PLCE1 mRNA and protein expression and survival of patients with esophageal squamous cell carcinoma and gastric adenocarcinoma.

PLCE1 mRNA and protein expression and survival of patients with esophageal squamous cell carcinoma and gastric adenocarcinoma.
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DOI:
10.1158/1055-9965.epi-13-1329
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发表时间:
2014-08
期刊:
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子:
--
通讯作者:
Taylor PR
Taylor PR
中科院分区:
其他
文献类型:
--
作者:
Li WQ;Hu N;Burton VH;Yang HH;Su H;Conway CM;Wang L;Wang C;Ding T;Xu Y;Giffen C;Abnet CC;Goldstein AM;Hewitt SM;Taylor PR

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PLCE1 (10q23)的种系遗传变异与中国人食管鳞状细胞癌(ESCC)和胃癌的风险一致相关。我们评估了PLCE1 mRNA和蛋白在配对肿瘤-正常组织中的表达,以及它们与生存的关系。应用Affymetrix基因芯片U133对ESCC (n=132)、胃贲门腺癌(n= 62)和胃非贲门腺癌(n= 72)配对的肿瘤-正常组织进行PLCE1 mRNA的检测。我们利用免疫组化技术检测了ESCC (n=303)、GCA (n=298)和GNCA (n=124)配对肿瘤-正常组织组织微阵列切片上PLCE1蛋白的表达。与正常组织相比,PLCE1 mRNA在ESCC肿瘤中表达显著降低(P=0.03, probe_205112_at),在GCA和GNCA肿瘤中表达显著降低(各探针P<0.0001)。ESCC肿瘤中蛋白表达无显著降低(P=0.51)。增加的肿瘤-正常mRNA折叠变化(probe_205112_at)与ESCC患者更长的生存期相关(最高四分位数vs最低四分位数9.6个月;p趋势=0.02)。增加的mRNA肿瘤-正常折叠变化(probe_205111_at)与GCA患者的生存时间延长相关(最高四分位数为10.7个月;P趋势=0.04),但与GNCA患者无关(P=0.72)。与mRNA类似,ESCC中升高的肿瘤-正常蛋白折叠变化也与生存率提高相关(最高四分位数为8.1个月;p趋势=0.04)。在ESCC(仅一个探针)和GCA肿瘤中均观察到PLCE1 mRNA表达异常,并且PLCE1表达的改变似乎与癌症预后有关。PLCE1在ESCC和GCA的早期发现和/或治疗中的潜在作用值得进一步研究。
Germline genetic variants in PLCE1 (10q23) have demonstrated consistent associations with risk of esophageal squamous cell carcinoma (ESCC) and gastric cancer among Chinese. We evaluated PLCE1 mRNA and protein expression in paired tumor-normal tissues, and their relationship with survival. PLCE1 mRNA was profiled using three probes in the Affymetrix GeneChip U133 for paired tumor-normal tissues of ESCC (n=132), gastric cardia adenocarcinoma (GCA, n=62) and gastric noncardia adenocarcinoma (GNCA, n=72). We used immunohistochemistry to detect PLCE1 protein on slides from tissue microarrays in paired tumor-normal tissues of ESCC (n=303), and tumors of GCA (n=298) and GNCA (n=124). Compared with normal tissues, PLCE1 mRNA expression was significantly reduced in ESCC tumors (P=0.03, probe_205112_at), as well as in GCA and GNCA tumors (P<0.0001, each probe). Protein expression was non-significantly reduced in ESCC tumors (P=0.51). Increased tumor-normal mRNA fold change (probe_205112_at) was associated with longer survival in ESCC (9.6 months for highest vs lowest quartile; P-trend=0.02). Increased mRNA tumor-normal fold change (probe_205111_at) was associated with longer survival for GCA (10.7 months for highest quartile; P-trend=0.04), but not for GNCA cases (P=0.72). Similar to mRNA, elevated tumor-normal fold change for protein in ESCC was also associated with improved survival (8.1 months for highest quartile; P-trend=0.04). Dysregulated PLCE1 mRNA expression was observed for both ESCC (one probe only) and GCA tumors, and the altered PLCE1 expression appears to be associated with cancer prognosis. A potential role for PLCE1 in the early detection and/or therapy of ESCC and GCA warrants further investigation.