A Novel Notch-Related Gene Signature for Prognosis and Immune Response Prediction in Ovarian Cancer
<i>Background and Objectives:</i> Notch is a fascinating signaling pathway. It is extensively involved in tumor growth, cancer stem cells, metastasis, and treatment resistance and plays important roles in metabolic regulation, tumor microenvironment, and tumor immunity. However, the role...
| Main Authors: | , , , , |
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/7/1277 |
| _version_ | 1797588363132272640 |
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| author | Yanan Pi Fusheng Sun Zhaocong Zhang Xiaoli Liu Ge Lou |
| author_facet | Yanan Pi Fusheng Sun Zhaocong Zhang Xiaoli Liu Ge Lou |
| author_sort | Yanan Pi |
| collection | DOAJ |
| description | <i>Background and Objectives:</i> Notch is a fascinating signaling pathway. It is extensively involved in tumor growth, cancer stem cells, metastasis, and treatment resistance and plays important roles in metabolic regulation, tumor microenvironment, and tumor immunity. However, the role of Notch in ovarian cancer (OC) has yet to be fully understood. Therefore, this study systematically described the expression, mutation, and copy number variation of genes in the Notch signaling pathway in OC and evaluated the relationship between gene mutation and Overall Survival (OS) prognosis. <i>Materials and Methods:</i> Notch risk score (NTRS) was established by univariate Cox regression analysis combined with Lasso regression analysis, and the efficacy of NTRS in predicting prognosis and immunotherapy response in patients with OC was verified. We further assessed the correlations of NTRS with clinical features, immune infiltration level, immune checkpoint expression, and immune characteristics. Additionally, differential expression and functions of the fourteen signature genes were confirmed via vitro assays. <i>Results:</i> The results showed that Notch genes (NTGs) were markedly differentiated between tumor and normal tissues, which may help to explain the high heterogeneity in the biological characteristics and therapeutic outcomes of human OC. A Notch risk (NTR) prognostic model based on 11 key NTGs was successfully constructed. Tumors with high Notch risk scores (NTRS) were independently associated with shorter overall survival and poorer immunotherapy outcomes. We further assessed the correlations of NTRS with immune characteristics. The results showed that NTGs play a key role in regulating the tumor immune microenvironment. Additionally, we validated the baseline and induced expressions of 14 prognosis-related NTGs in our own OC samples. In vitro assays confirmed that the knockdown of NCOR2 and APH1B and overexpression of HEY2 and SKP2 could inhibit the proliferation, invasion, and migration of OC cells. <i>Conclusions:</i> These findings emphasize that Notch multilayer changes are associated with the prognosis of patients with OC and the characteristics of immune cell infiltration. Our predictive signature may predict the prognosis and immunotherapy response of OC patients in an independent manner. NCOR2, APH1B, HEY2, and SKP2 may more prominently represent important indicators to improve patient prognosis. |
| first_indexed | 2024-03-11T00:50:55Z |
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| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-11T00:50:55Z |
| publishDate | 2023-07-01 |
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| series | Medicina |
| spelling | doaj.art-7991f6e8e8b5406383dca9bddcf185cf2023-11-18T20:24:25ZengMDPI AGMedicina1010-660X1648-91442023-07-01597127710.3390/medicina59071277A Novel Notch-Related Gene Signature for Prognosis and Immune Response Prediction in Ovarian CancerYanan Pi0Fusheng Sun1Zhaocong Zhang2Xiaoli Liu3Ge Lou4Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin 150086, ChinaDepartment of Gynecology, Harbin Medical University Cancer Hospital, Harbin 150086, ChinaDepartment of Gynecology, Harbin Medical University Cancer Hospital, Harbin 150086, ChinaHarbin Obstetrics and Gynecology Hospital, Harbin Medical University, Harbin 150086, ChinaDepartment of Gynecology, Harbin Medical University Cancer Hospital, Harbin 150086, China<i>Background and Objectives:</i> Notch is a fascinating signaling pathway. It is extensively involved in tumor growth, cancer stem cells, metastasis, and treatment resistance and plays important roles in metabolic regulation, tumor microenvironment, and tumor immunity. However, the role of Notch in ovarian cancer (OC) has yet to be fully understood. Therefore, this study systematically described the expression, mutation, and copy number variation of genes in the Notch signaling pathway in OC and evaluated the relationship between gene mutation and Overall Survival (OS) prognosis. <i>Materials and Methods:</i> Notch risk score (NTRS) was established by univariate Cox regression analysis combined with Lasso regression analysis, and the efficacy of NTRS in predicting prognosis and immunotherapy response in patients with OC was verified. We further assessed the correlations of NTRS with clinical features, immune infiltration level, immune checkpoint expression, and immune characteristics. Additionally, differential expression and functions of the fourteen signature genes were confirmed via vitro assays. <i>Results:</i> The results showed that Notch genes (NTGs) were markedly differentiated between tumor and normal tissues, which may help to explain the high heterogeneity in the biological characteristics and therapeutic outcomes of human OC. A Notch risk (NTR) prognostic model based on 11 key NTGs was successfully constructed. Tumors with high Notch risk scores (NTRS) were independently associated with shorter overall survival and poorer immunotherapy outcomes. We further assessed the correlations of NTRS with immune characteristics. The results showed that NTGs play a key role in regulating the tumor immune microenvironment. Additionally, we validated the baseline and induced expressions of 14 prognosis-related NTGs in our own OC samples. In vitro assays confirmed that the knockdown of NCOR2 and APH1B and overexpression of HEY2 and SKP2 could inhibit the proliferation, invasion, and migration of OC cells. <i>Conclusions:</i> These findings emphasize that Notch multilayer changes are associated with the prognosis of patients with OC and the characteristics of immune cell infiltration. Our predictive signature may predict the prognosis and immunotherapy response of OC patients in an independent manner. NCOR2, APH1B, HEY2, and SKP2 may more prominently represent important indicators to improve patient prognosis.https://www.mdpi.com/1648-9144/59/7/1277ovarian cancerNotchNTRSsurvival analysisimmunotherapy |
| spellingShingle | Yanan Pi Fusheng Sun Zhaocong Zhang Xiaoli Liu Ge Lou A Novel Notch-Related Gene Signature for Prognosis and Immune Response Prediction in Ovarian Cancer Medicina ovarian cancer Notch NTRS survival analysis immunotherapy |
| title | A Novel Notch-Related Gene Signature for Prognosis and Immune Response Prediction in Ovarian Cancer |
| title_full | A Novel Notch-Related Gene Signature for Prognosis and Immune Response Prediction in Ovarian Cancer |
| title_fullStr | A Novel Notch-Related Gene Signature for Prognosis and Immune Response Prediction in Ovarian Cancer |
| title_full_unstemmed | A Novel Notch-Related Gene Signature for Prognosis and Immune Response Prediction in Ovarian Cancer |
| title_short | A Novel Notch-Related Gene Signature for Prognosis and Immune Response Prediction in Ovarian Cancer |
| title_sort | novel notch related gene signature for prognosis and immune response prediction in ovarian cancer |
| topic | ovarian cancer Notch NTRS survival analysis immunotherapy |
| url | https://www.mdpi.com/1648-9144/59/7/1277 |
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