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Soo Park, MD
Soo Park, MD
Posted: Thursday, February 1, 2024
Possible targets for therapeutics have been identified in immunosuppressed patients with cutaneous squamous cell carcinomas, according to an article published in the journal Oral Oncology. “We demonstrate an enrichment in microsatellite instability in the tumors from immunosuppressed patients and differences in oxidative phosphorylation and epithelial-mesenchymal transition,” explained Kristin P. Bibee, MD, PhD, of the University of Pittsburgh School of Medicine, and colleagues.
“There is a great need to improve therapeutic options for immunosuppressed patients, both early by dermatologists and later in more advanced disease by medical oncologists,” the authors commented.
The authors used whole-exome and RNA-sequencing techniques in their study. Both DNA and RNA were extracted from a total of 20 formalin-fixed, paraffin-embedded tumor samples. A total of 14 tumors were derived from patients who were classified as immunosuppressed, and 6 came from patients who were immunocompetent. RNA and DNA from skin adjacent to the tumor samples was also extracted. The group then used gene-set enrichment, motif activity, mutational signature, and variant-calling analysis to assess differences in gene expression between tumor and adjacent tissue samples.
The researchers reported that both immunocompetent and immunosuppressed cohorts revealed similar mutational burden. As the researchers expected, the mutation signature of both cohorts indicated exposure to ultraviolet radiation along with azathioprine. Bioinformatic analysis revealed that half of the tumors from patients with immunosuppression contained mutations consistent with microsatellite instability. However, just 17% of patients with immunocompetency had tumors associated with microsatellite instability. Furthermore, the mutated genes among patients with immunosuppression were associated with the extracellular matrix receptor interaction and calcium signaling pathways. Specifically, the group identified that the transcription factors ATF4, PLAG1, SOX14, and RORA had greater activity within tumors from patients who were immunosuppressed than within tumors from those who were immunocompetent.
Disclosure: The study authors reported no conflicts of interests.
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