Significance and relationship between Yes-associated protein and survivin expression in gastric carcinoma and precancerous lesions

AIM:To analyze the differences and relevance of Yes-associated protein (YAP) and survivin, and to explore the correlation and signifi cance of their expression in gastric carcinoma and precancerous lesions.METHODS: The PV9000 immunohistochemical method was used to detect the expression of YAP and survivin in 98 cases of normal gastric mucosa, 58 intestinal metaplasia (IM), 32 dysplasia and 98 gastric carcinoma.RESULTS: The positive rates of YAP in dysplasia (37.5%) and gastric carcinoma (48.0%) were significantly higher than that in normal gastric mucosa (13.3%), P<0.01. The positive rates of survivin in IM (53.4%), dysplasia (59.4%) and gastric carcinoma (65.3%) were significantly higher than in normal gastric mucosa (11.2%), P<0.01. Survivin expression gradually increased from 41.7% in well differentiated adenocarcinoma through 58.3% in moderately differentiated adenocarcinoma to 75.6% in poorly differentiated adenocarcinoma, with significant Rank correlation, rk=0.279, P<0.01. The positive rate of survivin in gastric carcinoma of diffused type (74.6%) was significantly higher than that in intestinal type (51.3%), P<0.05. In gastric carcinoma with lymph node metastasis (76.9%), the positive rate of survivin was signifi cantly higher than that in the group without lymph node metastasis (41.2%), P<0.01. In 98 cases of gastric carcinoma, the expression of YAP and of survivin were positively correlated, rk=0.246, P<0.01.CONCLUSION: YAP may play an important role as a carcinogenic factor and may induce survivin expression. Detecting both markers together may help in early diagnosis of gastric carcinoma.

Involvement of parathyroid hormone-related peptide in the aggressive phenotype of colorectal cancer cells

Colorectal cancer(CRC)remains one of the leading causes of mortality from malignant diseases worldwide.In general terms,CRC presents high heterogeneity due to the influence of different genetic and environmental factors;also,the neoplastic cells are strongly influenced by the extracellular matrix and several surrounding cells,known together as the tumor microenvironment(TME).Bidirectional communication takes place between the tumor and the TME through the release of autocrine and paracrine factors.Parathyroid hormone-related peptide(PTHrP)is a cytokine secreted by a wide variety of tissues and is able to regulate several cellular functions both in physiological as well as in pathological processes.It exerts its effects as a paracrine/autocrine factor,although its mode of action is mainly paracrine.It has been shown that this peptide is expressed by several tumors and that the tumor secretion of PTHrP is responsible for the malignant humoral hypercalcemia.Eight years ago,when our research group started studying PTHrP effects in the experimental models derived from intestinal tumors,the literature available at the time addressing the effects of PTHrP on colorectal tumors was limited,and no articles had been published regarding to the paracrine action of PTHrP in CRC cells.Based on this and on our previous findings regarding the role of PTH in CRC cells,our purpose in recent years has been to explore the role of PTHrP in CRC.We analyzed the behavior of CRC cells treated with exogenous PTHrP,focalizing in the study of the following events:Survival,cell cycle progression and proliferation,migration,chemoresistance,tumor-associated angiogenesis,epithelial to mesenchymal transition program and other events also associated with invasion,such us the induction of cancer stem cells features.This work summarizes the major findings obtained by our investigation group using in vitro and in vivo CRC models that evidence the participation of PTHrP in the acquisition of an aggressive phenotype of CRC cells and the molecular mechanisms involved in these processes.Recently,we found that this cytokine induces this malignant behavior not only by its direct action on these intestinal cells but also through its influence on cells derived from TME,promoting a communication between CRC cells and surrounding cells that contributes to the molecular and morphological changes observed in CRC cells.These investigations establish the basis for our next studies in order to address the clinical applicability of our findings.Recognizing the factors and mechanisms that promote invasion in CRC cells,evasion to the cytotoxic effects of current CRC therapies and thus metastasis is decisive for the identification of new markers with the potential to improve early diagnosis and/or to predict prognosis,to predetermine drug resistance and to provide treatment guidelines that include targeted therapies for this disease.

Identification of Proteins and Genes Associated with Hedgehog Signaling Pathway Involved in Neoplasm Formation Using Text-Mining Approach

Analysis of molecular mechanisms that lead to the development of various types of tumors is essential for biology and medicine,because it may help to find new therapeutic opportunities for cancer treatment and cure including personalized treatment approaches.One of the pathways known to be important for the development of neoplastic diseases and pathological processes is the Hedgehog signaling pathway that normally controls human embryonic development.Systematic accumulation of various types of biological data,including interactions between proteins,regulation of genes transcription,proteomics,and metabolomics experiments results,allows the application of computational analysis of these big data for identification of key molecular mechanisms of certain diseases and pathologies and promising therapeutic targets.The aim of this study is to develop a computational approach for revealing associations between human proteins and genes interacting with the Hedgehog pathway components,as well as for identifying their roles in the development of various types of tumors.We automatically collect sets of abstract texts from the NCBI PubMed bibliographic database.For recognition of the Hedgehog pathway proteins and genes and neoplastic diseases we use a dictionary-based named entity recognition approach,while for all other proteins and genes machine learning method is used.For association extraction,we develop a set of semantic rules.We complete the results of the text analysis with the gene set enrichment analysis.The identified key pathways that may influence the Hedgehog pathway and their roles in tumor development are then verified using the information in the literature.