BACKGROUND Long noncoding RNA (lncRNA) ZNFX1-AS1 (ZFAS1) is a newly discovered lncRNA, but its diagnostic value in gastric cancer is unclear. AIM To investigate the potential role of ZFAS1 in gastric cancer and to evaluate the clinical significance of ZFAS1 as a biomarker for gastric cancer screening. METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) was used to screen for gastric cancer-associated lncRNAs in gastric cancer patients, gastric stromal tumor patients, gastritis or gastric ulcer patients, and healthy controls. Correlations between ZFAS1 expression and clinicopathological features were analyzed. The biological effects of ZFAS1 on the proliferation, migration, and invasion of gastric cancer cells were studied by MTT, colony formation, and transwell mi-gration assays. The potential mechanism of ZFAS1 was demonstrated using enzyme-linked immunosorbent assay and qRT-PCR. The relationship between ZFAS1 and tumorigenesis was demonstrated using in vivo tumor formation assays. RESULTS The plasma level of lncRNA ZFAS1 was significantly higher in preoperative patients with gastric cancer than in individuals in the other 4 groups. Increased expression of ZFAS1 was significantly associated with lymph node metastasis, advanced TNM stage, and poor prognosis. ZFAS1 regulated the proliferation, migration, and invasion of gastric cancer cells and regulated the growth of gastric cancer cells in vivo. LIN28 and CAPRIN1 were identified as key downstream mediators of ZFAS1 in gastric cancer cells. CONCLUSION LncRNA ZFAS1 promoted the invasion and proliferation of gastric cancer cells by modulating LIN28 and CAPRIN1 expression, suggesting that ZFAS1 can be used as a potential diagnostic and prognostic biomarker in gastric cancer.

OBJECTIVE:Breast cancer is recognized as the most common cause of malignancy and cancer death worldwide; however, mutations in the cancer-related BRCA genes are detected in only 2-3% of patients with breast cancer. Because next-generation sequencing technology allows concurrent sequencing of numerous target genes, diverse cancer-susceptibility genes are now being evaluated, although their significance in clinical practice remains unclear.METHODS:In this study, we developed a sequencing panel containing the genes BRCA1, BRCA2, TP53, PIK3CA, ERBB2 (Her2), and PTEN, which are all associated with cancer risk in patients, and we enrolled 60 patients with breast cancer.RESULTS:Germline mutations were found to be carried by nine patients (15%): 3 in BRCA1, 5 in BRCA2, and 1 in TP53. The patients harboring these mutations are considered to face a high risk of developing malignant tumors, and cancer screening is thus recommended for the patients.CONCLUSION:This study demonstrates the feasibility of using Ion Torrent sequencing technology for reliably detecting gene mutations in clinical practice for guiding individualized drug therapy or combination therapies for breast cancer.

Objective: To compare eradication rates and compliance of patients with Helicobacter pylori(H. pylori)infection based on clarithromycin sensitivity. Methods: From July 2015 to January 2018,patients with H. pylori infection in Peking university people's hospital were randomly assignedto a 14-day treatment with clarithromycin quadruple therapy versus tailored quadruple therapy for a prospective study. In the group of tailored therapy, medications were adjusted based on clarithromycin sensitivity. In the control group, all patients were given proton pump inhibitors (PPI), amoxicillin, clarithomycin and bismuth. Eradication status was assessed 4 weeks after treatment withurea breath test. Results: The H.pylori eradication rate were higher in the tailor therapy group than that in the control group in intention-to-treat[77.8% vs 65.3%,(P=0.001)] and per,protocol analyses [86.4% vs 70.2%,(P<0.001)], the differences between the two groups were statistically significant.The incidence of compliance between the two groups were also comparable. Conclusions: The tailored therapy basedon clarithromycinsensitivity has a better eradication efficacy and a higher eradication ratesin the patients with H. pylori infection.

Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in different types of cancer, including gastric cancer. Although altered lncRNAs profiles have been observed in or around gastric cancer tissues, the diagnostic value of circulating lncRNAs in gastric cancer remains unclear. In the present study, a number of highly expressed lncRNAs, including uc001lsz, GACAT2, ABHD11-AS1, GACAT3, SUMP1P3, CHET1, TUG1, SNHG12, GAS5, PVT1, LINC00152, HOTAIR, CCAT1, H19, HULC and ZNFX1-AS1, were investigated as potential minimally invasive biomarkers for this tumor. Preliminary screening experiments revealed that ZNFX1-AS1 and HULC were differentially expressed in the plasma of gastric cancer patients and healthy control subjects. The study further examined the relative expression of ZNFX1-AS1 and HULC in the plasma of 50 matching preoperative and postoperative patients, 50 gastrointestinal stromal tumor (GIST) patients, 50 gastritis/peptic ulcer patients and 50 healthy control subjects through reverse transcription-quantitative polymerase chain reaction. The correlation of lncRNA relative expression with the general characteristics and clinicopathological factors was analyzed. It was observed that the levels of ZNFX1-AS1 and HULC in the plasma of preoperative patients were markedly higher compared with those in the plasma of GIST patients, gastritis/peptic ulcer patients and healthy control subjects, while no significant difference was detected among these three groups. Receiver operating characteristic curve analysis was also conducted to distinguish gastric cancer patients from healthy control subjects. The area under the curve was 0.85 and 0.65 for ZNFX1-AS1 and HULC, respectively. In conclusion, the results indicated that the lncRNAs ZNFX1-AS1 and HULC are promising in the clinical diagnosis of gastric cancer.

Objective To evaluate different methods in detecting intraperitontal free cancer cells (IFCCs) in patients with gastric cancer and to clarify the relationship between positive IFCCs and short-term prognosis.Methods A total of 119 gastric cancer patients who underwent surgical treatment were enrolled.Peritoneal lavage was performed with 300-400 ml saline respectively at three points of time:immediately after abdominal cavity entry;when surgical operation was completed;when extensive intraoperative peritoneal lavage was done.The IFCCs were detected with methods of traditional centrifugal cytology,membrane cytology,ICC and RT-PCR.The survival curve of patients with gastric cancer was drawn using Kaplan-Meier method.Results The positive rate of PLC was 16.8％,20.7％ and 11.2％ respectively at 3 timepoints (P ＜ 0.05).The positive rates of ICC were 28.6％,38.8％ and 20.7％ respectively at 3 timepoints.The positive rates of RT-PCR were 39.3％,69.5％ and 50.8％ respectively at 3 time points.The positive rate of IFCCs detected through RT-PCR was higher than that of PLC and ICC (P ＜ 0.05).The short-term prognosis of patients with positive IFCCs was worse than those with negative results detected with any three method at the timg point immediately after opening the abdomen (P ＜ 0.05).At the timg point immediately after removing the tumors,the short-term prognosis of patients with positive IFCCs detected with PLC was worse (P ＜ 0.05).Conclusion The short-term prognosis was poor in patients with positive IFCCs.It is the best time to detect IFCCs before radical resection.Surgical procedures increase the risk of shedding of IFCCs.

In the clinical treatment of lung cancer, therapy failure is mainly caused by cancer metastasis and drug resistance. Here, we investigated whether the tyrosine phosphatase Shp2 is involved in the development of metastasis and drug resistance in non-small cell lung cancer (NSCLC). Shp2 was overexpressed in a subset of lung cancer tissues, and Shp2 knockdown in lung cancer cells inhibited cell proliferation and migration, downregulated c-Myc and fibronectin expression, and upregulated E-cadherin expression. In H1975 cells, which carry double mutations (L858R + T790M) in epidermal growth factor receptor (EGFR) that confers resistance toward the tyrosine kinase inhibitor gefitinib, Shp2 knockdown increased cellular sensitivity to gefitinib; conversely, in H292 cells, which express wild-type EGFR and are sensitive to gefitinib, Shp2 overexpression increased cellular resistance to gefitinib. Moreover, by overexpressing Shp2 or using U0126, a small-molecule inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2), we demonstrated that Shp2 inhibited E-cadherin expression and enhanced the expression of fibronectin and c-Myc through activation of the ERK1/2 pathway. Our findings reveal that Shp2 is overexpressed in clinical samples of NSCLC and that Shp2 knockdown reduces the proliferation and migration of lung cancer cells, and further suggest that co-inhibition of EGFR and Shp2 is an effective approach for overcoming EGFR T790M mutation acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Thus, we propose that Shp2 could serve as a new biomarker in the treatment of NSCLC.

Objective To investigate the distribution of acetaldehyde dehydrogenase 2 (ALDH2) gene polymorphism,and to evaluate the feasibility of allele specific fluorescence polymerase chain reaction (PCR) for ALDH2 gene polymorphism. Methods Allele specific fluorescence PCR and DNA sequencing were used for ALDH2 genotyping in peripheral blood of 375 patients. Gene chip method was adopted to determine the specimens with inconsistent results by the 2 methods. Results Among the 375 specimens,248 cases (66.1%) of ALDH2*1/ 1, 107 cases (28.5%) of ALDH2*1/ 2 and 20 cases (5.4%) of ALDH2*2/ 2 were determined by allele specific fluorescence PCR,while 246 cases (65.6%) of ALDH2*1/ 1,108 cases (28.8%) of ALDH2*1/ 2 and 21 cases (5.6%) of ALDH2*2/ 2 were determined by DNA sequencing,respectively. There was no statistical significance for ALDH2 genotyping between allele specific fluorescence PCR and DNA sequencing (χ2=1.33,P=0.392), with good consistency(κ=0.978,P<0.001). The coincidence rate was 98.9% (371/375)between the 2 methods. For 4 cases with inconsistent results,the results of gene chip method was in agreement with those by allele specific fluorescence PCR. Conclusions Allele specific fluorescence PCR for ALDH2 genotyping is feasible,and could meet the requirements of clinical ALDH2 gene determination.

目的 用TaqMan-MGB荧光探针法检测北京地区幽门螺杆菌克拉霉素耐药位点A2142G、A2143G突变情况.方法 收集北京大学人民医院消化科门诊尿素酶试验及病理活检均阳性的患者233例,所有患者均应用MGB荧光探针法和一代测序法对耐药位点A2142G/A2143G进行检测,其中79例患者同时进行传统培养联合药敏法检测.分析耐药位点突变发生率与患者年龄、性别和消化性溃疡的关系.结果 79例传统培养联合药敏法检测的标本中成功培养出42例,占53％(42/79),其中耐药型菌株22例,敏感型菌株20例,而MGB荧光探针法成功检出77例,占97％(77/79),其中野生型28例,突变型49例.在传统培养+药敏法培养出的42例阳性标本中,两种方法检出的符合率为86％(36/42).233例标本中,一代测序法成功检测出214例,占92％(214/233),其中野生型138例,突变型76例.在76例突变型标本中,含A2142G突变(包括A2142G和A2142G+野生)的标本占5％(4/76),含A2143G突变(包括A2143G和A2143G+野生)的标本占95％(72/76).MGB荧光探针法成功检测出231例,占99％(231/233),其中野生型141例,突变型90例.在90例突变型标本中,含A2142G突变的标本占14％ (13/90),含A2143G突变的标本占86％(77/90).一代测序法和MGB荧光探针法在区分是否含有突变上的符合率为95％ (203/214).根据MGB荧光探针法检测结果将患者分为突变组与野生组,2组在年龄和性别上差异无统计学意义(t年龄=-0.685,P=0.4 93;x2性别=0.065,P=0.890),而在消化性溃疡发生率上差异存在统计学意义(x2=6.653,P=0.044).结论 TaqMan MGB荧光探针法可应用于临床快速、敏感地检测患者胃黏膜标本中幽门螺杆菌克拉霉素A2142G、A2143G耐药位点突变情况.