Vacuolar Membrane ATPase Activity 21 Predicts a Favorable Outcome and Acts as a Suppressor in Colorectal Cancer.
Vacuolar Membrane ATPase Activity 21 Predicts a Favorable Outcome and Acts as a Suppressor in Colorectal Cancer.
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DOI：
10.3389/fonc.2020.605801
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发表时间：
2020
影响因子：
4.7
通讯作者：
Xie Z
中科院分区：
文献类型：
--
作者：
Zhang F;Shen H;Fu Y;Yu G;Cao F;Chang W;Xie Z
细胞外和/或细胞内对肿瘤细胞内pH的调控在肿瘤治疗中可能具有显著的潜力。虽然V-ATPase复合体V0结构域的组装因子基因是维持细胞内pH稳态所必需的，但它们在结直肠癌(CRC)中的意义仍然很大程度上是未知的。在这里，我们使用生物信息学从已知的V0结构域的组装因子基因中识别候选基因，并通过免疫组织化学(IHC)对661名患者的结直肠癌和邻近正常标本进行进一步评估。采用单因素和多因素COX分析评估影响预后的因素。体外和体内研究VMA21基因表达变化对肿瘤生长的影响。在五个已知的组装因子中，只有VMA21在mRNA和蛋白水平上在结直肠癌和邻近正常组织中显示出差异表达。VMA21高表达患者具有较高的分化程度和较长的疾病特异性生存期(DSS)。Vma21在肿瘤中的高表达也是DSS的独立预测因素(危险比，0.345；95%可信区间，0.123-0.976)，协变量包括TNM分期和分化程度。VMA21过表达降低了结直肠癌的生长，而VMA21基因敲除则促进了体外和体内的结直肠癌生长。在I-III期疾病患者中，VMA21的表达抑制了CRC的生长，并预测了有利的DSS。
Extracellular and/or intracellular manipulation of pH in tumor may have noticeable potential in cancer treatment. Although the assembly factor genes of V0 domain of the V-ATPase complex are required for intracellular pH homeostasis, their significance in colorectal cancer (CRC) remains largely unknown. Here, we used bioinformatics to identify the candidates from known assembly factor genes of the V0 domain, which were further evaluated by immunohistochemistry (IHC) in CRC and adjacent normal specimens from 661 patients. Univariate and multivariate Cox analyses were used to evaluate factors contributing to prognosis. The effects of variations in the expression of VMA21 on tumor growth were assessed in vitro and in vivo. Of five known assembly factors, only VMA21 showed differential expression between CRC and adjacent normal tissues at both mRNA and protein levels. Patients with high VMA21 expression had higher differentiation grade and longer disease-specific survival (DSS) at stages I–III disease. High VMA21 expression in tumors was also an independent predictor of DSS (hazard ratio, 0.345; 95% confidence interval, 0.123–0.976), with covariates included TNM stage and differentiation grade. VMA21 overexpression decreased CRC growth, whereas VMA21 knockdown increased CRC growth in vitro and in vivo. VMA21 expression suppresses CRC growth and predicts a favorable DSS in patients with stage I-III disease.
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DOI：
10.1084/jem.20170453
发表时间：
2017-12-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Rujano MA;Cannata Serio M;Panasyuk G;Péanne R;Reunert J;Rymen D;Hauser V;Park JH;Freisinger P;Souche E;Guida MC;Maier EM;Wada Y;Jäger S;Krogan NJ;Kretz O;Nobre S;Garcia P;Quelhas D;Bird TD;Raskind WH;Schwake M;Duvet S;Foulquier F;Matthijs G;Marquardt T;Simons M
通讯作者：
Simons M
GEPIA：用于癌症和正常基因表达谱和交互式分析的网络服务器。
影响因子：
14.9
作者：
Tang Z;Li C;Kang B;Gao G;Li C;Zhang Z
通讯作者：
Zhang Z
影响因子：
13.5
作者：
Cannata Serio, Magda;Graham, Laurie A.;Lefeber, Dirk J.
通讯作者：
Lefeber, Dirk J.
影响因子：
4
作者：
Xue, Min;Tao, Weimin;Gao, Xiwen
通讯作者：
Gao, Xiwen
影响因子：
16.6
作者：
Pareja, Fresia;Brandes, Alissa H.;Reis-Filho, Jorge S.
通讯作者：
Reis-Filho, Jorge S.