AL;Cavallesco G;Maniscalco P;Puozzo A;Bononi I;Martini F;Tognon M;Di Virgilio F
通讯作者：
Di Virgilio F
影响因子：
3.5
作者：
Burnstock G;Knight GE
通讯作者：
Knight GE
影响因子：
2.9
作者：
Boldrini L;Giordano M;Alì G;Melfi F;Romano G;Lucchi M;Fontanini G
通讯作者：
Fontanini G
影响因子：
2.9
作者：
Choi, Ji Hun;Ji, Young Geon;Lee, Dong Hyeon
通讯作者：
Lee, Dong Hyeon