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Multiomics sequencing and immune microenvironment characteristics define three subtypes of small cell neuroendocrine carcinoma of the cervix.
Pan, Baoyue; Yan, Shumei; Yuan, Linjing; Xiang, Huiling; Ju, Mingxiu; Xu, Shijie; Jia, Weihua; Li, Jundong; Zhao, Qi; Zheng, Min.
Afiliación
  • Pan B; Department of Gynecology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
  • Yan S; Department of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
  • Yuan L; Department of Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
  • Xiang H; Department of Gynecology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
  • Ju M; Department of Gynecology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
  • Xu S; Department of Gynecology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
  • Jia W; Biobank of Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
  • Li J; Department of Gynecology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
  • Zhao Q; Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
  • Zheng M; Department of Gynecology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
J Pathol ; 263(3): 372-385, 2024 07.
Article en En | MEDLINE | ID: mdl-38721894
ABSTRACT
Small cell cervical carcinoma (SCCC) is the most common neuroendocrine tumor in the female genital tract, with an unfavorable prognosis and lacking an evidence-based therapeutic approach. Until now, the distinct subtypes and immune characteristics of SCCC combined with genome and transcriptome have not been described. We performed genomic (n = 18), HPV integration (n = 18), and transcriptomic sequencing (n = 19) of SCCC samples. We assessed differences in immune characteristics between SCCC and conventional cervical cancer, and other small cell neuroendocrine carcinomas, through bioinformatics analysis and immunohistochemical assays. We stratified SCCC patients through non-negative matrix factorization and described the characteristics of these distinct types. We further validated it using multiplex immunofluorescence (n = 77) and investigated its clinical prognostic effect. We confirmed a high frequency of PIK3CA and TP53 alterations and HPV18 integrations in SCCC. SCCC and other small cell carcinoma had similar expression signatures and immune cell infiltration patterns. Comparing patients with SCCC to those with conventional cervical cancer, the former presented immune excluded or 'desert' infiltration. The number of CD8+ cells in the invasion margin of SCCC patients predicted favorable clinical outcomes. We identified three transcriptome subtypes an inflamed phenotype with high-level expression of genes related to the MHC-II complex (CD74) and IFN-α/ß (SCCC-I), and two neuroendocrine subtypes with high-level expression of ASCL1 or NEUROD1, respectively. Combined with multiple technologies, we found that the neuroendocrine groups had more TP53 mutations and SCCC-I had more PIK3CA mutations. Multiplex immunofluorescence validated these subtypes and SCCC-I was an independent prognostic factor of overall survival. These results provide insights into SCCC tumor heterogeneity and potential therapies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias del Cuello Uterino / Carcinoma Neuroendocrino / Microambiente Tumoral Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: J Pathol Año: 2024 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias del Cuello Uterino / Carcinoma Neuroendocrino / Microambiente Tumoral Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: J Pathol Año: 2024 Tipo del documento: Article