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Anti–PD-1 Response and Noncoding RNAs in Squamous Cell Skin Cancer

By: Vanessa A. Carter, BS
Posted: Monday, May 20, 2024

Despite the marked success of the anti–PD-1 checkpoint inhibitor cemiplimab-rwlc in patients with cutaneous squamous cell carcinoma, Stefania Tommasi, PhD, of the IRCCS Istituto Tumori “Giovanni Paolo II,” Bari, Italy, and colleagues suggest there is further research to be done on the use of biomarkers in predicting treatment response. Since the essential roles of noncoding RNAs such as microRNAs (miRNAs) and long noncoding RNAs (lncRNA) have come to light, these researchers aimed to assess the lncRNA-miRNA–messenger RNA (mRNA) networks that may correlate with anti–PD-1 response. The results of this study, which highlight the inverse relationship between miR-148a/b and lnc (PVT1 and LINC00665), were presented during the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract 5172/13). A longitudinal study to evaluate miRNA expression and cemiplimab response is ongoing. 

GSE139505 RNA-sequencing raw data, including seven healthy samples and nine cutaneous squamous cell carcinoma biopsies, were retrieved from the Sequence Read Archive (SRA) for the in silico study. LncRNAs and coding genes were used to prepare two matrices. Gene set enrichment analysis was performed using normalized coding gene matrices; coexpression analysis between core enrichment genes and lncRNAs were performed using these data.

In pretherapy plasma samples of 34 patients with cutaneous squamous cell carcinoma, identified miRNAs (miR-125a, miR-125b, miR-148a, miR-148b) and lncRNAs (AF131217.1, RP11-362F19.1, PVT1, LINC00665) were quantified and categorized according to their therapeutic response to cemiplimab.

More than 600 correlations between gene-miRNA-lncRNA networks were identified during coexpression analysis. CD274/HLA-A with mir-148a/b, PVT1/ LINC00665, JUN with mir-125a/b, and AF131217.1/RP11-362F19.1 strongly correlated with the WP_Cancer_Immunotherapy_by_PD1_blockade, whereas CD4-miR-125a/b and AF131217.1/RP11-362F19.1 was associated with the Reactome_PD1_signaling gene set. Overall, there was a significant interaction between mir-148a/b and PVT1/LINC00665 in miRNAs among squamous cell carcinoma samples that responded to anti–PD-1 therapy.

Disclosure: The study authors reported no conflicts of interest.


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