BHLHE22 Expression Is Associated with a Proinflammatory Immune Microenvironment and Confers a Favorable Prognosis in Endometrial Cancer
Endometrial cancer (EC) rates are rising annually. Additional prediction markers need to be evaluated because only 10–20% of EC cases show an objective response to immune-checkpoint inhibitors (ICIs). Our previous methylomic study found that BHLHE22 is hypermethylated in EC tissues and can be detect...
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| Published in | International journal of molecular sciences Vol. 23; no. 13; p. 7158 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Basel
MDPI AG
28.06.2022
MDPI |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1422-0067 1661-6596 1422-0067 |
| DOI | 10.3390/ijms23137158 |
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| Abstract | Endometrial cancer (EC) rates are rising annually. Additional prediction markers need to be evaluated because only 10–20% of EC cases show an objective response to immune-checkpoint inhibitors (ICIs). Our previous methylomic study found that BHLHE22 is hypermethylated in EC tissues and can be detected using a Pap-smear sample. BHLHE22, a basic helix loop helix transcription factor family member, is known as a transcriptional repressor and is involved in cell differentiation. However, the role of BHLHE22 in EC remains poorly understood. Herein, we analyzed BHLHE22 expression in 54 paired cancer and normal endometrial tissue samples, and confirmed with databases (TCGA, GTEx, and human protein atlas). We found that BHLHE22 protein expression was significantly downregulated in EC compared with normal endometrium. High BHLHE22 expression was associated with microsatellite-instable subtype, endometrioid type, grade, and age. It showed a significant favorable survival. BHLHE22 overexpression inhibited the proliferation and migration of EC cells. Functional enrichment analysis showed that BHLHE22 was significantly associated with immune-related pathways. Furthermore, BHLHE22 was positively correlated with proinflammatory leukocyte infiltration and expression of chemokine genes in EC. In conclusion, BHLHE22 regulates immune-related pathways and modulates the immune microenvironment of EC. |
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| AbstractList | Endometrial cancer (EC) rates are rising annually. Additional prediction markers need to be evaluated because only 10–20% of EC cases show an objective response to immune-checkpoint inhibitors (ICIs). Our previous methylomic study found that BHLHE22 is hypermethylated in EC tissues and can be detected using a Pap-smear sample. BHLHE22, a basic helix loop helix transcription factor family member, is known as a transcriptional repressor and is involved in cell differentiation. However, the role of BHLHE22 in EC remains poorly understood. Herein, we analyzed BHLHE22 expression in 54 paired cancer and normal endometrial tissue samples, and confirmed with databases (TCGA, GTEx, and human protein atlas). We found that BHLHE22 protein expression was significantly downregulated in EC compared with normal endometrium. High BHLHE22 expression was associated with microsatellite-instable subtype, endometrioid type, grade, and age. It showed a significant favorable survival. BHLHE22 overexpression inhibited the proliferation and migration of EC cells. Functional enrichment analysis showed that BHLHE22 was significantly associated with immune-related pathways. Furthermore, BHLHE22 was positively correlated with proinflammatory leukocyte infiltration and expression of chemokine genes in EC. In conclusion, BHLHE22 regulates immune-related pathways and modulates the immune microenvironment of EC. Endometrial cancer (EC) rates are rising annually. Additional prediction markers need to be evaluated because only 10-20% of EC cases show an objective response to immune-checkpoint inhibitors (ICIs). Our previous methylomic study found that BHLHE22 is hypermethylated in EC tissues and can be detected using a Pap-smear sample. BHLHE22, a basic helix loop helix transcription factor family member, is known as a transcriptional repressor and is involved in cell differentiation. However, the role of BHLHE22 in EC remains poorly understood. Herein, we analyzed BHLHE22 expression in 54 paired cancer and normal endometrial tissue samples, and confirmed with databases (TCGA, GTEx, and human protein atlas). We found that BHLHE22 protein expression was significantly downregulated in EC compared with normal endometrium. High BHLHE22 expression was associated with microsatellite-instable subtype, endometrioid type, grade, and age. It showed a significant favorable survival. BHLHE22 overexpression inhibited the proliferation and migration of EC cells. Functional enrichment analysis showed that BHLHE22 was significantly associated with immune-related pathways. Furthermore, BHLHE22 was positively correlated with proinflammatory leukocyte infiltration and expression of chemokine genes in EC. In conclusion, BHLHE22 regulates immune-related pathways and modulates the immune microenvironment of EC.Endometrial cancer (EC) rates are rising annually. Additional prediction markers need to be evaluated because only 10-20% of EC cases show an objective response to immune-checkpoint inhibitors (ICIs). Our previous methylomic study found that BHLHE22 is hypermethylated in EC tissues and can be detected using a Pap-smear sample. BHLHE22, a basic helix loop helix transcription factor family member, is known as a transcriptional repressor and is involved in cell differentiation. However, the role of BHLHE22 in EC remains poorly understood. Herein, we analyzed BHLHE22 expression in 54 paired cancer and normal endometrial tissue samples, and confirmed with databases (TCGA, GTEx, and human protein atlas). We found that BHLHE22 protein expression was significantly downregulated in EC compared with normal endometrium. High BHLHE22 expression was associated with microsatellite-instable subtype, endometrioid type, grade, and age. It showed a significant favorable survival. BHLHE22 overexpression inhibited the proliferation and migration of EC cells. Functional enrichment analysis showed that BHLHE22 was significantly associated with immune-related pathways. Furthermore, BHLHE22 was positively correlated with proinflammatory leukocyte infiltration and expression of chemokine genes in EC. In conclusion, BHLHE22 regulates immune-related pathways and modulates the immune microenvironment of EC. |
| Author | Chen, Lin-Yu Weng, Yu-Chun Wang, Hui-Chen Su, Po-Hsuan Darmawi Lai, Hung-Cheng Liew, Phui-Ly Huang, Rui-Lan |
| AuthorAffiliation | 5 Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei 235, Taiwan; lilyliew@tmu.edu.tw 1 International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; d142108012@tmu.edu.tw 3 Department of Histology, Faculty of Medicine, Universitas Riau, Pekanbaru 28293, Indonesia 4 Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei 235, Taiwan 6 Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan 8 Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, National Defense Medical Center, Taipei 114, Taiwan 7 Department of Obstetrics and Gynecology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; egg-0420@yahoo.com.tw 2 Translational Epigenetics Center, Shuang Ho Hospital, Taipei Medical University, New Taipei 235, Taiwan; maple916chen@gmail.com (L.-Y.C.); pohsuansu@gmail.com (P.-H. |
| AuthorAffiliation_xml | – name: 7 Department of Obstetrics and Gynecology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; egg-0420@yahoo.com.tw – name: 1 International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; d142108012@tmu.edu.tw – name: 4 Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei 235, Taiwan – name: 6 Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan – name: 5 Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei 235, Taiwan; lilyliew@tmu.edu.tw – name: 2 Translational Epigenetics Center, Shuang Ho Hospital, Taipei Medical University, New Taipei 235, Taiwan; maple916chen@gmail.com (L.-Y.C.); pohsuansu@gmail.com (P.-H.S.); kxther@gmail.com (Y.-C.W.); gyntsgh@gmail.com (R.-L.H.) – name: 8 Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, National Defense Medical Center, Taipei 114, Taiwan – name: 3 Department of Histology, Faculty of Medicine, Universitas Riau, Pekanbaru 28293, Indonesia |
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| SubjectTerms | Cell growth Cytokines DNA methylation Endometrial cancer Endometrium Estrogens Genes Medical prognosis Proteins T cell receptors Transcription factors |
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| Title | BHLHE22 Expression Is Associated with a Proinflammatory Immune Microenvironment and Confers a Favorable Prognosis in Endometrial Cancer |
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