Siraj, Abdul K. and Parvathareddy, Sandeep Kumar and Pratheeshkumar, Poyil and Divya, Sasidharan Padmaja and Al-Sobhi, Saif S. and Al-Dayel, Fouad and Al-Kuraya, Khawla S. (2021) PD-L1 Is an Independent Prognostic Marker in Middle Eastern PTC and Its Expression Is Upregulated by BRAFV600E Mutation. Cancers, 13 (3). p. 555. ISSN 2072-6694
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Abstract
PD-L1 inhibition is a promising therapeutic target whose efficacy has been demonstrated in several cancers. Immunohistochemistry was performed to assess PD-L1 protein expression in PTC. We further conducted in vitro analysis to investigate the role of PD-L1 in regulating BRAFV600E in PTC cell lines. PD-L1 over-expression was noted in 32.4% (473/1458) of cases and significantly associated with aggressive clinico-pathological parameters. Importantly, PD-L1 was found to be an independent poorer prognostic marker. We also found PD-L1 to be significantly associated with BRAF mutation and patients with co-existing PD-L1 over-expression and BRAF mutation had a poor disease-free survival compared to patients with BRAF mutation alone. In vitro analysis showed high expression of PD-L1 in BRAF-mutated PTC cell lines compared to a BRAF wild-type cell line. Inhibition of BRAF using vemurafenib induced PD-L1 expression in BRAF-mutated cell lines without affecting cell growth. Knockdown of PD-L1 in BRAF-mutated cell lines significantly decreased the cell growth and induced apoptosis. Our data suggest that PD-L1 might represent a useful prognostic marker in Middle Eastern PTC and PD-L1 inhibition could be a potential therapeutic option for aggressive PTC cancers, such as the tall cell variant, BRAF mutation-positive patients that are unresponsive to standard treatment.
Item Type: | Article |
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Subjects: | STM Digital Library > Medical Science |
Depositing User: | Unnamed user with email support@stmdigitallib.com |
Date Deposited: | 07 Jan 2023 09:45 |
Last Modified: | 20 Jun 2024 13:21 |
URI: | http://archive.scholarstm.com/id/eprint/100 |