Clinical Significance of Gli-1 And Caveolin-1 Expression in the Human Small Cell Lung Cancer

Abstract

Background: Lung cancer is the leading causes of cancer-related deaths around the world. Abnormal activation of the hedgehog (Hh) signaling pathway has been found to be involved in the occurrence, invasion, and metastasis of cancers. Autophagy also plays a significant role in the growth and metastasis of cancers. However, the correlation between the Hh signaling pathway and autophagy in small cell lung cancer (SCLC) is still poorly understood. This study aimed to investigate the significance of Hh signaling pathway and autophagy in SCLC. Materials and Methods: The expression of the Hh-induced transcriptional factor, glioma associated oncogene-1 (Gli-1) and the autophagy-related molecule caveolin-1 (Cav-1) and their clinical significance was performed to detect and assay by immunohistochemistry in tissue microarray including 70 patients with SCLC. Results: In our study, 47 (67.1%) patients had positive Gli-1 expression, 49 (70.0%) patients had positive Cav-1 expression, and 44 (62.9%) patients had negative fibroblastic Cav-1 expression. In SCLC, Gli-1 expression increased markedly, and was closely associated with decreased fibroblastic Cav-1 expression. Furthermore, we also found that Gli-1 expression was closely associated with increased Cav-1 expression. Conclusions: Our findings suggested that abnormal activation of the Hh signaling pathway is closely related to autophagy in SCLC. We envision that novel targets may come with the further investigation of Gli-1 and Cav-1 in carcinogenesis of SCLC.

Keywords: Small cell lung cancer; Gli−1; caveolin−1; hedgehog pathway; autophagy.

Figure 1

Gli-1 Protein Expression in SCLC Tissues: A, B, Gli-1 positive expression in SCLC tissues; C, D, weak Gli-1 expression in SCLC tissues; E, F, Gli-1 positive expression in SCLC tissues with low or negative Gli-1 expression in the stromal fibroblasts of SCLC or inflammatory cells (A, C, 100×magnification; B, D, 200×magnification; E, F, 400×magnification).

Figure 2

Cav-1 Protein Expression in SCLC Tissues: A, B, Cav-1 negative stromal fibroblasts of SCLC; C, D, Cav-1 positive expression in stromal fibroblasts of SCLC; E, Cav-1 positive expression in SCLC tissues with negative expression in stromal fibroblasts; F, Cav-1 positive expression on the cell membrane of SCLC tissues (A, C, 100×magnification; B, D, 200×magnification; E, F, 400×magnification).