Single-Cell RNA Sequencing Reveals the Cellular Origin and Evolution of Small-Cell Neuroendocrine Carcinoma of the Cervix

被引：0

作者：

Chen, Xinyi ^{[1
]}

Wang, Kunyu ^{[2
]}

Liao, Xingyu ^{[3
]}

Zheng, Xingzheng ^{[4
]}

Yang, Shuli ^{[5
]}

Han, Chao ^{[1
]}

Lu, Chang ^{[1
]}

Wang, Xiaodan ^{[1
]}

Jin, Lingge ^{[1
]}

Kang, Haili ^{[5
]}

Han, Yiding ^{[4
]}

Wei, Jiacong ^{[6
]}

Fan, Linyuan ^{[1
]}

Zhang, Zhan ^{[1
]}

Kong, Weimin ^{[1
]}

机构：

[1] Capital Med Univ, Beijing Obstet & Gynecol Hosp, Beijing Maternal & Child Hlth Care Hosp, Dept Gynecol, Beijing, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Dept Gynecol Oncol, Natl Clin Res Ctr Canc,Canc Hosp, Beijing, Peoples R China

[3] Peking Univ Canc Hosp & Inst, Minist Educ Beijing, Familial & Hereditary Canc Ctr, Key Lab Carcinogenesis & Translat Res, R China, Beijing, Peoples R China

[4] Capital Med Univ, Beijing Obstet & Gynecol Hosp, Beijing Maternal & Child Hlth Care Hosp, Dept Pathol, Beijing, Peoples R China

[5] Capital Med Univ, Beijing Obstet & Gynecol Hosp, Beijing Maternal & Child Hlth Care Hosp, Dept Gynecol Oncol, Beijing, Peoples R China

[6] Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Dept Pathol, Natl Clin Res Ctr Canc,Canc Hosp, Beijing, Peoples R China

来源：

JOURNAL OF MEDICAL VIROLOGY | 2025年 / 97卷 / 01期

基金：

中国国家自然科学基金;

关键词：

cervical cancer; HPV; single-cell RNA sequencing; small-cell neuroendocrine cancer; SOX2; LINEAGE PLASTICITY; CANCER; DRIVES; SOX2;

D O I：

10.1002/jmv.70183

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Small-cell neuroendocrine cancer (SCNEC) of the uterine cervix is an exceedingly rare, highly aggressive tumor with an extremely poor prognosis. The cellular heterogeneity, origin, and tumorigenesis trajectories of SCNEC of the cervix remain largely unclear. We performed single-cell RNA sequencing and whole-exome sequencing on tumor tissues and adjacent normal cervical tissues from two patients diagnosed with SCNEC of the cervix. Here, we provide the first comprehensive insights into the cellular composition, HPV infection-related features, and gene expression profiles of SCNEC of the cervix at single-cell resolution. Correlation analyses suggested that SCNEC of the cervix may originate from squamous epithelial cells, and this observation was validated with bulk RNA-seq data from external cervical neuroendocrine cancer. Furthermore, sex-determining region Y-box 2 (SOX2), a key transcription factor that functions in direct neural differentiation, was located in the copy number gain region and highly expressed in neuroendocrine tumor cells from both patients. Notable, the distributions of the HPV-infected epithelium and SOX2 highly expressed epithelium were consistent with each other. Therefore, we supposed that high-risk HPV infection and amplification of SOX2 in the squamous epithelium may contribute to the progression of small-cell neuroendocrine tumorigenesis in the cervix.

引用

页数：12