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

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...

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Bibliographic Details
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
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Summary: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

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