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Phospholipase C epsilon 1 (PLCE1) is a susceptibility gene in esophageal squamous cell carcinoma (ESCC). Nevertheless, the role of PLCE1 in ESCC tumorigenesis has not been elucidated. In this study, we determined the function of PLCE1 and its regulatory microRNA (miRNA) in ESCC. PLCE1 protein was excessively expressed in ESCC and precancerous lesions compared with that in normal tissues. High PLCE1 expression levels in ESCC were significantly linked with poor overall survival. Knockdown of PLCE1 promoted the apoptosis, cytokine-induced apoptosis, and sensitivity of cancer cells to chemotherapeutic drugs but abrogated the proliferation and EMT phenotype of ESCC in vitro. Notably, miR-145 was newly identified as a potent repressor of PLCE1 expression by directly targeting the 3′UTR of PLCE1. MiR-145 also inhibited cell proliferation, migration, and metastasis, as well as controlled the cytoskeleton dynamics of esophageal cancer. Moreover, miR-145 was expressed at low levels in a large cohort of patients with ESCC and was inversely correlated with PLCE1 protein expression in cancer cells and tissues. These findings demonstrate that PLCE1 functions as tumor promoter in ESCC and can be suppressed by miR-145 through inhibition of PLCE1 translation. Hence, delivery of PLCE1-targeting miR-145 is a potential therapeutic approach for esophageal cancer.

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most aggressively malignant tumors with dismal prognosis. Profilin 2 (PFN2) is an actin-binding protein that regulates the dynamics of actin polymerization and plays a key role in cell motility. Recently, PFN2 have emerged as significant regulators of cancer processes. However, the clinical significance and biological function of PFN2 in ESCC remain unclear.MethodsPFN2 protein expression was validated by immunohistochemistry (IHC) on tissue microarray from Chinese Han and Kazakh populations with ESCC. The associations among PFN2 expression, clinicopathological features, and prognosis of ESCC were analyzed. The effects on cell proliferation, invasion and migration were examined using MTT and Transwell assays. Markers of epithelial–mesenchymal transition (EMT) were detected by Western blot analysis.ResultsCompared with normal esophageal epithelium (NEE), PFN2 protein expression was markedly increased in low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and ESCC, increased gradually from LGIN to ESCC, and finally reached high grade in HGIN in the Han population. Similarly, PFN2 protein was more overexpressed in ESCC than in NEE in the Kazakh population. The results of Western blot analysis also showed that PFN2 expression was significantly higher in the ESCC tissue than in a matched adjacent non-cancerous tissue. PFN2 expression was positively correlated with invasion depth and lymph node metastasis. High PFN2 expression was significantly correlated with short overall survival (OS) (P = 0.023). Cox regression analysis revealed that PFN2 expression was an independent prognostic factor for poor OS in ESCC. Downregulation of PFN2 inhibited, rather than proliferated, cell invasion and migration, as well as induced an EMT phenotype, including increased expression of epithelial marker E-cadherin, decreased mesenchymal marker Vimentin, Snail, Slug and ZEB1, and morphological changes in ESCC cells in vitro.ConclusionsOur findings demonstrate that PFN2 has a novel role in promoting ESCC progression and metastasis and portending a poor prognosis, indicating that PFN2 could act as an early biomarker of high-risk population. Targeting PFN2 may offer a promising therapeutic strategy for ESCC treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0884-y) contains supplementary material, which is available to authorized users.

PurposeThis study aimed to compare the potential diagnostic efficacy of gallium68-fibroblast-activation protein inhibitor ([68Ga]Ga-FAPI-04) and fluorine18-fluorodeoxyglucose ([18F]-FDG) positron emission tomography-computed tomography (PET/CT) for primary tumors, lymph nodes, and distant metastatic lesions of gastric cancer (GC), and to explore the effects of [68Ga]Ga-FAPI-04 and [18F]-FDG on tumor staging and restaging in GC.MethodsThis single-center retrospective study (NCT2100044131) was conducted at the Affiliated Hospital of the Southwest Medical University between June 2020 and December 2021. Images of patients with GC who were pathologically confirmed and underwent contemporaneous [18F]-FDG and [68Ga]Ga-FAPI-04 PET/CT within 1 week were analyzed. The diagnostic efficacy of [68Ga]Ga-FAPI-04 PET/CT and [18F]-FDG PET/CT for TNM staging of GC was compared using McNemar test. The maximum standard uptake value (SUVmax) of each lesion in the two imaging types was compared using the Mann-Whitney U test.ResultsIn total, 25 patients with GC (mean age, 56 ± 12 years) were evaluated. [68Ga]Ga-FAPI-04 PET/CT exhibited higher sensitivity compared to [18F]-FDG PET/CT for detecting primary tumors (18/19 [94.74%] vs. 13/19 [68.42%], χ2 = 6.866, P < 0.01), lymph node metastasis (75/77 [97.40%] vs. 32/77 [41.56%], χ2 = 2.888, P =0.089), and distant metastases (275/283 [97.17%] vs. 122/283 [43.11%], χ2 = 11.858, P < 0.01). [68Ga]Ga-FAPI-04 accumulation was significantly higher than that of [18F]FDG in tumors (median SUVmax, 10.28 vs 3.20; U=59.00, P < 0.01), lymph node metastasis metastases (median SUVmax, 9.20 vs 3.15; U=53.50, P < 0.01), and distant metastases (median SUVmax, 8.00 vs 4.20; U=200.00, P < 0.01). Compared to [18F]-FDG PET/CT, [68Ga]Ga-FAPI-04 PET/CT resulted in new oncological findings in 14/25 patients and corrected tumor staging or restaging in 7/25 patients.ConclusionOur preliminary results regarding the impact of [68Ga]Ga-FAPI-04 PET/CT on tumor staging highlight the potential of this approach for increasing the accuracy of GC diagnosis, which may facilitate treatment decision-making.