Single-Cell Transcriptome Analysis of Small Cell Neuroendocrine Carcinoma of the Endometrium Reveals ISL1 as a Potential Biomarker for Diagnosis and Treatment

Background: As a dedifferentiated tumor, small cell endometrial neuroendocrine tumors (NETs) are rare and frequently diagnosed at an advanced stage with a poor prognosis. Current treatment recommendations are often extrapolated from histologically similar tumors in other sites or based on retrospect...

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Main Authors: Cheng Zhong, Yu-e Guo, Qianlan Yang, Yunfeng Song, Tongshuai Wang, Bailian Cai, Hao Chen, He Du, Jing Wan, Yin Liu, Yiran Li, Xiaoping Wan
Format: Article
Language:English
Published: IMR Press 2024-03-01
Series:Frontiers in Bioscience-Landmark
Subjects:
Online Access:https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903100
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author Cheng Zhong
Yu-e Guo
Qianlan Yang
Yunfeng Song
Tongshuai Wang
Bailian Cai
Hao Chen
He Du
Jing Wan
Yin Liu
Yiran Li
Xiaoping Wan
author_facet Cheng Zhong
Yu-e Guo
Qianlan Yang
Yunfeng Song
Tongshuai Wang
Bailian Cai
Hao Chen
He Du
Jing Wan
Yin Liu
Yiran Li
Xiaoping Wan
author_sort Cheng Zhong
collection DOAJ
description Background: As a dedifferentiated tumor, small cell endometrial neuroendocrine tumors (NETs) are rare and frequently diagnosed at an advanced stage with a poor prognosis. Current treatment recommendations are often extrapolated from histologically similar tumors in other sites or based on retrospective studies. The exploration for diagnostic and therapeutic markers in small cell NETs is of great significance. Methods: In this study, we conducted single-cell RNA sequencing on a specimen obtained from a patient diagnosed with small cell endometrial neuroendocrine carcinoma (SCNEC) based on pathology. We revealed the cell map and intratumoral heterogeneity of the cancer cells through data analysis. Further, we validated the function of ISL LIM Homeobox 1 (ISL1) in vitro in an established neuroendocrine cell line. Finally, we examined the association between ISL1 and tumor staging in small cell lung cancer (SCLC) patient samples. Results: We observed the significant upregulation of ISL1 expression in tumor cells that showed high expression of the neuroepithelial markers. Additionally, in vitro cell function experiments demonstrated that the high ISL1 expression group exhibited markedly higher cell proliferation and migration abilities compared to the low expression group. Finally, we showed that the expression level of ISL1 was correlated with SCLC stages. Conclusions: ISL1 protein in NETs shows promise as a potential biomarker for diagnosis and treatment.
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spelling doaj.art-aaecac26a90142f099fc5edc7998b74d2024-03-28T02:27:54ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-03-0129310010.31083/j.fbl2903100S2768-6701(24)01223-1Single-Cell Transcriptome Analysis of Small Cell Neuroendocrine Carcinoma of the Endometrium Reveals ISL1 as a Potential Biomarker for Diagnosis and TreatmentCheng Zhong0Yu-e Guo1Qianlan Yang2Yunfeng Song3Tongshuai Wang4Bailian Cai5Hao Chen6He Du7Jing Wan8Yin Liu9Yiran Li10Xiaoping Wan11Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaDepartment of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433 Shanghai, ChinaShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaDepartment of Oncology, Shanghai Pulmonary Hospital Affiliated to Tongji University School of Medicine, 200433 Shanghai, ChinaDepartment of Gynecologic Oncology, International Peace Maternity & Child Health Hospital of China Welfare Institute, Shanghai Jiaotong University, 200030 Shanghai, ChinaDepartment of Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433 Shanghai, ChinaShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200120 Shanghai, ChinaBackground: As a dedifferentiated tumor, small cell endometrial neuroendocrine tumors (NETs) are rare and frequently diagnosed at an advanced stage with a poor prognosis. Current treatment recommendations are often extrapolated from histologically similar tumors in other sites or based on retrospective studies. The exploration for diagnostic and therapeutic markers in small cell NETs is of great significance. Methods: In this study, we conducted single-cell RNA sequencing on a specimen obtained from a patient diagnosed with small cell endometrial neuroendocrine carcinoma (SCNEC) based on pathology. We revealed the cell map and intratumoral heterogeneity of the cancer cells through data analysis. Further, we validated the function of ISL LIM Homeobox 1 (ISL1) in vitro in an established neuroendocrine cell line. Finally, we examined the association between ISL1 and tumor staging in small cell lung cancer (SCLC) patient samples. Results: We observed the significant upregulation of ISL1 expression in tumor cells that showed high expression of the neuroepithelial markers. Additionally, in vitro cell function experiments demonstrated that the high ISL1 expression group exhibited markedly higher cell proliferation and migration abilities compared to the low expression group. Finally, we showed that the expression level of ISL1 was correlated with SCLC stages. Conclusions: ISL1 protein in NETs shows promise as a potential biomarker for diagnosis and treatment.https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903100uterine neuroendocrine tumorssingle-cell rna sequencingisl1cell proliferation and migration
spellingShingle Cheng Zhong
Yu-e Guo
Qianlan Yang
Yunfeng Song
Tongshuai Wang
Bailian Cai
Hao Chen
He Du
Jing Wan
Yin Liu
Yiran Li
Xiaoping Wan
Single-Cell Transcriptome Analysis of Small Cell Neuroendocrine Carcinoma of the Endometrium Reveals ISL1 as a Potential Biomarker for Diagnosis and Treatment
Frontiers in Bioscience-Landmark
uterine neuroendocrine tumors
single-cell rna sequencing
isl1
cell proliferation and migration
title Single-Cell Transcriptome Analysis of Small Cell Neuroendocrine Carcinoma of the Endometrium Reveals ISL1 as a Potential Biomarker for Diagnosis and Treatment
title_full Single-Cell Transcriptome Analysis of Small Cell Neuroendocrine Carcinoma of the Endometrium Reveals ISL1 as a Potential Biomarker for Diagnosis and Treatment
title_fullStr Single-Cell Transcriptome Analysis of Small Cell Neuroendocrine Carcinoma of the Endometrium Reveals ISL1 as a Potential Biomarker for Diagnosis and Treatment
title_full_unstemmed Single-Cell Transcriptome Analysis of Small Cell Neuroendocrine Carcinoma of the Endometrium Reveals ISL1 as a Potential Biomarker for Diagnosis and Treatment
title_short Single-Cell Transcriptome Analysis of Small Cell Neuroendocrine Carcinoma of the Endometrium Reveals ISL1 as a Potential Biomarker for Diagnosis and Treatment
title_sort single cell transcriptome analysis of small cell neuroendocrine carcinoma of the endometrium reveals isl1 as a potential biomarker for diagnosis and treatment
topic uterine neuroendocrine tumors
single-cell rna sequencing
isl1
cell proliferation and migration
url https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903100
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