(2007-2010, PN-II-41-036) – Principal investigator: Mihaela Economescu (Chivu) PhD
Aim: This project aimed to perform an etiopathogenetic study on the role of gp130 co-receptor and Jak1, STAT3 signaling pathways in gastric and esophageal carcinoma.
Partners: Coordinator: Stefan S. Nicolau Institute of Virology– principal investigator Mihaela Economescu (Chivu) PhD.
Partner 1 – Floreasca Emergency Clinical Hospital, principal investigator Gabriel CONSTANTINESCU, MD, PhD
Partner 2: Fundeni Clinical Institute – principal investigator Prof. Irinel Popescu MD, PhD
Funding: 750.000 RON
Working team: Stoian Mihai, Diaconu Carmen Cristina, Anton Gabriela, Zaharia Corneliu Nicolae, Bleotu Coralia, Irina Alexiu, Neagu Ana Iulia, Nastasie Alina, Dragomir Laura, Dragu Denisa, Stancu I Cosmin, Dragusel Roxana, Matei Lilia, Fratilescu Milica, Ivan Doina, Marginean Georgeta, Mustatea Steluta, Harcu Lucica, Petre Niculina, Tiron Brenda, Badea Ion.
Project financed by MEC, PN-II contract no. 41-036/2007
Implementation period: September 2007 – September 2010
Summary: This study aimed to characterize changes in the gene expression profile in patients with gastric adenocarcinoma, based on tumor stage, and identify candidate genes involved in tumor progression and metastasis. In order to obtain a molecular-level image of gastric tumorigenesis, significantly modified genes were examined in terms of molecular functions, interactions, and their involvement in signaling pathways. Gene expression data was obtained using immunoblot, ELISA, sequencing, microarray, and quantitative RT-PCR techniques. The results showed several changes in normal biological processes that were associated with the primary or advanced stage of gastric adenocarcinoma. In primary lesions, intense metabolic processes were observed (with regard to triglycerides, collagen, and glycerol), as well as an increase in expression level of protease, genes related to morphogenesis and biosynthesis processes. Additionally, in advanced gastric adenocarcinoma, overexpressed genes known to be involved in cytoskeleton rearrangement, cell migration, regulation of phosphorylation processes, and anti-apoptosis were found. Moreover, in this study, a significant association was identified between tumor stage and mRNA expression level for 7 genes: IL11, S100A2, MMP3, KRT17, SPP1, KIAA1199, and COL10A1, which may become markers of tumor progression. Thus, COL10A1 and KRT17, together with SALL4, can be used as biomarkers in early detection because their increased expression occurs in the early stage of the tumor and remains elevated during tumor progression. All these results led to the development of a molecular screening protocol for evaluating disease progression and prognostic index in gastric ADK, which will be recommended to medical facilities for improving medical services. Another direct result of the project is the tumor bank, which contains samples from 61 cases (tumor and adjacent normal tissue fragments, plasma, extracted nucleic acids, primary cell cultures). The bank has a computerized database that can be quickly accessed for extracting different indicators. The bank can be a starting point for future studies, being particularly useful due to the well-characterized and preserved biological material stored.
- Mihaela Chivu Economescu, Laura G. Necula, Denisa Dragu, Liviu Badea, Simona O. Dima, Stefan Tudor, Anca Nastase, Irinel Popescu, Carmen C. Diaconu, Identification of potential biomarkers for early and advanced gastric adenocarcinoma detection, Hepato-Gastroenterology, 2010, 58(104): 1453-1464 (ISSN: 0172-6390, ISI, IF=0.677
- Necula LG, Chivu-Economescu M, Stanciulescu EL, Bleotu C, Dima SO, Alexiu I, Dumitru A, Constantinescu G, Popescu I, Diaconu CC. IL-6 and IL-11 as markers for tumor aggressiveness and prognostic in gastric adenocarcinoma patients without mutations in gp130 subunit. Journal of Gastrointestinal and Liver Diseases 2012, 21(1), 23-29. (ISSN: 1841-8724). IF=1.855
Communications at national/international congresses
- Mihaela Chivu, Laura G. Necula, Adriana Dumitru, Liliana Dumitru, Simona O. Dima, Anca Nastase, Liviu Badea, Gabriel Constantinescu, Irinel Popescu, Carmen C. Diaconu. IL11 and STAT3 as potential biomarkers for gastric adenocarcinoma progression, FEBS Special Meeting: JAK/STAT signaling: From Basics to Disease, 10-13 February 2010, Vienna, Austria, p64.
- Laura G. Necula, Mihaela Chivu, Coralia Bleotu, Adriana Dumitru, Liliana Dumitru, Gabriel Constantinescu, Simona O. Dima, Irinel Popescu, Carmen C. Diaconu. Evidence of STAT3 hyperactivity in serum and mucosa of patients with gastric cancer, FEBS Special Meeting: JAK/STAT signaling: From Basics to Disease, 10-13 February 2010, Vienna, Austria, p113.