EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas

Abstract

BackgroundSquamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer (NSCLC). Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC.MethodsTwo independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro.ResultsEMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration.ConclusionsEMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy.

Claudin-3 Inhibits Lung Squamous Cell Carcinoma Cell Epithelial-mesenchymal Transition and Invasion via Suppression of the Wnt/β-catenin Signaling Pathway

“…However, the migration capacity of H520 cells was restrained after upregulation of E-cadherin expression through CLDN3 overexpression, whereas the migration ability of SK-MES-1 cells was induced after downregulation of E-cadherin expression using CLDN3 shRNA transduction. Our current data were consistent with previous studies 38 , 39 .…”

“…Our own study also revealed that loss of E-cadherin expression was associated with the lymph node metastasis of lung SqCC and that loss of E-cadherin expression but increased β-catenin expression was associated with lung SqCC recurrence. Other previous studies of lung SqCC cell lines have shown that the migration ability of H2170 and H1703 cells was significantly upregulated after downregulation of E-cadherin expression 38 , 39 . In our current study, we found that reduced CLDN3 expression was associated with loss of E-cadherin expression in lung SqCC specimens but inversely associated with Vimentin expression, compared with the paired adjacent normal tissues.…”

KIAA1522 is a novel prognostic biomarker in patients with non-small cell lung cancer

“…Adjuvant platinum-based chemotherapy remains the mainstay of treatment for non-small cell lung cancer. Though many predictive markers have been assessed 24 25 26 27 28 29 , no molecular marker has been shown to be useful for patient selection until recently. Besides the prognostic role, our present work also showed that high expression of KIAA1522 predicted poor responses for platinum-based chemotherapy, making it a potential biomarker of platinum-resistance.…”

Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma

“…LADC cells commonly exhibit abnormal gene expression patterns and large numbers of gene mutations [ 2 ], and are characterized by specific biomarkers[ 3 – 7 ] and prognostic factors [ 8 – 10 ] that can be used to guide clinical diagnosis and treatment. LSCC cells also exhibit complex genomic alterations, including numerous gene mutations and copy number alterations [ 11 ], and are associated with particular biomarkers [ 12 – 14 ] and prognostic factors [ 15 – 17 ].…”