Xinyi Chen

Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age

Clinicopathologic characteristics and survival outcomes of patients with high-grade neuroendocrine cervical cancer

This study aims to evaluate the clinicopathologic characteristics and survival of patients with high-grade neuroendocrine cervical cancer in a consecutive cohort from a single center. We retrospectively reviewed clinical data of cervical cancer patients admitted to our hospital between 2010 and 2023. The clinicopathologic and immunohistochemical features and treatment outcomes were summarized. Progression-free survival (PFS) and overall survival (OS) were estimated using a Cox proportional hazards regression model. A total of 5782 patients with cervical cancer were treated in our hospital; 54 (0.93%) of these patients were diagnosed with high-grade neuroendocrine carcinoma. Compared with patients with other histological subtypes, patients with high-grade neuroendocrine cervical cancer were significantly more likely to be diagnosed before 40 years of age ( P  = .043). The 5-year PFS rate was 65.6% (95% confidence interval [CI]: 55.4–75.8%) for stage I disease, dropping markedly to 19.3% (95% CI: 7.9–30.7%) for stages II–III. Similarly, the 5-year OS rate was 69.0% (95% CI: 59.0–79.0%) for stage I, compared with 23.9% (95% CI: 10.0–37.8%) for stages II–IV. According to multivariate analyses, patients with lymph node involvement exhibited significantly worse PFS (adjusted hazard ratio = 7.26; 95% CI: 1.62–32.61; P  < .01) and OS (adjusted hazard ratio = 7.98; 95% CI: 1.82–34.87; P  < .01) than patients without lymph node involvement. High-grade neuroendocrine cervical carcinoma is a rare and aggressive malignancy whose prognosis is critically dependent on the International Federation of Gynecology and Obstetrics stage. Early diagnosis, achievable through regular human papillomavirus screening followed by systematic colposcopy and biopsy, is important. Furthermore, comprehensive molecular profiling of mutations and the transcriptome is essential to inform personalized management strategies.

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

ABSTRACTSmall‐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.