Open AccessAbstract 3192: PD-L1 is an independent prognostic marker in Middle Eastern PTC and its expression is upregulated by BRAFV600E mutation
Author(s) -
Tariq Masoodi,
Abdul K. Siraj,
Sandeep Kumar Parvathareddy,
Poyil Pratheeshkumar,
S. Divya,
Rafia Begum,
Roxanne Diaz,
Saravanan Thangavel,
Khadija Alobaisi,
Sarah Siraj,
Saud Azam,
Zeeshan Qadri,
Khawla S. AlKuraya
Publication year - 2021
Publication title -
cancer research
Language(s) - English
Resource type - Conference proceedings
SCImago Journal Rank - 1.055
H-Index - 84
eISSN - 1538-7445
pISSN - 0008-5472
DOI - 10.1158/1538-7445.am2021-3192
Subject(s) - cancer research , vemurafenib , gene knockdown , mutation , immunohistochemistry , cell culture , medicine , cell growth , cell , oncology , biology , melanoma , gene , genetics , metastatic melanoma
Background: PD-L1 inhibition is a promising therapeutic target whose efficacy has been demonstrated in several cancers. This study was conducted to evaluate the prognostic significance of PD-L1 expression in a large cohort of Middle Eastern PTC patients and to explore correlation of PD-L1 and BRAFV600E mutations in PTC tumors and cell lines. Methods: 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. Results: PD-L1 over-expression was noted in 32.4% (473/1458) of cases and significantly associated with adverse clinico-pathological parameters such as tall cell variant, extra-thyroidal extension and lymph node metastasis. 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 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. Conclusion: Our data suggests 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 tall cell variant, BRAF mutation positive patients that are unresponsive to standard treatment. Citation Format: Tariq Masoodi, Abdul K. Siraj, Sandeep Kumar Parvathareddy, Poyil Pratheeshkumar, Sasidharan Padmaja Divya, Rafia Begum, Roxanne Diaz, Thangavel Saravanan, Khadija Al-Obaisi, Sarah Siraj, Saud Azam, Zeeshan Qadri, Khawla S. Al-Kuraya. PD-L1 is an independent prognostic marker in Middle Eastern PTC and its expression is upregulated by BRAFV600E mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3192.