Oncogenic Transformation from Actinic Cheilosis to Squamous Cell Carcinoma of the Lip

Lip is an anatomical junction between skin and mucosa and the squamous cell carcinoma (SCC) is the most frequent lip cancers. Lip SCC is frequently developed from actinic cheilitis, presented as ulcerative lesions. However, changes in transcriptomes and tumor microenvironment driving oncogenic transformation from actinic cheilitis to lip SCC and determinants of differentiation of lip SCC are largely unknown. This study aimed to investigate differences between lip SCC and its premalignant actinic cheilitis and factors related to tumor differentiation. Overall design: We selected patients who received biopsies for actinic cheilitis which progressed to lip SCC several years later. In addition, biopsy samples of well-differentiated lip SCC and moderately- to poorly-differentiated lip SCC were used for spatial transcriptomic analysis. PanCK and CD45 were used as morphology markers and a total of 60 regions of interest (ROIs) were selected.