Prognostic value of hypoxia-inducible factor-1 alpha and prolyl 4-hydroxylase beta polypeptide overexpression in gastric cancer

AIM To investigate the relationship between hypoxia-inducible factor-1α(HIF-1α), prolyl 4-hydroxylase beta(P4 HB) expression, and clinicopathologic parameters, as well as the prognostic value of these genes for patients with gastric cancer(Gc).METHODS Hypoxia is a critical factor that shapes the Gc microenvironment. In previous reports, we have demonstrated that P4 HB is a potential target of HIF-1α. In the present study, gene expression profiling interactive analysis(GEPIA) was used to analyze the relationship between P4 HB and hypoxia-associated genes. To this end, 428 Gc tissue samples were used to analyze the expression of HIF-1α and P4 HB via immunohistochemical staining. Patient samples were classified as having weak-expression or over-expression both in terms of HIF-1α and P4 HB. Correlations between biomarkers and clinicopathological factors were analyzed to predict survival. RESULTS P4 HB demonstrated a positive correlation with hypoxiaassociated genes(P < 0.05). HIF-1α and P4 HB overexpression have a significant correlation with TNM staging(χ2 = 23.32, P = 0.00; χ2 = 65.64, P = 0.00) and peritoneum cavity metastasis(χ2 = 12.67, P = 0.00; χ2 = 39.29, P = 0.00). In univariate analysis, patients with a high HIF-1α expression trend had a shorter disease-free survival(DFS: 44.80 mo vs 22.06 mo) and overall survival(OS: 49.58 mo vs 39.92 mo). P4 HB overexpression reflected similar results: patients with over-expression of P4 HB had a shorter survival time than those with weak-expression(DFS: 48.03 mo vs 29.64 mo, OS: 52.48 mo vs 36.87 mo). Furthermore, HIF-1α is also a clinicopathological predictor of dismal prognosis according to multivariate analysis(DFS, 95%c I: 0.52-0.88, P < 0.00; OS, 95%c I: 0.50-0.85, P < 0.00). However, P4 HB was meaningful in DFS(95%c I: 0.58-1.00, P < 0.05) but not in OS(95%c I: 0.72-1.23, P > 0.05).CONCLUSION Overexpression of HIF-1α and P4 HB is associated with poor prognosis in patients with Gc. Thus, these genes may be potential prognostic biomarker candidates in GC.

Surgical resection of esophagogastric junction stromal tumor: How to protect the cardiac function

BACKGROUND Various surgical procedures have been described for gastrointestinal stromal tumors(GISTs)at the esophagogastric junction(EGJ)close to the Z-line.However,surgery for EGJ-GIST involving Z-line has been rarely reported.AIM To introduce a novel technique called conformal resection(CR)for open resection of EGJ-GIST involving Z-line.METHODS In this retrospective study,43 patients having GISTs involving Z-line were included.The perioperative outcomes of patients receiving CR(n=18)was compared with that of proximal gastrectomy(PG)(n=25).RESULTS CR was successfully performed in all the patients with negative microscopic margins.The mean operative time,time to first passage of flatus,and postoperative hospital stay was significantly shorter in the CR group(P<0.05),while the intraoperative blood loss was similar in the two groups.The postoperative gastroesophageal reflux as diagnosed by esophageal 24-h pH monitoring and quality of life at 3 mo were significantly in favor of CR compared to PG(both P<0.001).The 5-year disease-free survival between the two groups was similar(P=0.163).The cut-off value for the determination of CR or PG was 7.0 mm above the Z-line(83.33%sensitivity,84.00%specificity,83.72%accuracy).CONCLUSION CR is safe and feasible for EGJ-GIST located within 7.0 mm above the Z-line.

Effects of post-annealing on crystalline and transport properties of Bi_(2)Te_(3) thin films

A well-established method is highly desirable for growing topological insulator thin films with low carrier density on a wafer-level scale. Here, we present a simple, scalable method based on magnetron sputtering to obtain high-quality Bi_(2) Te_(3) films with the carrier density down to 4.0 × 10^(13) cm^(-2). In contrast to the most-used method of high substrate temperature growth, we firstly sputtered Bi_(2) Te_(3) thin films at room temperature and then applied post-annealing. It enables the growth of highly-oriented Bi_(2) Te_(3) thin films with larger grain size and smoother interface. The results of electrical transport show that it has a lower carrier density as well as a larger coherent length(~ 228 nm, 2 K). Our studies pave the way toward large-scale, cost-effective production of Bi_(2) Te_(3) thin films to be integrated with other materials in wafer-level scale for electronic and spintronic applications.

Prognostic value of sorting nexin 10 weak expression in stomach adenocarcinoma revealed by weighted gene coexpression network analysis

AIM TO detect significant clusters of co-expressed genes associated with tumorigenesis that might help to predict stomach adenocarcinoma （SA） prognosis.METHODS The Cancer Genome Atlas database was used to obtain RNA sequences as well as complete clinical data of SA and adjacent normal tissues from patients. Weighted gene co-expression network analysis （WGCNA） was used to investigate the meaningful module along with hub genes. Expression of hub genes was analyzed in 362 paraffin-embedded SA biopsy tissues by immunohistochemical staining. Patients were classified into two groups （according to expression of hub genes）： Weak expression and over-expression groups. Correlation of biomarkers with clinicopathological factors indicated patient survival.RESULTS Whole genome expression level screening identified 6,231 differentially expressed genes. Twenty-four co- expressed gene modules were identified using WGCNA. Pearson＇s correlation analysis showed that the tan module was the most relevant to tumor stage （r = 0.24, P = 7 × 10 -6）. In addition, we detected sorting nexin （SNX）10 as the hub gene of the tan module. SNX10 expression was linked to T category （P = 0.042, x2= 8.708）, N category （P = 0.000, x2= 18.778）, TNM stage （P = 0.001, x2 = 16.744） as well as tumor differentiation （P = 0.000,x2= 251.930）. Patients with high SNX10 expression tended to have longer diseasefree survival （DFS; 44.97 mo vs 33.85 mo, P = 0.000） as well as overall survival （OS; 49.95 vs 40.84 mo, P = 0.000） in univariate analysis. Multivariate analysis showed that dismal prognosis could be precisely predicted clinicopathologically using SNX10 [DFS： P = 0.014, hazard ratio （HR） = 0.698, 95% confidence interval （CI）： 0.524-0.930, OS： P = 0.017, HR = 0.704, 95%CI： 0.528-0.940].CONCLUSION This study provides a new technique for screening prognostic biomarkers of SA. Weak expression of SNX10 is linked to poor prognosis, and is a suitable prognostic biomarker of SA.

Cellular Anchorage Sensing and Anoikis

Normal epithelial cells that lose the integrindependent anchorage to their extracellular matrix trigger anoikis,while metastatic tumor cells bypass anoikis pathway, which is one of the key events to achieve the metastasis. Physiological role of anoikis is also involved during embryonic development and tissue homeostasis, suggesting that anoikis must be strictly regulated at some level. Despite its importance, the molecular pathways involved in the regulation of anoikis and the proximal signals reporting loss of anchorage are poorly understood. Recent studies suggest an adaptor protein p66Shc, localizing at focal adhesions,mediates anoikis through activation of RhoA. However, expression of p66Shc is inadequate in metastatic cancer cells, failing to initiate anoikis and promoting tumor metastasis. Reexpression of proapoptotic protein p66Shc can restore the susceptibility to anoikis.Thus, p66Shc may be a potential target molecule for diagnosis of tumor metastasis and for tumor treatment.