Genetic variation in PLCE1 is associated with gastric cancer survival in a Chinese population

Luo, Dewei; Gao, Yan; Wang, Shizhi; Wang, Meilin; Wu, Dongmei; Wang, Wei; Xu, Ming; Zhou, Jianwei; Gong, Weida; Tan, Yongfei; Zhang, Zhengdong

doi:10.1007/s00535-011-0445-3

Cited by 37 publications

(29 citation statements)

References 30 publications

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“…1). This is consistent with other studies2324. Further stratified analysis on pathological features showed that many factors, including histological type, tumor differentiation, depth of invasion, lymph node metastasis and TNM stages of patients, strongly influenced the survival of GC patients carrying MTRR 66GA + GG genotypes (Table 3).…”

Section: Discussionsupporting

confidence: 91%

The effects of genomic polymorphisms in one-carbon metabolism pathways on survival of gastric cancer patients received fluorouracil-based adjuvant therapy

Zhao

et al. 2016

Sci Rep

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5-fluorouracil (5-FU) is widely used to treat patients with gastric cancer (GC). However, the response rate is quite heterogeneous. The single nucleotide polymorphisms (SNPs) and their interactions of genes in the one-carbon metabolism (OCM) pathway, including Methylenetetrahydrofolate reductase (MTHFR), Methionine synthase reductase (MTRR), Methionine synthase (MTR), and Thymidylate synthase (TS), significantly affect 5-FU metabolism. In this study, 650 stage II-III patients were recruited from 1998 to 2006. Among them, 251 received 5-FU treatment and other 399 patients were untreated. The Cox regression analysis, log-rank tests and Kaplan–Meier plots were adopted. In the chemotherapy cohort, MTRR 66 GA + GG genotypes decreased death risk, however, the protect effect of MTRR 66 GA + GG disappeared when GC patients simultaneously had MTHFR 677TT + TC or MTR 2756GG + GA genotypes. TS 5′-UTR 2R3R + 3R3R genotypes also prolonged overall survival of patients treated with 5-FU. And this favorable prognosis obviously enhanced when GC patients simultaneously had TS 3′-UTR DD + DI and TS 5′-UTR 2R3R + 3R3R genotypes. Our findings showed that the polymorphisms of MTRR 66 A > G and TS 5′-UTR 3R > 2R may be potential prognostic factors for GC patients receiving 5-FU.

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Section: Discussionsupporting

confidence: 91%

The effects of genomic polymorphisms in one-carbon metabolism pathways on survival of gastric cancer patients received fluorouracil-based adjuvant therapy

Zhao

et al. 2016

Sci Rep

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“…Also two replicated independent studies have also validated the association of PLCE1 rs2274223A>G polymorphism with head and neck cancer and gastric cancer in Chinese population (Luo et al, 2011;Ma et al, 2011). Recently, a metaanalysis of PLCE1 rs2274223 A>G polymorphism also suggested its involvement in conferring increased risk of esophageal cancer risk (Umar et al, 2013).…”

Section: Discussionmentioning

confidence: 97%

Phospholipase C Epsilon 1 (PLCE1 rs2274223A>G, rs3765524C>T and rs7922612C>T) Polymorphisms and Esophageal Cancer Risk in the Kashmir Valley

Malik

Umar

Gupta

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Phospholipase C epsilon 1 (PLCE1) encodes a member of the phospholipase family of proteins that play crucial roles in carcinogenesis and progression of several cancers including esophageal cancer (EC). In two large scale genome-wide association studies (GWAS) single nucleotide polymorphisms (SNP, rs2274223A>G, rs3765524C>T) in PLCE1 were identified as novel susceptibility loci of esophageal cancer (EC) in China.

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“…PLCE1 showed significantly higher expression in esophageal carcinoma tissue. Some studies found that PLCE1 is correlated with the occurrence and development of gastric carcinoma (Luo et al, 2011), colorectal carcinoma (Danielsen et al, 2011), small intestine cancer (Li et al, 2009), head and neck squamous cell carcinoma (Bourguignon et al, 2006) and skin cancer (Bai et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Effects of PLCE1 Gene Silencing by RNA Interference on Cell Cycling and Apoptosis in Esophageal Carcinoma Cells

Zhao¹,

Wei²,

Yang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Esophageal squamous cell carcinoma (ESCC) is one of the most malignancies with a poor prognosis. The phospholipase Cε gene (PLCE1) encodes a novel ras-related protein effector mediating the effects of R-Ras on the actin cytoskeleton and membrane protrusion. However, molecular mechanisms pertinent to ESCC are unclear. We therefore designed PLCE1-special small interfering RNA and transfected to esophageal squamous cell (EC) 9706 cells to investigat the effects of PLCE1 gene silencing on the cell cycle and apoptosis of ESCC and indicate its important role in the development of ESCC. Esophageal cancer tissue specimens and normal esophageal mucosa were obtained and assayed by immunohistochemical staining to confirm overexpression of PLCE1 in neoplasias. Fluorescence microscopy was used to examine transfection efficiency, while the result of PLCE1 silencing was examined by reverse transcription (RT-PCR). Flow cytometry and annexin V apoptosis assays were used to assess the cell cycle and apoptosis, respectively. Expression of cyclin D1 and caspase-3 was detected by Western-blotting. The level of PLCE1 protein in esophageal cancer tissue was significantly higher than that in normal tissue. After transfection, the expression of PLCE1 mRNA in EC 9706 was significantly reduced, compared with the control group. Furthermore, flow cytometry results suggested that the PLCE1 gene silencing arrested the cell cycle in the G0/G1 phase; apoptosis was significantly higher than in the negative control group and mock group. PLCE1 gene silencing by RNAi resulted in decreased expression of cyclin D1 and increased expression of caspase-3. Our study suggests that PLCE1 may be an oncogene and play an important role in esophageal carcinogenesis through regulating proteins which control cell cycling and apoptosis.

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Genetic variation in PLCE1 is associated with gastric cancer survival in a Chinese population

Cited by 37 publications

References 30 publications

The effects of genomic polymorphisms in one-carbon metabolism pathways on survival of gastric cancer patients received fluorouracil-based adjuvant therapy

The effects of genomic polymorphisms in one-carbon metabolism pathways on survival of gastric cancer patients received fluorouracil-based adjuvant therapy

Phospholipase C Epsilon 1 (PLCE1 rs2274223A>G, rs3765524C>T and rs7922612C>T) Polymorphisms and Esophageal Cancer Risk in the Kashmir Valley

Effects of PLCE1 Gene Silencing by RNA Interference on Cell Cycling and Apoptosis in Esophageal Carcinoma Cells

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