PATZ1 in Non-Small Cell Lung Cancer: A New Biomarker That Negatively Correlates with PD-L1 Expression and Suppresses the Malignant Phenotype

Abstract

Non-small cell lung cancer (NSCLC), the leading cause of cancer death worldwide, is still an unmet medical problem due to the lack of both effective therapies against advanced stages and markers to allow a diagnosis of the disease at early stages before its progression. Immunotherapy targeting the PD-1/PD-L1 checkpoint is promising for many cancers, including NSCLC, but its success depends on the tumor expression of PD-L1. PATZ1 is an emerging cancer-related transcriptional regulator and diagnostic/prognostic biomarker in different malignant tumors, but its role in lung cancer is still obscure. Here we investigated expression and role of PATZ1 in NSCLC, in correlation with NSCLC subtypes and PD-L1 expression. A cohort of 104 NSCLCs, including lung squamous cell carcinomas (LUSCs) and adenocarcinomas (LUADs), was retrospectively analyzed by immunohistochemistry for the expression of PATZ1 and PD-L1. The results were correlated with each other and with the clinical characteristics, showing on the one hand a positive correlation between the high expression of PATZ1 and the LUSC subtype and, on the other hand, a negative correlation between PATZ1 and PD-L1, validated at the mRNA level in independent NSCLC datasets. Consistently, two NSCLC cell lines transfected with a PATZ1-overexpressing plasmid showed PD-L1 downregulation, suggesting a role for PATZ1 in the negative regulation of PD-L1. We also showed that PATZ1 overexpression inhibits NSCLC cell proliferation, migration, and invasion, and that Patz1-knockout mice develop LUAD. Overall, this suggests that PATZ1 may act as a tumor suppressor in NSCLC.

Immunotherapy in thymic epithelial tumors: tissue predictive biomarkers for immune checkpoint inhibitors

“…The efficacy of ICIs can be predicted by the evaluation of appropriate biomarkers of therapy response [ 38 ]. The level of PD-L1 expression in tumor cells and TMB are established as predictive biomarkers of therapeutic response in many solid tumors [ 19 , 39 , 40 ]. Recently, investigative efforts have been underway to identify predictive biomarkers of response to ICIs in TETs [ 41 ].…”

Multidisciplinary Approach to the Diagnosis of Idiopathic Interstitial Pneumonias: Focus on the Pathologist’s Key Role

“…The clinical consequence is impaired gas exchange, resulting in breathlessness, diminished exercise tolerance, and impairment of lung function and quality of life [3]. Unlike neoplastic lung disease [4,5], inflammatory lung disease is often a source of great diagnostic difficulties for pathologists. Nonetheless, a precise diagnosis is essential because the prognosis and course of treatment differ greatly amongst ILDs.…”