Li Wen-Qing, Hu Nan, Burton Victoria H, Yang Howard H, Su Hua, Conway Catherine M, Wang Lemin, Wang Chaoyu, Ding Ti, Xu Yi, Giffen Carol, Abnet Christian C, Goldstein Alisa M, Hewitt Stephen M, Taylor Philip R
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD 20852.
Office of the Director, Center for Cancer Research, NCI, Bethesda, MD.
Cancer Epidemiol Biomarkers Prev. 2014 Aug;23(8):1579-1588. doi: 10.1158/1055-9965.EPI-13-1329. Epub 2014 May 27.
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 nonsignificantly 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; Ptrend = 0.02). Increased mRNA tumor-normal fold change (probe_205111_at) was associated with longer survival for GCA (10.7 months for highest quartile; Ptrend = 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; Ptrend = 0.04).
Dysregulated PLCE1 mRNA expression was observed for both ESCC (one probe only) and GCA tumors, and the altered PLCE1 expression seems 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.
在中国人群中,PLCE1(10q23)的种系基因变异已被证明与食管鳞状细胞癌(ESCC)和胃癌的风险存在一致的关联。我们评估了PLCE1 mRNA和蛋白在肿瘤与配对正常组织中的表达情况,以及它们与生存的关系。
使用Affymetrix GeneChip U133中的三种探针检测ESCC(n = 132)、贲门腺癌(GCA,n = 62)和非贲门腺癌(GNCA,n = 72)配对肿瘤与正常组织中的PLCE1 mRNA。我们使用免疫组织化学方法检测ESCC(n = 303)、GCA肿瘤(n = 298)和GNCA肿瘤(n = 124)配对肿瘤与正常组织的组织芯片玻片上的PLCE1蛋白。
与正常组织相比,ESCC肿瘤中PLCE1 mRNA表达显著降低(P = 0.03,探针_205112_at),GCA和GNCA肿瘤中也降低(每个探针P < 0.0001)。ESCC肿瘤中蛋白表达降低不显著(P = 0.51)。ESCC中肿瘤与正常组织mRNA倍数变化增加(探针_205112_at)与更长生存期相关(最高四分位数与最低四分位数相比为9.6个月;Ptrend = 0.02)。GCA中mRNA肿瘤与正常组织倍数变化增加(探针_205111_at)与更长生存期相关(最高四分位数为10.7个月;Ptrend = 0.04),但GNCA病例中无此关联(P = 0.72)。与mRNA相似,ESCC中蛋白肿瘤与正常组织倍数变化升高也与生存期改善相关(最高四分位数为8.1个月;Ptrend = 0.04)。
在ESCC(仅一个探针)和GCA肿瘤中均观察到PLCE1 mRNA表达失调,且PLCE1表达改变似乎与癌症预后相关。
PLCE1在ESCC和GCA的早期检测和/或治疗中的潜在作用值得进一步研究。