Single-cell RNA sequencing reveals the unique tumor microenvironment of small cell neuroendocrine carcinoma of the ovary

Small cell neuroendocrine carcinoma of the ovary (SCNECO) is a rare and highly ​aggressive malignancy characterized by early metastasis, high recurrence rates, and poor prognosis. Here, we present a single-case, detailed single-cell transcriptomic profiling of this cancer, which remains largely unexplored at this resolution. Our gene regulatory network analysis suggested that high HOXB2 expression correlates with unfavorable patient outcomes. HOXB2 was markedly upregulated during the later stages of neuroendocrine carcinoma progression and was associated with the maintenance of the neuroendocrine phenotype in our data. Furthermore, our data are consistent with the possibility that the neuroendocrine marker genes and their associated regulatory networks in SCNECO differ from those in pulmonary neuroendocrine carcinomas as documented in the Gene Expression Omnibus (GEO) database, supporting a tissue-specific origin for these malignancies, which remains to be confirmed in larger, independent cohorts. Collectively, this work addresses a critical gap in the understanding of SCNECO and provides preliminary, hypothesis-generating insights that may guide future studies on chemotherapy, targeted therapy, and immunotherapy approaches.