Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Yunnan, China; Department of Dermatology, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China
Ya-Zhou Sun
Clinical Big Data Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China; School of Medical, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China
Xin-Jie Li
School of Medical, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China
Wen-Juan Wu
Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Yunnan, China
Dan Xu
Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Yunnan, China
Yu-Tong He
School of Medical, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China
Jue Qi
Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Yunnan, China
Ying Tu
Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Yunnan, China
Yang Tang
Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Yunnan, China
Yun-Hua Tu
Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Yunnan, China
Xiao-Li Wang
Department of Dermatology, Changzheng Hospital, Naval Medical University, Shanghai, China
Xing Li
Department of Dermatology, People's Hospital of Chuxiong Yi Autonomous Prefecture, Chuxiong, Yunnan, China
Feng-Yan Lu
Department of Dermatology, Qujing Affiliated Hospital of Kunming Medical University, The First People’s Hospital of Qujing, Yunnan, China
Ling Huang
Department of Dermatology, First Affiliated Hospital of Dali University, Dali, Yunnan, China
Heng Long
Wenshan Zhuang and Miao Autonomous Prefecture Dermatology Clinic, Wenshan Zhuang and Miao Autonomous Prefecture Specialist Hospital of Dermatology, Wenshan, Yunnan, China
School of Medical, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Guangdong, China
Cutaneous squamous cell carcinoma (cSCC) is the second most frequent of the keratinocyte-derived malignancies with actinic keratosis (AK) as a precancerous lesion. To comprehensively delineate the underlying mechanisms for the whole progression from normal skin to AK to invasive cSCC, we performed single-cell RNA sequencing (scRNA-seq) to acquire the transcriptomes of 138,982 cells from 13 samples of six patients including AK, squamous cell carcinoma in situ (SCCIS), cSCC, and their matched normal tissues, covering comprehensive clinical courses of cSCC. We identified diverse cell types, including important subtypes with different gene expression profiles and functions in major keratinocytes. In SCCIS, we discovered the malignant subtypes of basal cells with differential proliferative and migration potential. Differentially expressed genes (DEGs) analysis screened out multiple key driver genes including transcription factors along AK to cSCC progression. Immunohistochemistry (IHC)/immunofluorescence (IF) experiments and single-cell ATAC sequencing (scATAC-seq) data verified the expression changes of these genes. The functional experiments confirmed the important roles of these genes in regulating cell proliferation, apoptosis, migration, and invasion in cSCC tumor. Furthermore, we comprehensively described the tumor microenvironment (TME) landscape and potential keratinocyte-TME crosstalk in cSCC providing theoretical basis for immunotherapy. Together, our findings provide a valuable resource for deciphering the progression from AK to cSCC and identifying potential targets for anticancer treatment of cSCC.
