The expression of SALL4 is significantly associated with EGFR, but not KRAS or EML4-ALK mutations in lung cancer

J Thorac Dis. 2016 Oct;8(10):2682-2688. doi: 10.21037/jtd.2016.09.64.

Abstract

Background: Lung cancer is the leading cause of cancer-related deaths worldwide; unfortunately, its prognosis is still very poor. Therefore, developing the target molecular is very important for lung cancer diagnosis and treatment, especially in the early stage. With this in view, spalt-like transcription factor 4 (SALL4) is considered a potential biomarker for diagnosis and prognosis in cancers, including lung cancer.

Methods: In order to better investigate the association between the expression of SALL4 and driver genes mutation, 450 histopathologically diagnosed patients with lung cancer and 11 non-cancer patients were enrolled to test the expression of SALL4 and the status of driver genes mutation. This investigation included epidermal growth factor receptor (EGFR), kirsten rat sarcoma viral oncogene homolog (KRAS), and a fusion gene of the echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK).

Results: The results of the study showed that females harbored more EGFR mutation in adenocarcinoma (ADC). The mutation rate of KRAS and EML4-ALK was about 5%, and the double mutations of EGFR/EML4-ALK were higher than EGFR/KRAS. In the expression analysis, the expression of SALL4 was much higher in cancer tissues than normally expected, especially in tissues that carried EGFR mutation (P<0.05), however, there were no significant differences between different mutation types. Likewise, there were no significant differences between expression of SALL4 and KRAS and EML4-ALK mutations.

Conclusions: SALL4 is up regulated in lung cancer specimens and harbors EGFR mutation; this finding indicates that SALL4 expression may be relevant with EGFR, which could provide a new insight to lung cancer therapy. The mechanism needs further investigation and analysis.

Keywords: EML4-ALK; Epidermal growth factor receptor (EGFR); SALL4 expression; kirsten rat sarcoma viral oncogene homolog (KRAS); lung cancer.