Prognostic role of annexin A2 and cancer-associated fibroblasts in advanced non-small cell lung cancer: Implication in epithelial-mesenchymal transition and gefitinib resistance.

BACKGROUND: Despite advances in treatment of non-small cell lung cancer (NSCLC), its prognosis remains dismal. Development of drug resistance is a major obstacle against success of targeted epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitors (TKI) therapy. This study aimed to assess the prognostic role of annexin A2 (ANXA2) expression, within both tumor cells and stroma, as well as cancer associated fibroblasts (CAFs) in NSCLC and to investigate their potential role in induction of epithelial mesenchymal transition (EMT) and resistance to gefitinib. METHOD: Immunohistochemistry was performed to evaluate tumoral and stromal ANXA2 expression and α-SMA-stained CAFs in 110 advanced NSCLC patients. Furthermore, STAT3 and E-cadherin mRNA expression was studied by quantitative reverse transcription PCR (qRT-PCR). RESULTS: Both tumoral and stromal ANXA2 as well as CAFs were significantly related to clinical stage IV and malignant pleural effusion, while tumoral ANXA2 was significantly related to poor tumor differentiation. EGFR mutation and high tumoral ANXA2 were independent factors for poor overall survival, whereas high stromal and tumoral ANXA2 and high CAFs were independent predictors for poor progression-free survival. Moreover, high ANXA2 and CAFs were significantly associated with high STAT3 and low E-cadherin mRNA expression. Focusing on EGFR mutated cases, gefitinib resistance was significantly associated with high tumoral and stromal ANXA2, high CAFs, high STAT3 and low E-cadherin. CONCLUSION: CAFs and ANXA2 could be considered as poor prognostic parameters in advanced NSCLC and are potential factors for gefitinib therapy resistance through EMT induction.

Oct4 expression in gastric carcinoma: association with tumor proliferation, angiogenesis and survival.

BACKGROUND: Octamer-binding transcription factor 4 (Oct4) is a transcription factor that has an important role in stem cell differentiation and self-renewal. Oct4 has also been implicated in tumorigenicity of different cancers. This study aimed to analyze Oct4 expression in gastric carcinoma (GC) and to evaluate the relation between Oct4 expression and clinicopathologic parameters, tumor proliferation, and angiogenesis in addition to patient survival. RESULTS: Oct4 mRNA was detected by quantitative reverse transcription PCR (qRT-PCR) in 45 GC specimens and adjacent non-cancerous tissues. We found a significant difference in Oct4 mRNA relative expression levels in GC tissue compared with adjacent non-cancerous tissues (p < 0.001). Furthermore, immunohistochemistry (IHC) was performed to study the Oct4 expression in GC cases. High Oct4 immunostaining was detected in 62.2% of GC specimens. High Oct4 expression both by mRNA relative quantitation and IHC were significantly related to poorly differentiated tumors, nodal metastasis, and stage III tumors. Moreover, high Oct4 IHC expression was also associated with cases positive for Ki-67 and VEGF expressions (p < 0.001 and 0.021, respectively). Oct4 expression identified by both mRNA relative quantitation and IHC was significantly related (p < 0.001). As regards patient survival, high Oct4 expression was significantly related to poor overall survival (OS) and disease-free survival (DFS) (p = 0.029 and 0.031, respectively). CONCLUSION: Oct4 plays a valuable role in the progression and prognosis of GC. High Oct4 expression is associated with high tumor grade, nodal metastasis, stage III tumors, and poor OS and DFS. High Oct4 is also significantly associated with Ki-67 and VGEF expression, thus enhancing tumor proliferation and angiogenesis.