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Showing papers by "Weiqi Sheng published in 2017"


Journal ArticleDOI
TL;DR: PVT1 may be a valuable prognostic predictor for gastric cancer, and the positive feedback loop of PVT1-FOXM1 could be a therapeutic target in pharmacologic strategies.
Abstract: Purpose: The long, noncoding RNA (lncRNA) PVT1 is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular mechanisms of PVT1 in gastric cancer tumorigenesis and progression.Experimental Design: The expression level of PVT1 was determined by RT-qPCR analysis in 190 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANT). The biologic functions of PVT1 were assessed by in vitro and in vivo functional experiments. RNA protein pull-down assays and LS/MS mass spectrometry analysis were performed to detect and identify the PVT1- interacting protein FOXM1. Protein-RNA immunoprecipitation assays were conducted to examine the interaction of FOXM1 and PVT1 Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of FOXM1 on the PVT1 promoter.Results: The lncRNA PVT1 was significantly upregulated in gastric cancer tissues compared with ANTs. High expression of PVT1 predicted poor prognosis in patients with gastric cancer. PVT1 enhanced gastric cancer cell proliferation and invasion in vitro and in vivoPVT1 directly bound FOXM1 protein and increased FOXM1 posttranslationally. Moreover, PVT1 is also a FOXM1-responsive lncRNA, and FOXM1 directly binds to the PVT1 promoter to activate its transcription. Finally, PVT1 fulfilled its oncogenic functions in a FOXM1-mediated manner.Conclusions: Our study suggests that PVT1 promotes tumor progression by interacting with FOXM1. PVT1 may be a valuable prognostic predictor for gastric cancer, and the positive feedback loop of PVT1-FOXM1 could be a therapeutic target in pharmacologic strategies. Clin Cancer Res; 23(8); 2071-80. ©2016 AACR.

198 citations


Journal ArticleDOI
TL;DR: It is recommended that, except for some selected patients with NF-pNETs <1 cm, incidentally discovered and unacceptable surgical risks, all others with NF’s ≤2 cm should undergo tumor resection with lymph node dissection or at least lymph node sampling and careful postoperative surveillance.
Abstract: The incidence of small (≤2 cm), non-functioning pancreatic neuroendocrine tumors (NF-pNETs) increased in the last decades. Before making appropriate strategy for patients with NF-pNETs ≤2 cm, pathological confirmation is vital. Incidentally diagnosed, sporadic small NF-pNETs may bring aggressive behavior and poor prognosis, such as extrapancreatic extension, lymph nodal metastasis, distant metastasis and recurrence, even causing disease-related death. Understanding and formulating an appropriate strategy for the patients with sporadic small, non-functioning pancreatic neuroendocrine tumors have been controversial for some time. Although several studies have reported that patients with NF-pNETs ≤2 cm had less rate of malignant behavior compared with larger ones (>2 cm); and the surgery approach may leading to surgery-related pancreatic complications; but there is still a lack of level I evidence to convince surgeons to abandon all cases with sporadic small NF-pNETs. Based on an updated literature search and review, the members of the Chinese Study Group for Neuroendocrine Tumors (CSNET) from high-volume centers have reached a consensus on the issue of the management strategy for the sporadic small NF-pNETs. We recommend that, except for some selected patients with NF-pNETs <1 cm, incidentally discovered and unacceptable surgical risks, all others with NF-pNETs ≤2 cm should undergo tumor resection with lymph node dissection or at least lymph node sampling and careful postoperative surveillance.

35 citations


Journal ArticleDOI
TL;DR: It is shown that PTTG3P expression was abnormally up‐regulated in GC tissues compared with that in normal tissues both in cases of clinical samples and the cohort from The Cancer Genome Atlas (TCGA) database, and the pseudogene functioned independently of its parent genes.
Abstract: Pseudogenes play a crucial role in cancer progression. However, the role of pituitary tumour-transforming 3, pseudogene (PTTG3P) in gastric cancer (GC) remains unknown. Here, we showed that PTTG3P expression was abnormally up-regulated in GC tissues compared with that in normal tissues both in our 198 cases of clinical samples and the cohort from The Cancer Genome Atlas (TCGA) database. High PTTG3P expression was correlated with increased tumour size and enhanced tumour invasiveness and served as an independent negative prognostic predictor. Moreover, up-regulation of PTTG3P in GC cells stimulated cell proliferation, migration and invasion both in vitro in cell experiments and in vivo in nude mouse models, and the pseudogene functioned independently of its parent genes. Overall, these results reveal that PTTG3P is a novel prognostic biomarker with independent oncogenic functions in GC.

33 citations


Journal ArticleDOI
TL;DR: A higher dose of weekly irinotecan in combination with capecitabine-based CRT is feasible under the guidance of the UGT1A1∗28 genotype and further clinical trials at these dose levels are warranted.

11 citations


Journal ArticleDOI
TL;DR: Similar RAS mutation, dMMR frequency and lower BRAF mutation was observed in Chinese patients compared to western patients, and a distinct molecular heterogeneity was found between patients with right-sided and left-sided CRCs.
Abstract: // Junjie Peng 1, 2, * , Dan Huang 2, 3, * , Graeme Poston 4 , Xiaoji Ma 1, 2 , Renjie Wang 1, 2 , Weiqi Sheng 2, 3 , Xiaoyan Zhou 2, 3 , Xiaoli Zhu 2, 3 and Sanjun Cai 1, 2 1 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 3 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China 4 Department of Surgery, Aintree University Hospital, Liverpool L9 7AL, UK * These authors have contributed equally to this work Correspondence to: Junjie Peng, email: pengjj@shca.org.cn Keywords: colorectal cancer, RAS, BRAF, mutation, heterogeneity Received: August 31, 2016 Accepted: November 22, 2016 Published: March 14, 2017 ABSTRACT Purpose: To assess the biological variability of clinical meaningful molecular markers and their clinical correlations in Chinese patients with colorectal cancer (CRC). Materials and methods: In this prospective observational study, frequencies and clinico-pathological features of RAS and BRAFV600E mutations, deficiency of DNA mismatch repair (dMMR) were evaluated in patients with colorectal cancer staged I-IV. The molecular heterogeneity between right-sided and left-sided colorectal cancers was studied in our series by classifying patients with different mutations and dMMR status. Results: Among 400 evaluable patients, mutations in KRAS exon 2, exon 3 or 4, NRAS and BRAFV600E were detected in 36%, 7.5%, 3.5% and 2.5%, respectively. RAS mutations were significantly higher in metastatic CRCs (56.4% vs. 43.1%, p=0.015) and right-sided CRCs (62.5% vs 41.7%, p=0.003). In 212 RAS wild-type patients, V600E mutation was higher in older patients (9.5% vs. 2.2%, p=0.017), women (9.2% vs. 2.2%, p=0.021) and right-sided CRCs (10.5% vs. 3.4%, p=0.06). dMMR was detected in 7.75% of all stages of CRCs, with the highest dMMR rate of 40% in stage II right-sided colon cancer. Conclusions: By assessing the mutations and clinical correlations of RAS and BRAF genes, and dMMR status, similar RAS mutation, dMMR frequency and lower BRAF mutation was observed in Chinese patients compared to western patients. A distinct molecular heterogeneity was found between patients with right-sided and left-sided CRCs.

8 citations


Journal ArticleDOI
Shujuan Ni1, Junjie Peng1, Dan Huang1, Midie Xu1, Lei Wang1, Cong Tan1, Hui Sun1, Sanjun Cai1, Weiqi Sheng1 
TL;DR: This work has shown that human epidermal growth factor receptor 2 (HER2) overexpression or amplification may be a potentially predictive factor for anti-HER2 response and an...
Abstract: e15099Background: Recent studies have shown that human epidermal growth factor receptor 2 (HER2) overexpression or amplification may be a potentially predictive factor for anti-HER2 response and an...

7 citations