Table 1 Characteristics of the lung SCC patients (Tianjin cohort)

Table 1 Characteristics of the lung SCC patients (Tianjin cohort)

Characteristics No Percent Age (Years)     <60 71 40.1% ≥60 106 59.9% Gender     Male 151 85.3% Female 26 #CP673451 concentration randurls[1|1|,|CHEM1|]# 14.7% Smoking history     Never 29 16.4% Smoker 148 83.6% Surgical Procedure     Lobectomy 143 80.8% Pneumonectomy 30 16.9% Extend 4 2.3% T stage     T1 45 25.4% T2 107 60.5% T3 25 14.1% N stage     N0 126 71.2% N1 16 9.0% N2 35 19.8% TNM Stage     I 91 51.4% II 48 27.1% IIIA 38 21.5% Next we analyzed the association between expressions of key components in the Shh pathway. Kendall’s tau-b correlation tests yielded significant correlations between every two factors (p = 0.000), while Kappa’s test suggested strong positive association between SHh and Gli1(p = 0.000) (Figure 1C), suggesting the canonical Shh pathway is activated in lung SCC. These data are consistent with previous reports that the upstream Shh signaling has correlations with downstream targets in NSCLC [29, 30]. Taken together, our results suggest that aberrant activation of the Shh pathway plays an important role in lung SCC. Gli expression reversely correlates with EMT markers E-Cadherin is a well-established GSK2126458 order EMT biomarker, and its expression

has been suggested to be associated with cancer recurrence and metastasis [5]. The expression of β-Catenin also serves as a biomarker for EMT [31]. To investigate whether the Shh/Gli signaling plays a role in EMT regulation in lung SCC, we first examined 14 lung SCC patients who underwent surgical resection for lung SCC at the Thoracic Oncology Program at UCSF. Eight of fourteen samples showed reverse correlation between E-Cadherin and Gli1 expressions (three representative samples were shown in Figure 2A). To confirm the reverse correlation between EMT markers and Gli1 expressions in lung SCC, we further analyzed E-Cadherin and β-Catenin

expressions and correlated with Gli1 mTOR inhibitor expression in the Tianjin cohort. Our results revealed strong reverse correlations between Gli1 and E-Cadherin (p = 0.003), as well as Gli1 and β-Catenin (p = 0.004) (Figures 2B and C). We also observed reverse correlation between Gli1 and E-Cadherin expression at different areas within one sample in multiple cases due to the heterogeneity of tumor cells (Figure 2), further supporting the reverse correlation between Gli1 and EMT marker expressions. Moreover, our analysis revealed that Gli1 significantly correlated with recurrence and metastasis of lung SCC in the Tianjin cohort (p = 0.033; Figure 2C). Consistent with the tissue expression analysis, we observed that Gli1 expression reversely correlated with E-Cadherin expression in four human lung SCC cell lines, H1703, H1869, H2170 and SK-MES-1 (Figure 2D). Taken together, our results indicate the essential role of Gli1, a downstream effector of Shh pathway, in enhancing EMT, which in turn promotes recurrence and metastasis in lung SCC.

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