Expression profiling and long lasting responses to chemotherapy in metastatic gastric cancer

Abstract

Abstract. Current palliative chemotherapy (CT) regimens achieve clinical benefits in less than 50% of patients treated for metastatic gastric cancers, and long-term survivals are anecdotical. Genetic polymorphisms and differences at the level of transcription in genes involved in biological processes of drug metabolism, DNA repair and drug resistance can explain the observed individual differences in response to drugs, in survival and in different susceptibility to the toxic effects of CT. The possibility to classify patients on the basis of genetic signatures could help in choosing the CT regimen. We present herein an analysis of genetic and expression profiling of three patients affected by metastatic gastric cancer, treated with CT and alive, disease-free, at 66-82 months. Four patients with typical clinical outcome represented the control group. Expression profiling from paraffin-embedded tumor tissues was performed on an ad hoc set of genes involved in drug metabolism and resistance, DNA repair, cell cycle regulation and growth factors signalling. Genetic polymorphism analysis on DNA extracted from peripheral blood was done by pyrosequencing of genetic markers predictive of drug response. Expression analysis in long-term survivors revealed a significant upregulation of PTEN, TP63, GADD45a and MAPK1 genes. We found also an upregulation of CYP1A1, CYP3A4 and ERBB4 genes. EGF was found to be down-regulated in long-term survivors. ERCC1 C8092A polymorphism seems to be associated with survival in our set of patients. The present study shed light on a set of genes, which could have a predictive role in survival of patients with metastatic gastric tumors.

Expression of the EGF Family in Gastric Cancer: Downregulation of HER4 and Its Activating Ligand NRG4

“…HER4 protein expression as detected by immunohistochemistry has been found to correlate with early stage, lower grade, and absence of lymph node metastases in gastric cancer [25]. This is in very good agreement with another study that investigated gene expression profiles in long-term survivors from metastatic gastric cancer treated with chemotherapy in which the authors indicated a possible role of HER4 upregulation in these patients [37]. Together with our present results, these data further indicate that HER4 signaling has a protective function against carcinogenesis in the gastric region.…”

Functional Genomics Uncover the Biology behind the Responsiveness of Head and Neck Squamous Cell Cancer Patients to Cetuximab

“…B, the boxplots display the enrichment ssGSEA scores for GS-1, GS-15, and RAS oncogenic gene set and centroid Cl3-hypoxia scores for 1CC8 and SCC1 cells, resistant and sensitive to cetuximab, respectively. extraordinarily long, as already done with some success on another cancer type by others (27).…”

Prediction of progression of chronic atrophic gastritis withHelicobacter pyloriand poor prognosis of gastric cancer by CYP3A4

“…[25][26][27][28][29] Additionally, CYP3A4 was detected to overexpress in gastric cancer by microarray analysis, and it was related with responses to chemotherapy in metastatic gastric cancer. 30,31 CYP3A4 was also expressed in the foveolar epithelium of the human stomach with intestinal metaplasia. 32 In the PPI network, our study found that the gene CYP3A4 had highest scores of the analysis of degree centrality and subgraph centrality.…”

“…CYP3A4 was indicated to have functions in several neoplasms, like hepatocellular carcinoma, breast cancer, lung cancer, prostate cancer, and gastric cancer . Additionally, CYP3A4 was detected to overexpress in gastric cancer by microarray analysis, and it was related with responses to chemotherapy in metastatic gastric cancer . CYP3A4 was also expressed in the foveolar epithelium of the human stomach with intestinal metaplasia .…”