PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer.
PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer.
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PTEN损失增加了PD-L1蛋白表达，并影响大肠癌中PD-L1表达与临床参数之间的相关性。
DOI：
10.1371/journal.pone.0065821
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Song M;Chen D;Lu B;Wang C;Zhang J;Huang L;Wang X;Timmons CL;Hu J;Liu B;Wu X;Wang L;Wang J;Liu H
程序性死亡配体-1 (PD-L1) 已被确定为与一系列癌症预后不良相关的因素，据报道主要是由神经胶质瘤中 PTEN 缺失引起的。然而，PD-L1 及其 PTEN 调节在结直肠癌 (CRC) 中的临床效果尚未确定。在本研究中，我们验证了PTEN对PD-L1的调节作用，并进一步确定了PTEN对CRC中PD-L1表达与临床参数之间相关性的影响。采用RNA干扰方法下调SW480、SW620和HCT116细胞中PTEN的表达。结果表明，与阴性对照相比，转染 siRNA PTEN 的细胞中 PD-L1 蛋白显着增加，但 mRNA 没有显着增加。此外，PTEN调节PD-L1表达的能力不受PD-L1主要诱导剂IFN-γ的明显影响。使用组织微阵列免疫组织化学检测 404 名 CRC 患者样本中的 PD-L1 和 PTEN。 PD-L1过表达与远处转移（P<0.001）、TNM分期（P<0.01）、转移进展（P<0.01）和PTEN表达（P<0.001）显着相关。单变量分析显示，PD-L1高表达的患者总生存率较差（P<0.001）。然而，多变量分析并不支持PD-L1作为独立的预后因素（P = 0.548）。对 310 名 CRC 患者的单变量（P<0.001）和多变量生存（P<0.001）分析显示，高水平的 PD-L1 表达与转移进展风险增加相关。此外，在 39 名无 PTEN 表达的患者中，PD-L1 对 CRC 的临床效果没有统计学意义（远处转移：P = 0.102；TNM 分期：P = 0.634，总生存期：P = 0.482）。 PD-L1可用于识别转移风险高、预后不良的CRC患者。这种临床表现可能部分与PTEN表达有关。
Programmed death ligand-1 (PD-L1) has been identified as a factor associated with poor prognosis in a range of cancers, and was reported to be mainly induced by PTEN loss in gliomas. However, the clinical effect of PD-L1 and its regulation by PTEN has not yet been determined in colorectal cancer (CRC). In the present study, we verified the regulation of PTEN on PD-L1 and further determined the effect of PTEN on the correlation between PD-L1 expression and clinical parameters in CRC. RNA interference approach was used to down-regulate PTEN expression in SW480, SW620 and HCT116 cells. It was showed that PD-L1 protein, but not mRNA, was significantly increased in cells transfected with siRNA PTEN compared with the negative control. Moreover, the capacity of PTEN to regulate PD-L1 expression was not obviously affected by IFN-γ, the main inducer of PD-L1. Tissue microarray immunohistochemistry was used to detect PD-L1 and PTEN in 404 CRC patient samples. Overexpression of PD-L1 was significantly correlated with distant metastasis (P<0.001), TNM stage (P<0.01), metastatic progression (P<0.01) and PTEN expression (P<0.001). Univariate analysis revealed that patients with high PD-L1 expression had a poor overall survival (P<0.001). However, multivariate analysis did not support PD-L1 as an independent prognostic factor (P = 0.548). Univariate (P<0.001) and multivariate survival (P<0.001) analysis of 310 located CRC patients revealed that high level of PD-L1 expression was associated with increased risks of metastatic progression. Furthermore, the clinical effect of PD-L1 on CRC was not statistically significant in a subset of 39 patients with no PTEN expression (distant metastasis: P = 0.102; TNM stage: P = 0.634, overall survival: P = 0.482). PD-L1 can be used to identify CRC patients with high risk of metastasis and poor prognosis. This clinical manifestation may be partly associated with PTEN expression.
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影响因子：
11.5
作者：
Konishi, J;Yamazaki, K;Nishimura, M
通讯作者：
Nishimura, M
影响因子：
4
作者：
Planchon, Sarah M.;Waite, Kristin A.;Eng, Charis
通讯作者：
Eng, Charis
影响因子：
2.4
作者：
Sawai H;Yasuda A;Ochi N;Ma J;Matsuo Y;Wakasugi T;Takahashi H;Funahashi H;Sato M;Takeyama H
通讯作者：
Takeyama H
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM
影响因子：
11.5
作者：
Nomi, Takeo;Sho, Masayuki;Nakajima, Yoshiyuki
通讯作者：
Nakajima, Yoshiyuki