Transcription factor PAX6 as a novel prognostic factor and putative tumour suppressor in non-small cell lung cancer

• Published in: Scientific Reports
• Main Authors: Kiselev, Yury, Andersen, Sigve, Johannessen, Charles, Fjukstad, Bjørn, Olsen, Karina Standahl, Stenvold, Helge, Al-Saad, Samer, Dønnem, Tom, Richardsen, Elin, Bremnes, Roy M., Busund, Lill-Tove
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Research 2019
• Subjects: Lung cancer; Cancer deaths; Predictive biomarkers; Prognostic markers; Cancer treatment; Anchorage; Arctic; Norway; Arctic University of Norway; UiT The Arctic University of Norway
• Online Access: https://hdl.handle.net/10642/6677; https://doi.org/10.1038/s41598-018-23417-z

Lung cancer is the leading cause of cancer deaths. Novel predictive biomarkers are needed to improve treatment selection and more accurate prognostication. PAX6 is a transcription factor with a proposed tumour suppressor function. Immunohistochemical staining was performed on tissue microarrays from 335 non-small cell lung cancer (NSCLC) patients for PAX6. Multivariate analyses of clinico-pathological variables and disease-specific survival (DSS) was carried out, and phenotypic changes of two NSCLC cell lines with knockdown of PAX6 were characterized. While PAX6 expression was only associated with a trend of better disease-specific survival (DSS) (p = 0.10), the pN+ subgroup (N = 103) showed significant correlation between high PAX6 expression and longer DSS (p = 0.022). Median survival for pN + patients with high PAX6 expression was 127.4 months, versus 22.9 months for patients with low PAX6 expression. In NCI-H661 cells, knockdown of PAX6 strongly activated serum-stimulated migration. In NCI-H460 cells, PAX6 knockdown activated anchorage-independent growth. We did not observe any significant effect of PAX6 on proliferation in either of cell lines. Our findings strongly support the proposition of PAX6 as a valid and positive prognostic marker in NSCLC in node-positive patients. There is a need for further studies, which should provide mechanistical explanation for the role of PAX6 in NSCLC. This study was supported by a grant to Y.K. from Helse Nord (The Northern Norwegian Health Administration). The publication charges for this article have been funded by a grant from the publication fund of UiT The Arctic University of Norway. publishedVersion