Yuqi He

Performance of a second‐generation methylated SEPT9 test in detecting colorectal neoplasm

Screening and early detection reduces mortality due to colorectal cancer (CRC). Methylated Septin 9 (SEPT9) is a new blood‐based biomarker for CRC. We evaluated the performance of the second‐generation SEPT9 assay for the detection of colorectal neoplasm, and compared it with fecal immunochemical test (FIT).

MicroRNA-185 regulates chemotherapeutic sensitivity in gastric cancer by targeting apoptosis repressor with caspase recruitment domain

Gastric cancer remains the second leading cause of cancer deaths worldwide. Resistance to chemotherapy is a significant barrier for effective cancer treatment. Here, we identified miR-185 to be a contributor to chemosensitivity in gastric cancer. We observed low levels of miR-185 in gastric cancer cell lines and clinical tissues, compared with gastric epithelium cell line and noncancerous tissues. Furthermore, enforced expression of miR-185 increased the sensitivity of gastric cancer cells to low-dose chemotherapeutic agents, which alone cannot trigger significant apoptosis. Conversely, knockdown of endogenous miR-185 prevented high-dose chemotherapy-induced apoptosis. In elucidating the molecular mechanism by which miR-185 participated in the regulation of chemosensitivity in gastric cancer, we discovered that apoptosis repressor with caspase recruitment domain (ARC) is a direct target of miR-185. The role of miR-185 was confirmed in gastric tumor xenograft model. The growth of established tumors was suppressed by a combination therapy using enforced miR-185 expression and a low dose of anticancer drugs. Finally, we found that RUNX3 (Runt-related transcription factor) was involved in the activation of miR-185 at the transcriptional level. Taken together, our results reveal that RUNX3, miR-185 and ARC regulate the sensitivity of gastric cancer cells to chemotherapy.

Factors for Endoscopic Submucosal Dissection in Early Colorectal Neoplasms: A Single Center Clinical Experience in China

Background/Aims Early colorectal (CR) neoplasm can be cured by endoscopic submucosal dissection (ESD), but clinical experience and factors associated with complications from ESD for CR neoplasms in China have not been reported. Methods Seventy-eight cases of early CR neoplasm treated with endoscopic resection performed between December 2012 and December 2013 at Beijing Military General Hospital were included. Factors associated with ESD complications and procedure times were evaluated. Results The en bloc resection rate was 88.5% (69/78), tumor size was 32.1±10.7 mm, and procedure time was 71.8±49.5 minutes. The major complication was perforation, which occurred in 8.97% of the ESD procedures. Multivariate logistic regression analysis indicated that only tumor size (p=0.022) was associated with ESD perforation. Tumor size (p<0.001) and the non-lifting sign (p=0.017) were independent factors for procedure time, and procedure time (p=0.016) was a key factor for en bloc resection. After a median 10 months (range, 4 to 16) of follow-up, no patients had local recurrence. Conclusions This study indicated that ESD is an applicable method for large early CR neoplasm in the colon and rectum. Tumor size and the non-lifting sign might be considerable factors for increased complication rate and procedural time of ESD.

Long noncoding RNA gastric cancer-related lncRNA1 mediates gastric malignancy through miRNA-885-3p and cyclin-dependent kinase 4

Gastric cancer (GC) is one of the most common malignancy and the third leading cancer-related death in China. Long noncoding RNAs (lncRNAs) have been implicated in numerous tumors, including GC, however, the mechanism of many functional lncRNAs is still unclear. In this study, we identified the abundantly expressed lncRNA, RP11-290F20.3, in GC cells and patient tumor tissues. We named this lncRNA as GC-related lncRNA1 (GCRL1), which could regulate gastric cell proliferation and metastasis, both in vitro and in vivo. Mechanistically, miRNA-885-3p (miR-885-3p) could inhibit the cell proliferation and metastasis in GC by negatively regulating the expression of cyclin-dependent kinase 4 (CDK4) at the post-transcriptional level. Further, GCRL1 promoted the cell proliferation and metastasis by sponging miR-885-3p and hence, positively regulating CDK4 in GC cells. Taken together, our results demonstrate a novel regulatory axis of malignant cell proliferation and invasion in GC, comprising GCRL1, miR-885-3p, and CDK4, which may serve as a potential therapeutic target in GC.

A Decrease of Histone Deacetylase 6 Expression Caused by Helicobacter Pylori Infection is Associated with Oncogenic Transformation in Gastric Cancer

Background: Histone deacetylase 6 (HDAC6) plays a role in the progression of many tumors. However, the relationship between the level of HDAC6 expression and gastric tumorigenesis is still unclear. Here, we illustrate the potential correlation between Helicobacter pylori (HP) infection and the variation of HDAC6 expression in different gastric lesions, as well as the clinical significance of HDAC6 expression in gastric cancer (GC) patients. Materials and Methods: Between 2011 and 2016, 364 patients with different types of gastric lesions were enrolled in Baotou City Central Hospital. Immunostaining of HDAC6 expression and HP infection were performed in the following cohort including 21 normal tissues (Normal); 40 samples with chronic superficial gastritis (CSG); 106 with chronic atrophic gastritis (CAG); 94 with intestinal metaplasia (IM); 64 with dysplasia (DYS) and 39 with gastric cancer (GC). Survival analysis was performed in another 80 GC patients using the Kaplan-Meier method and multivariate Cox regression analyses. The level of HDAC6 expression was determined by Real-time PCR, Western blotting and IHC staining in gastric cell lines and tissues. Furthermore, the correlation between HDAC6 expression and clinicopathological features and prognosis was analyzed in the GC cohort. HP strains were lavaged into Kunming mice to investigate the effects of HP infection on the expression of different HDAC members in this mouse model. Results: Higher levels of HDAC6 expression were detected in normal and premalignant lesions than in the GC tissues (p<0.01), and decreased HDAC6 expression was associated with HP infection and TNM stage (p<0.01 and p=0.048, respectively). Multivariate analysis revealed that HDAC6 expression was an independent predictor of the outcome of GC patients (p=0.04). HP mediated HDAC6 expression in the cell lines and KM mice. HP infection could promote HDAC1 and HDAC4 expression as determined by Western blotting. Conclusions: HDAC6 is a promising biomarker for early diagnosis and prognosis during the oncogenic transformation of gastric cancer.

Clinical Significance of Myeloid Zinc Finger 1 Expression in the Progression of Gastric Tumourigenesis

Background/Aims: To investigate the clinical significance of myeloid zinc finger 1 (MZF1) expression in various gastric mucosal lesions including chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia (DYS) and gastric cancer (GC) in comparison with normal tissues and gastric cell lines. Methods: MZF1 protein expression was detected using immunohistochemical staining in 37 CSG, 88 CAG, 77 IM, 51 DYS, 165 GC and 8 normal tissue samples. Quantitative real-time PCR (qRT-PCR) and western blotting were used to detect the level of MZF1 in gastric cell lines, 15 normal tissues and 34 GC samples, as well as 2 groups of paired primary GC and adjacent normal samples. Results: Reduced MZF1 expression was detected in most GC cells and tissues. Among the gastric tissues consisting of various stages of lesions (normal, CSG, CAG, IM, DYS and GC), MZF1 protein expression was downregulated in precancerous lesions and GC. The data from clinical analyses showed that decreased MZF1 expression was correlated with tumour invasion (p = 0.044), lymph node metastasis (p = 0.048) and poor prognosis of GC patients (p = 0.003). Moreover, MZF1 was identified as an independent prognostic biomarker for GC patients in multivariate Cox regression analysis (p = 0.009). Conclusion: Downregulation of MZF1 was associated with gastric tumourigenesis, which may be a novel early predictive and prognostic biomarker in GC patients.

The Long Noncoding RNA D63785 Regulates Chemotherapy Sensitivity in Human Gastric Cancer by Targeting miR-422a

Gastric cancer is one of the most prevalent tumor types in the world. Chemotherapy is the most common choice for cancer treatment. However, chemotherapy resistance and adverse side effects limit its clinical applications. Aberrant expression of long noncoding RNAs (lncRNAs) has been found in various stages of gastric cancer development and progression. In this study, we identified that an oncogenic lncRNA, long intergenic non-protein-coding RNA D63785 (lncR-D63785), is highly expressed in gastric cancer tissues and cells. Silencing of lncR-D63785 inhibited cell proliferation, cell migration and invasion in gastric cancer cell lines and reduced tumor volume and size in mice. We found that the expression of lncR-D63785 was inversely correlated with microRNA 422a (miR-422a) expression, which was involved in the downregulation of expression of myocyte enhancer factor-2D (MEF2D) and drug sensitivity. Knockdown of lncR-D63785 increased the expression of miR-422a and the sensitivity of gastric cancer cells to apoptosis induced by the anticancer drug doxorubicin (DOX). This indicates that lncR-D63785 acts as a competitive endogenous RNA (ceRNA) of miR-422a and promotes chemoresistance by blocking miR-422-dependent suppression of MEF2D. Together, our results suggest that the therapeutic suppression of lncR-D63785 alone or in combination with chemotherapeutic agents may be a promising strategy for treating gastric cancer.

Germline mutations in patients with multiple colorectal polyps in China.

Multiple colorectal polyps are relevant in hereditary colorectal cancer (CRC) syndromes, which are thought to be caused by multiple events including germline mutations. This study was aimed to characterize germline mutations in Chinese patients with multiple colorectal polyps.

Complete mucosal repair after endoscopic submucosal enucleation of a gastric submucosal tumor assisted by the clip-with-line method

Deep ulcers and even perforations can occur after endoscopic submucosal enucleation (ESE) of gastrointestinal submucosal tumors (SMTs), as most SMTs arise from the muscularis propria layer. If SMTs can be removed by ESE without damaging the overlying normal mucosa, the defects can be completely closed with the remaining normal mucosa. Recently, countertraction has been reported to facilitate resection of gastrointestinal SMTs [1]. In this report, we describe how to use a clip-with-line (CWL) method to facilitate enucleation of an SMT, with the entire overlying normal mucosa preserved to close the defect completely after ESE. A 30-year-old man was admitted to our hospital because of dyspepsia. A gastric SMT was detected endoscopically (▶Fig. 1). Subsequently, endoscopic ultrasound was used to show that the SMT originated in the muscularis propria layer (▶Fig. 2). At the patient’s express request, ESE was performed; written informed consent was obtained before treatment. First, after marking and submucosal injection, a semicircumferential mucosal incision was created using a DualKnife from Olympus (Tokyo, Japan). Submucosal dissection exposed the SMT E-Videos

Predictive factors for technically difficult endoscopic submucosal dissection in large colorectal tumors.

BACKGROUND/AIMS Endoscopic submucosal dissection (ESD) for colorectal tumors is dangerous, particularly those that are large. However, the technical difficulty in resecting large tumors in the colonrectum has seldom been investigated. MATERIALS AND METHODS Between October 2012 and January 2015, 36 consecutive large colorectal tumors were resected by ESD at the endoscopic center of PLA Army General Hospital. Five factors were investigated in predicting the technical difficulty in resecting such tumors. RESULTS En bloc resection, complete (R0) resection, and curative resection rates were 83.33% (30/36), 80.56% (29/36), and 77.78% (28/36), respectively. Tumor location in a flexure was risk a factor for difficult ESD in the colonrectum as measured by perforation (4.55, 0.09-6.25), non-en bloc resection (4.94, 0.10, 9.45), and dissection speed (β±SE: 1.75±0.05). When tumor size increased, the perforation rate also increased (9.93, 0.96-10.32). CONCLUSION ESD was more technically demanding in flexures for resecting large colorectal tumors, and for large tumor effective technique to close perforation is essential. Our study will guide endoscopists in using ESD to remove large colorectal tumors.