Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer.

BACKGROUND: The hunt for the molecular markers with specificity and sensitivity has been a hot area for the tumor treatment. Due to the poor diagnosis and prognosis of pancreatic cancer (PC), the excision rate is often low, which makes it more urgent to find the ideal tumor markers. METHODS: Robust Rank Aggreg (RRA) methods was firstly applied to identify the differentially expressed genes (DEGs) between PC tissues and normal tissues from GSE28735, GSE15471, GSE16515, and GSE101448. Among these DEGs, the highly correlated genes were clustered using WGCNA analysis. The co-expression networks and molecular complex detection (MCODE) Cytoscape app were then performed to find the sub-clusters and confirm 35 candidate genes. For these genes, least absolute shrinkage and selection operator (lasso) regression model was applied and validated to build a diagnostic risk score model. Cox proportional hazard regression analysis was used and validated to build a prognostic model. RESULTS: Based on integrated transcriptomic analysis, we identified a 19 gene module (SYCN, PNLIPRP1, CAP2, GNMT, MAT1A, ABAT, GPT2, ADHFE1, PHGDH, PSAT1, ERP27, PDIA2, MT1H, COMP, COL5A2, FN1, COL1A2, FAP and POSTN) as a specific predictive signature for the diagnosis of PC. Based on the two consideration, accuracy and feasibility, we simplified the diagnostic risk model as a four-gene model: 0.3034*log2(MAT1A)-0.1526*log2(MT1H) + 0.4645*log2(FN1) -0.2244*log2(FAP), log2(gene count). Besides, a four-hub gene module was also identified as prognostic model = - 1.400*log2(CEL) + 1.321*log2(CPA1) + 0.454*log2(POSTN) + 1.011*log2(PM20D1), log2(gene count). CONCLUSION: Integrated transcriptomic analysis identifies two four-hub gene modules as specific predictive signatures for the diagnosis and prognosis of PC, which may bring new sight for the clinical practice of PC.

Comparison of three lymph node staging schemes for predicting the outcome in patients with small bowel adenocarcinoma: A population-based cohort and international multicentre cohort study.

BACKGROUND: The prognostic roles of three common lymph node staging schemes, number of positive lymph nodes (pN), lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) in small bowel adenocarcinoma (SBA) are unclear. We assessed their prognostic ability in SBA. METHODS: A total of 2128 patients diagnosed with SBA between 1988 and 2010 from the Surveillance, Epidemiology, and End Results (SEER) database and 186 patients from 15 hospitals in France and China were identified. We evaluated the prognostic ability of the schemes in both continuous and stratified patterns using R2, Harrell's C, and time-dependent receiver operating characteristic curve analyses. FINDINGS: For continuous pattern, the LODDS had a better capacity of discrimination and higher accuracy of prognosis than pN and LNR. Similarly, the stratified LODDS classification had a better performance of discrimination and higher accuracy of prognosis than the pN and LNR classification. The multivariable model using the LODDS classification also showed superiorly predictive accuracy and discriminatory capacity to those of the 7th and, 8th TNM node and LNR classification. These results were fully validated in an independent international multicentre cohort. INTERPRETATION: The LODDS scheme showed a better prognostic performance than the LNR or pN schemes in patients with SBA regardless of continuous or stratified pattern. The LODDS scheme could serve as an auxiliary to lymph node staging systems in future revisions of the American Joint Committee on Cancer (AJCC) manual. FUND: This work was funded by the Zhejiang Province Natural Science Fund of China.

The 50 Most-cited Articles in Gastroenterology and Hepatology from Mainland China.

OBJECTIVE: To identify and analyze the 50 most-cited gastroenterology and hepatology articles originating from mainland China. METHODS: We utilized the 2015 edition of Journal Citation Reports and PubMed to determine the 50 most-cited gastroenterology and hepatology articles from 75 professional journals and four leading journals in clinical medicine, which are The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The British Medical Journal. Then we excluded the articles written outside mainland China and collected the basic information, including the title, authors, year of publication, source journal, city, institution, number of citations, and topic of the research. RESULTS: The number of citations for the top 50 papers ranged from 279 to 89 (mean, 129). These articles were published between 2005 and 2012, in which 2009 was the year with the largest number of highly cited papers(13). All articles were published in 15 journals. The journal Hepatology published the largest number of articles(21), followed by Journal of Gastroenterology and Hepatology(4), Journal of Hepatology(4) and World Journal of Gastroenterology(4). The top 50 articles originated mainly from Shanghai(20), Guangzhou(13) and Beijing(6). Sun Yat-sen University produced most highly cited papers(10). The number of basic research was far more than clinical research, of which the ratio was about 1.78(32:18). In all these articles, hepatocellular carcinoma was the most-discussed topic(19), followed by hepatitis B virus(8) and endoscopic(5). CONCLUSIONS: Although a large gap remains between mainland China and the global community, the gastroenterology and hepatology research from China is gradually recognized by the world.

Differential expression of Notch1 intracellular domain and p21 proteins, and their clinical significance in gastric cancer.

Changes in the expression of the Notch1 intracellular domain (NICD) and p21 proteins have been shown to be closely associated with the development and progression of a number of cancers. The present study aimed to investigate the expression levels of the two proteins in gastric carcinoma and precancerous lesions, and to determine the clinical significance of this. A total of 109 gastric cancer, 57 precancerous gastric lesion, 50 chronic superficial gastritis and 17 normal gastric mucosa patients were recruited for immunohistochemical staining of NICD and p21 protein expression. The protein expression levels in the gastric cancer patient samples were associated with the clinicopathological and survival data. NICD protein levels were upregulated gradually from normal gastric mucosae through chronic superficial gastritis and precancerous gastric lesions to gastric cancer tissues (P<0.01), whereas p21 protein levels were downregulated accordingly (P<0.01). Increased NICD and a loss of p21 expression were closely associated with tumor dedifferentiation, depth of tumor invasion, lymph node metastasis, surface morphology and Lauren classification in gastric cancer. Thus, NICD expression was inversely associated with p21 expression. In addition, the overall survival rate was greater in NICD- and P21+ patients than in NICD+ and P21- patients, respectively (P<0.05). The COX regression multivariate analysis revealed that NICD+, p21-, depth of tumor invasion and lymph node metastasis were all independent prognostic factors for patients with gastric cancer. NICD and p21 proteins are differentially expressed in gastric cancer and the aberrant expression of these proteins is associated with an advanced tumor stage, tumor metastasis and overall patient survival. Future studies are required to further evaluate the two proteins as novel prognostic markers for patients with gastric cancer.