PLCE1 mRNA and Protein Expression and Survival of Patients with Esophageal Squamous Cell Carcinoma and Gastric Adenocarcinoma

Abstract

Background 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. Methods 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). Results 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). Conclusions 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. Impact A potential role for PLCE1 in the early detection and/or therapy of ESCC and GCA warrants further investigation.

MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5β1/FAK/ERK pathway

“…With the rapid development of highthroughput detection techniques, gene expression data are accumulating rapidly in public repositories and a massive amount of differentially expressed genes (DEGs) between GC and normal tissue has been identified in several studies [5][6][7][8][9] . Many DEGs have been validated as oncogenes or tumor suppressors, which effect different malignant phenotypes of GC including proliferation, angiogenesis, metastasis, and chemoresistance via activating or inactivating multiple downstream signaling pathways [5][6][7][8][9] . But owing to different sample resources, experimental techniques, and bioinformatics algorithms, the results among these studies are greatly divergent, and there is still no widely accepted factor dominating the malignant transformation and progression of GC.…”

Phospholipase C ε‑1 gene polymorphisms and prognosis of esophageal cancer patients from a high‑incidence region in northern China

“…However, it remains controversial whether PLCE1 acts as an oncogene or a tumor suppressor in ESCC development and progression. Hu et al (10) and Li et al (24) reported decreased mRNA in ESCC tumors compared with that in the adjacent normal esophagus, but no difference in protein expression. By contrast, ESCC tissues exhibited a higher PLCE1 protein expression compared with normal tissues in other studies (3,23,(28)(29)(30).…”

“…Specifically, one study reported that high PLCE1 protein expression in ESCC was associated with poor survival (23), while increased tumor/normal-fold change of mRNA and protein expression in ESCC was associated with improved survival in another study (24). To the best of our knowledge, the present study is the first to evaluate the association between the rs2274223 SNP and survival of ESCC patients of Han nationality, and found no correlation, which is similar to the results in the northern Indian population (7).The PLCE1 rs2274223 SNP, a non-synonymous SNP causing an amino acid change from His to Arg in the 26th exon, is located at the calcium-binding domain, indicating its crucial functional significance.…”

“…It was previously demonstrated that PLCE1 was involved in the development and progression of various cancers, including esophageal cancer (3,10,(16)(17)(18)(19)(20)(21)(22). In addition, the expression of PLCE1 was associated with the survival of patients with esophageal cancer (23,24). In fact, identifying applicable biomarkers for ESCC prognosis may be helpful in improving the outcome of ESCC patients.…”

PLCE1 polymorphisms and expression combined with serum AFP level predicts survival of HBV-related hepatocellular carcinoma patients after hepatectomy

“…However, PLCE1 is thought to act as an oncogene in bladder cancer [42, 43], non-small cell lung cancer [44], skin cancer [45], and head and neck cancer [46]. Upregulation of PLCE1 mRNA level is associated with longer survival in gastric cardia adenocarcinoma (GCA) and ESCC, while the transcript is downregulated in GCA and ESCC tumor tissue [47], which was confirmed by another study of ESCC patients [30]. However, higher PLCE1 expression was observed in Chinese Kazakh ESCC patients and ESCC tumor cell lines [48].…”