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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IMR Press
2024-03-01
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Series: | Frontiers in Bioscience-Landmark |
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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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language | English |
last_indexed | 2024-04-24T17:38:45Z |
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series | Frontiers in Bioscience-Landmark |
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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