Association between epithelial‐mesenchymal transition and cancer stemness and their effect on the prognosis of lung adenocarcinoma

Abstract

The epithelial‐mesenchymal transition (EMT) and cancer stemness (CS) are reported to be pivotal phenomena involved in metastasis, recurrence, and drug‐resistance in lung cancer; however, their effects on tumor malignancy in clinical settings are not completely understood. The mutual association between these factors also remains elusive and are worthy of investigation. The purpose of this study was to elucidate the association between EMT and CS, and their effect on the prognosis of patients with lung adenocarcinoma. A total of 239 lung adenocarcinoma specimens were collected from patients who had undergone surgery at Kyoto University Hospital from January 2001 to December 2007. Both EMT (E‐cadherin,vimentin) and CS (CD133, CD44, aldehyde dehydrogenase) markers were analyzed through immunostaining of tumor specimens. The association between EMT and CS as well as the patients' clinical information was integrated and statistically analyzed. The molecular expression of E‐cadherin, vimentin, and CD133 were significantly correlated with prognosis (P = 0.003, P = 0.005, and P < 0.001). A negative correlation was found between E‐cadherin and vimentin expression (P < 0.001), whereas, a positive correlation was found between vimentin and CD133 expression (P = 0.020). CD133 was a stronger prognostic factor than an EMT marker. Elevated CD133 expression is the signature marker of EMT and CS association in lung adenocarcinoma. EMT and CS are associated in lung adenocarcinoma. Importantly, CD133 is suggested to be the key factor that links EMT and CS, thereby exacerbating tumor progression.

CDH1 (E-cadherin) expression independently affects clinical outcome in acute myeloid leukemia with normal cytogenetics

“…Therefore, these approaches targeting CDH1 may point out new orientations and hope for cancer treatment through gene-targeted therapies. Although E-cadherin was widely investigated in various solid tumors, its expression and prognostic value in hematologic malignancies especially in AML were poorly mentioned [35][36][37]. In the current study, CDH1 was significantly downregulated in AML patients as compared with healthy donors.…”

Hypoxia‐inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX expression

“…Although some studies have reported the importance of CAIX in prognosis of lung cancer patients , the exact mechanism remains unclear. On the other hand, our analysis of 239 resected lung adenocarcinoma specimens at our institute did not show the association of CAIX expression with patient prognosis (data not shown) . These results may provide new insights on using CAIX as a target for treating advanced lung cancer requiring induction chemoradiotherapy.…”

L1 Cell Adhesion Molecule Confers Radioresistance to Ovarian Cancer and Defines a New Cancer Stem Cell Population

“…Our results also demonstrated that CD133 expression increased in IGROV1 ∆L1CAM cells. In lung adenocarcinoma, elevated expression CD133 is a signature marker of EMT [35]. Recent studies have highlighted a link between EMT and CSC formation, indicating that stem cell-properties emerge during progression of EMT and stemness seems to be important to regulate invasive potential [36].…”