A Comparative Analysis of the Gene Expression Profiles of Small Cell Esophageal Carcinoma, Small Cell Lung Cancer, and Esophageal Adeno/Squamous Carcinoma
Purpose/objectives: Primary small cell esophageal carcinoma (SCEC) is a rare malignancy without an established treatment strategy. This study investigated the gene expression profile of SCEC and compared it with the expression profiles of small cell lung cancer (SCLC) and esophageal adeno/squamous c...
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Frontiers Media S.A.
2021-07-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fsurg.2021.655159/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Di Liu Di Liu Di Liu Junmiao Wen Junmiao Wen Junmiao Wen Jiayan Chen Jiayan Chen Jiayan Chen Boyan Wang Boyan Wang Boyan Wang Xinyan Xu Xinyan Xu Xinyan Xu Zhen Zhang Zhen Zhang Zhen Zhang Min Fan Min Fan Min Fan |
spellingShingle |
Di Liu Di Liu Di Liu Junmiao Wen Junmiao Wen Junmiao Wen Jiayan Chen Jiayan Chen Jiayan Chen Boyan Wang Boyan Wang Boyan Wang Xinyan Xu Xinyan Xu Xinyan Xu Zhen Zhang Zhen Zhang Zhen Zhang Min Fan Min Fan Min Fan A Comparative Analysis of the Gene Expression Profiles of Small Cell Esophageal Carcinoma, Small Cell Lung Cancer, and Esophageal Adeno/Squamous Carcinoma Frontiers in Surgery small cell esophageal carcinoma small cell lung cancer esophageal squamous carcinoma gene expression profile esophageal adenocarcinoma |
author_facet |
Di Liu Di Liu Di Liu Junmiao Wen Junmiao Wen Junmiao Wen Jiayan Chen Jiayan Chen Jiayan Chen Boyan Wang Boyan Wang Boyan Wang Xinyan Xu Xinyan Xu Xinyan Xu Zhen Zhang Zhen Zhang Zhen Zhang Min Fan Min Fan Min Fan |
author_sort |
Di Liu |
title |
A Comparative Analysis of the Gene Expression Profiles of Small Cell Esophageal Carcinoma, Small Cell Lung Cancer, and Esophageal Adeno/Squamous Carcinoma |
title_short |
A Comparative Analysis of the Gene Expression Profiles of Small Cell Esophageal Carcinoma, Small Cell Lung Cancer, and Esophageal Adeno/Squamous Carcinoma |
title_full |
A Comparative Analysis of the Gene Expression Profiles of Small Cell Esophageal Carcinoma, Small Cell Lung Cancer, and Esophageal Adeno/Squamous Carcinoma |
title_fullStr |
A Comparative Analysis of the Gene Expression Profiles of Small Cell Esophageal Carcinoma, Small Cell Lung Cancer, and Esophageal Adeno/Squamous Carcinoma |
title_full_unstemmed |
A Comparative Analysis of the Gene Expression Profiles of Small Cell Esophageal Carcinoma, Small Cell Lung Cancer, and Esophageal Adeno/Squamous Carcinoma |
title_sort |
comparative analysis of the gene expression profiles of small cell esophageal carcinoma, small cell lung cancer, and esophageal adeno/squamous carcinoma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Surgery |
issn |
2296-875X |
publishDate |
2021-07-01 |
description |
Purpose/objectives: Primary small cell esophageal carcinoma (SCEC) is a rare malignancy without an established treatment strategy. This study investigated the gene expression profile of SCEC and compared it with the expression profiles of small cell lung cancer (SCLC) and esophageal adeno/squamous carcinoma (EAC/ESCC).Materials/methods: All patients with SCEC, SCLC, and EAC/ESCC in the Surveillance, Epidemiology, and End Results (SEER) database 1973–2014 were included. Overall survival (OS) and prognostic analysis were conducted. De novo expression array analysis was performed on three pairs of frozen primary SCEC tissues and the corresponding normal samples from the institutional tissue bank using the Affymetrix HG U133 plus 2.0 Array. These data were complemented with public domain expression data sets from the Gene Expression Omnibus (GEO) repository using the same working platforms, which included primary SCLC, EAC/ESCC, and normal lung/esophagus specimens (series GSE30219 and GSE26886). After individual normalization, the primary tumors were submitted to statistical analysis (GeneSpring GX 13.0) to identify the differentially expressed genes (DEGs) relative to their paired normal tissues. Enrichments of genes categorized by function and gene interactions were analyzed by DAVID 6.8 and STRING 11.0, respectively.Results: The clinical outcomes of the patients with SCEC were significantly more worse than those with EAC/ESCC and SCLC in the SEER database. SCEC had more DEGs in common with SCLC than EAC/ESCC [829 vs. 450; false discovery rate (FDR) < 0.01; and fold change ≥2], leading to a stronger correlation between SCEC and SCLC (Pearson's correlation coefficient was 0.60 for SCEC vs. SCLC, 0.51 or 0.45 for SCEC vs. ESCC or EAC, and the coefficient was 0.73 for ESCC vs. EAC). Similar findings were obtained by principal component analysis (PCA) using all DEGs retrieved from these four groups. Functional annotation showed that a higher proportion of pathways and biological processes were common between SCEC and SCLC and were associated with the cell cycle (mitosis), DNA replication, telomere maintenance, DNA repair, and P53 and RB pathways (Benjamini p < 0.05). Compared with EAC/ESCC, SCEC shared more co-upregulated DEGs coding for the aforementioned common pathways with SCLC (584 vs. 155). In addition, SCEC and SCLC were found to have possessed overlapping gene-interactive networks, with centromere protein F (CENPF), never in mitosis gene A-related kinase 2 (NEK2), kinesin family member 11 (KIF11), thymopoietin (TMPO), and forkhead box protein M1 (FOXM1) as common skeletons centered by gene regulatory network (NUF2).Conclusions: This study is the first attempt to examine the genomic signatures of SCEC at the transcriptomic level and compare the expression profiles between SCEC, SCLC, and EAC/ESCC. Our preliminary data indicate that SCEC and SCLC display notably similar patterns of gene expression for mitosis and DNA repair. Further validation studies are warranted. |
topic |
small cell esophageal carcinoma small cell lung cancer esophageal squamous carcinoma gene expression profile esophageal adenocarcinoma |
url |
https://www.frontiersin.org/articles/10.3389/fsurg.2021.655159/full |
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doaj-c5c38ca94d75453382ff6d205ea3d6f92021-07-30T04:59:18ZengFrontiers Media S.A.Frontiers in Surgery2296-875X2021-07-01810.3389/fsurg.2021.655159655159A Comparative Analysis of the Gene Expression Profiles of Small Cell Esophageal Carcinoma, Small Cell Lung Cancer, and Esophageal Adeno/Squamous CarcinomaDi Liu0Di Liu1Di Liu2Junmiao Wen3Junmiao Wen4Junmiao Wen5Jiayan Chen6Jiayan Chen7Jiayan Chen8Boyan Wang9Boyan Wang10Boyan Wang11Xinyan Xu12Xinyan Xu13Xinyan Xu14Zhen Zhang15Zhen Zhang16Zhen Zhang17Min Fan18Min Fan19Min Fan20Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Radiation Oncology, Shanghai, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Radiation Oncology, Shanghai, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Radiation Oncology, Shanghai, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Radiation Oncology, Shanghai, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Radiation Oncology, Shanghai, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Radiation Oncology, Shanghai, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Radiation Oncology, Shanghai, ChinaPurpose/objectives: Primary small cell esophageal carcinoma (SCEC) is a rare malignancy without an established treatment strategy. This study investigated the gene expression profile of SCEC and compared it with the expression profiles of small cell lung cancer (SCLC) and esophageal adeno/squamous carcinoma (EAC/ESCC).Materials/methods: All patients with SCEC, SCLC, and EAC/ESCC in the Surveillance, Epidemiology, and End Results (SEER) database 1973–2014 were included. Overall survival (OS) and prognostic analysis were conducted. De novo expression array analysis was performed on three pairs of frozen primary SCEC tissues and the corresponding normal samples from the institutional tissue bank using the Affymetrix HG U133 plus 2.0 Array. These data were complemented with public domain expression data sets from the Gene Expression Omnibus (GEO) repository using the same working platforms, which included primary SCLC, EAC/ESCC, and normal lung/esophagus specimens (series GSE30219 and GSE26886). After individual normalization, the primary tumors were submitted to statistical analysis (GeneSpring GX 13.0) to identify the differentially expressed genes (DEGs) relative to their paired normal tissues. Enrichments of genes categorized by function and gene interactions were analyzed by DAVID 6.8 and STRING 11.0, respectively.Results: The clinical outcomes of the patients with SCEC were significantly more worse than those with EAC/ESCC and SCLC in the SEER database. SCEC had more DEGs in common with SCLC than EAC/ESCC [829 vs. 450; false discovery rate (FDR) < 0.01; and fold change ≥2], leading to a stronger correlation between SCEC and SCLC (Pearson's correlation coefficient was 0.60 for SCEC vs. SCLC, 0.51 or 0.45 for SCEC vs. ESCC or EAC, and the coefficient was 0.73 for ESCC vs. EAC). Similar findings were obtained by principal component analysis (PCA) using all DEGs retrieved from these four groups. Functional annotation showed that a higher proportion of pathways and biological processes were common between SCEC and SCLC and were associated with the cell cycle (mitosis), DNA replication, telomere maintenance, DNA repair, and P53 and RB pathways (Benjamini p < 0.05). Compared with EAC/ESCC, SCEC shared more co-upregulated DEGs coding for the aforementioned common pathways with SCLC (584 vs. 155). In addition, SCEC and SCLC were found to have possessed overlapping gene-interactive networks, with centromere protein F (CENPF), never in mitosis gene A-related kinase 2 (NEK2), kinesin family member 11 (KIF11), thymopoietin (TMPO), and forkhead box protein M1 (FOXM1) as common skeletons centered by gene regulatory network (NUF2).Conclusions: This study is the first attempt to examine the genomic signatures of SCEC at the transcriptomic level and compare the expression profiles between SCEC, SCLC, and EAC/ESCC. Our preliminary data indicate that SCEC and SCLC display notably similar patterns of gene expression for mitosis and DNA repair. Further validation studies are warranted.https://www.frontiersin.org/articles/10.3389/fsurg.2021.655159/fullsmall cell esophageal carcinomasmall cell lung canceresophageal squamous carcinomagene expression profileesophageal adenocarcinoma |