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Distinct transcriptomic landscapes of cutaneous basal cell carcinomas and squamous cell carcinomas.

ABSTRACT: The majority of non-melanoma skin cancer (NMSC) is cutaneous basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), which are also called keratinocyte carcinomas, as both of them originate from keratinocytes. The incidence of keratinocyte carcinomas is over 5 million per year in the US, three-fold higher than the total incidence of all other types of cancer combined. While there are several reports on gene expression profiling of BCC and SCC, there are significant variations in the reported gene expression changes in different studies. One reason is that tumor-adjacent normal skin specimens were not included in many studies as matched controls. Furthermore, while numerous studies of skin stem cells in mouse models have been reported, their relevance to human skin cancer remains unknown. In this report, we analyzed gene expression profiles of paired specimens of keratinocyte carcinomas with their matched normal skin tissues as the control. Among several novel findings, we discovered a significant number of zinc finger encoding genes up-regulated in human BCC. In BCC, a novel link was found between hedgehog signaling, Wnt signaling, and the cilium. While the SCC cancer-stem-cell gene signature is shared between human and mouse SCCs, the hair follicle stem-cell signature of mice was not highly represented in human SCC. Differential gene expression (DEG) in human BCC shares gene signature with both bulge and epidermal stem cells. We have also determined that human BCCs and SCCs have distinct gene expression patterns, and some of them are not fully reflected in current mouse models.

SUBMITTER: Wan J

PROVIDER: S-EPMC8099692 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceDefining which populations are affected by basal cell carcinoma (BCC) vs cutaneous squamous cell carcinoma (cSCC) may inform targeted public health strategies. Incidence of BCC and cSCC is not reported to national cancer registries, but claims data for the treatment of BCC and cSCC provide insights into the epidemiology of keratinocyte carcinoma.ObjectiveTo define differences in the ratio of BCC to cSCC in adults (age, ≥18 years) in a large database of patients with commercial insurance and Medicare Advantage coverage.Design, setting, and participantsThis cross-sectional analysis used deidentified data derived from the Optum Clinformatics Data Mart to perform a retrospective evaluation of a large commercially insured cohort based on treatment claims from January 1, 2012, to December 31, 2016. Patients with a diagnosed and treated BCC or cSCC as determined by codes from the International Classification of Diseases, Ninth Revision, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, and Current Procedural Terminology were included. Data were analyzed from November 30, 2019, to March 20, 2020.ExposureDiagnosis and treatment of BCC or cSCC.Main outcomes and measuresThe ratio of BCC to cSCC based on age, sex, race, and geographic location. Multivariable logistic regression was used to assess how demographics were associated with the odds of a treated keratinocyte carcinoma being a BCC.ResultsAmong the 985 317 claims for patients included in the analysis (61.59% for men; mean [SD] age, 69.82 [12.58] years), BCCs were 1.69 (95% CI, 1.6899-1.6901) times more likely than cSCCs to be treated in the United States from 2012 to 2016. Basal cell carcinomas were significantly more prevalent than cSCCs in younger patients (18-39 years, 9.63 [95% CI, 9.6088-9.6574] BCCs per cSCC; 40-64 years, 2.92 [95% CI, 2.9171-2.9187] BCCs per cSCC; and ≥65 years, 1.33 [95% CI, 1.3289-1.3291] BCCs per cSCC; P < .001). Basal cell carcinomas were significantly more prevalent than cSCCs in women vs men, except in adults 65 years or older (odds ratios [ORs], 0.98 [95% CI, 0.97-0.99] vs 1.67 [95% CI, 1.47-1.88] for those aged 18-39 and 1.15 [95% CI, 1.12-1.19] for those aged 40-64 years; P < .001). The difference in BCC:cSCC ratios between men and women diminished with increasing age (OR, 1.67 for 18-39 years, 1.15 for 40-64 years, and 0.98 for 65 years or older). Basal cell carcinoma was more prevalent than cSCC in all races, including Black patients (BCC:SCC ratios, 1.60 for Asian patients, 1.45 for Black patients, 2.00 for Hispanic patients, and 1.69 for White patients of all ages). The BCC:cSCC ratio varied based on geography, with the highest ratio in the West North Central census division (2.12) and the lowest ratio in the South Atlantic census division (1.35).Conclusions and relevanceIn the absence of a national registry, claims data can improve our understanding of the epidemiology of keratinocyte carcinomas. In this cross-sectional study, basal cell carcinomas were more common than cSCCs for all demographics, including in Black patients. In populations younger than 40 years, BCCs were 12.6 times more likely for women and 7.2 times more likely for men. These demographic groups may benefit from public health education focused on the presentation and management of BCCs.

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Distinct transcriptomic landscapes of cutaneous basal cell carcinomas and squamous cell carcinomas.

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