Catholic University of Korea, Bucheon, Korea, Republic of (South)
Guk Jin Lee , Jin-Hyoung Kang , In Sook Woo , Ho Jung An , Heejung Lee
Background: Thymic epithelial tumors (TET) are consisted of thymoma(TM) and thymic carcinoma(TC). They are rare heterogeneous tumors with a broad spectrum of clinical characteristics. Although the investigations for potential markers provided some insights into the molecular biology of TET, still there is no established target and biomarker. Methods: We performed the gene microarray related to Insulin-like growth factor-1 receptor (IGF-1R) pathway in the fresh tissues (6 TMs and 5 TCs), and validated the analyzed data of expression profile with quantitative measurement of IGF1, IGF2, IGF1R, INSR, SOX2, and OCT-4 mRNA transcripts using RT-PCR. With the tumor tissues collected from 140 TET patients, we constructed the tissue microarray and did immunohistochemistry (IHC) for IGF-1R signaling-related molecules including SOX2, IGF1R, IGF-1, and pAKT. Results: The mRNA expressions of SOX2 (216 folds) and IGF-1 (5.2 folds) were notably higher in fresh tumor tissue from TC patients than TM, but no significant differences of IGF-1R, Oct-4, and INSR were found between two tumors. Among 140 TET cases, 111 cases were TM, and 29 cases were TC. The expression level of SOX2 (HR 7.57, P= 0.001) and IGF-1 (HR = 9.43, P= 0.001) were significantly higher in TC than TM. With analyzing intermolecular correlation between each molecule, there was statistically significant implications between SOX2 and IGF-1, SOX2 and pAKT (P = 0.021, P = 0.026). In univariate analysis, LDH, clinical TNM staging, WHO classification, SOX2, IGF-1R, IGF-1, and pAKT expression were significantly correlated with overall survival (OS). By multivariate analysis using forward-selection procedure, not only clinical N staging and M staging, but also positive expression of SOX2 and IGF-1 (HR 4.48, P = 0.001) were strongly correlated with OS. Conclusions: Taken together, our study shows that there are great differences between SOX2 and IGF-1 expressions between thymoma and thymic carcinoma. In thymic epithelial tumors, the expression of SOX2 has a strong relation to IGF-1 expression and their higher expressions are significantly associated with shorter overall survival and more aggressive tumor behavior.
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