The clinical and biological significance of STAT1 in esophageal squamous cell carcinoma.
The clinical and biological significance of STAT1 in esophageal squamous cell carcinoma.
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STAT1在食管鳞癌中的临床及生物学意义
DOI：
10.1186/1471-2407-14-791
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发表时间：
2014-10-29
期刊：
影响因子：
3.8
通讯作者：
Lai R
中科院分区：
文献类型：
--
作者：
Zhang Y;Molavi O;Su M;Lai R
背景 STAT1（信号转导子和转录激活子 1）的缺失与多种癌症类型的病理学有关。尽管如此，STAT1在食管鳞状细胞癌（ESCC）中的生物学和临床意义尚未得到全面研究。方法使用免疫组织化学方法，我们检测了一组ESCC患者中STAT1的表达；体外实验，我们使用强制基因转染STAT1C到两个STAT1弱/阴性ESCC细胞系中，并在两个STAT1强ESCC细胞系中siRNA敲低STAT1来检测STAT1在ESCC中的功能。结果我们发现STAT1在ESCC中的表达存在异质性，强阳性病例64例（49.0%），弱阳性病例59例（45.0%），阴性病例8例（6.1%）。 STAT1表达与肿瘤侵袭深度和肿瘤大小呈负相关（分别为p=0.047和p=0.029，卡方）。此外，与 STAT1 阴性肿瘤患者相比，STAT1 强/弱肿瘤患者的生存期显着更长（33.6 个月 vs 13.1 个月，p=0.019）。在携带侵袭性细胞学肿瘤的患者 (n=50) 中，STAT1 强肿瘤患者的生存期明显长于 STAT1 弱/阴性肿瘤患者（34.6 个月 vs 20.5 个月，p=0.011）。我们的体外实验表明 STAT1 具有促凋亡作用，并能抑制细胞周期进程和集落形成。最后，我们发现有证据表明，ESCC 细胞中的 STAT1 信号传导下调了 NF-κB 和 STAT3 的表达和/或活性，已知这两者都具有致癌潜力。结论总而言之，我们的研究结果表明 STAT1 是 ESCC 中的肿瘤抑制因子。 ESCC 中常见的 STAT1 缺失导致了这些肿瘤的发病机制。
BackgroundLoss of STAT1 (Signal Transducer and Activator of Transcription-1) has been implicated in the pathobiology of a number of cancer types. Nonetheless, the biological and clinical significance of STAT1 in esophageal squamous cell carcinomas (ESCC) has not been comprehensively studied.MethodsUsing immunohistochemistry, we detected the STAT1 expression in a cohort of ESCC patients;In-vitroexperiments, we used enforced gene transfection ofSTAT1Cinto two STAT1- weak/negative ESCC cell lines and siRNA knockdown of STAT1 in two STAT1-strong ESCC cell lines to detect STAT1 function in ESCC.ResultsWe found that the expression of STAT1 was heterogeneous in ESCC, with 64 (49.0%) strongly positive cases, 59 (45.0%) weakly positive cases and 8 (6.1%) negative cases. STAT1 expression inversely correlated with the depth of tumor invasion and tumor size (p=0.047 and p=0.029, respectively, Chi square). Furthermore, patients with STAT1-strong/weak tumors had a significantly longer survival compared to those with STAT1-negative tumors (33.6 months versus 13.1 months, p=0.019). In patients carrying tumors of aggressive cytology (n=50), those with STAT1-strong tumors survived significantly longer than those with STAT1-weak/negative tumors (34.6 months versus 20.5 months, p=0.011). Ourin-vitroexperiments revealed that STAT1 is proapoptotic and inhibitory to cell-cycle progression and colony formation. Lastly, we found evidence that STAT1 signaling in ESCC cells down-regulated the expression and/or activity of NF-κB and STAT3, both of which are known to have oncogenic potential.ConclusionTo conclude, our findings suggest that STAT1 is a tumor suppressor in ESCC. Loss of STAT1, which is frequent in ESCC, contributes to the pathogenesis of these tumors.
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影响因子：
4.4
作者：
Lee, CK;Smith, E;Levy, DE
通讯作者：
Levy, DE
DOI：
10.1073/pnas.122236099
发表时间：
2002-06-11
影响因子：
11.1
作者：
Costa-Pereira, AP;Tininini, S;Poli, V
通讯作者：
Poli, V
影响因子：
3.7
作者：
Kaganoi, Junichi;Watanabe, Go;Sakai, Yoshiharu
通讯作者：
Sakai, Yoshiharu
影响因子：
4.8
作者：
Kiernan, R;Brès, V;Benkirane, M
通讯作者：
Benkirane, M
STAT1与Survivin在胃癌中的拮抗作用及其临床意义
影响因子：
2.9
作者：
Deng, Hao;Zhen, Hongyan;Liu, Lijiang
通讯作者：
Liu, Lijiang