Correlation of PD-L1 and HIF-1 Alpha Expression with KRAS Mutation and Clinicopathological Parameters in Non-Small Cell Lung Cancer

<b>Background:</b> Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung carcinomas (NSCLCs) comprising the majority of cases. Among the common driver mutations, KRAS plays a critical role in guiding treatment strategies. This study evaluates...

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Main Authors: Seda Er Özilhan, Safa Can Efil, Doğukan Çanakçı, Yetkin Ağaçkıran, Didem Şener Dede, Nilüfer Onak Kandemir, Mehmet Doğan, Tuba Dilay Kökenek Ünal, Merve Meryem Kıran, Serra Kayaçetin, Hilal Balta, Hayriye Tatlı Doğan
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/47/2/121
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Summary:<b>Background:</b> Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung carcinomas (NSCLCs) comprising the majority of cases. Among the common driver mutations, KRAS plays a critical role in guiding treatment strategies. This study evaluates the expression of programmed death-ligand 1 (PD-L1) and hypoxia-inducible factor 1-alpha (HIF-1α) in <i>KRAS</i>-mutant NSCLCs and investigates their associations with clinicopathological findings. <b>Methods:</b> A total of 85 cases with <i>KRAS</i> mutations were analyzed. Immunohistochemical staining for HIF-1α and PD-L1 was performed, and their relationships with mutation status and prognostic variables were assessed. <b>Results:</b> A significant correlation was identified between HIF-1α expression and PD-L1 expression in tumor cells. While the <i>KRAS</i> G12C mutation was not significantly associated with HIF-1α expression in tumor cells, it demonstrated a notable relationship with HIF-1α expression in the tumor microenvironment and PD-L1 expression. However, PD-L1 and HIF-1α expression did not significantly influence overall survival outcomes. <b>Conclusions:</b> Expression of PD-L1 was positively correlated with HIF-1α, which may provide evidence for a novel therapy targeting PD-L1 and HIF-1α in NSCLC. Further comprehensive studies are warranted to elucidate the prognostic implications of tumor–microenvironment and mutation interactions.
ISSN:1467-3037
1467-3045