AIM2 Inflammasome in Tumor Cells as a Biomarker for Predicting the Treatment Response to Antiangiogenic Therapy in Epithelial Ovarian Cancer Patients
Antiangiogenic therapy, such as bevacizumab (BEV), has improved progression-free survival (PFS) and overall survival (OS) in high-risk patients with epithelial ovarian cancer (EOC) according to several clinical trials. Clinically, no reliable molecular biomarker is available to predict the treatment...
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MDPI AG
2021-09-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/19/4529 |
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| author | Po-Chao Hsu Tai-Kuang Chao Yu-Ching Chou Mu-Hsien Yu Yu-Chi Wang Yi-Hsin Lin Yi-Liang Lee Li-Chun Liu Cheng-Chang Chang |
| author_facet | Po-Chao Hsu Tai-Kuang Chao Yu-Ching Chou Mu-Hsien Yu Yu-Chi Wang Yi-Hsin Lin Yi-Liang Lee Li-Chun Liu Cheng-Chang Chang |
| author_sort | Po-Chao Hsu |
| collection | DOAJ |
| description | Antiangiogenic therapy, such as bevacizumab (BEV), has improved progression-free survival (PFS) and overall survival (OS) in high-risk patients with epithelial ovarian cancer (EOC) according to several clinical trials. Clinically, no reliable molecular biomarker is available to predict the treatment response to antiangiogenic therapy. Immune-related proteins can indirectly contribute to angiogenesis by regulating stromal cells in the tumor microenvironment. This study was performed to search biomarkers for prediction of the BEV treatment response in EOC patients. We conducted a hospital-based retrospective study from March 2013 to May 2020. Tissues from 78 Taiwanese patients who were newly diagnosed with EOC and peritoneal serous papillary carcinoma (PSPC) and received BEV therapy were collected. We used immunohistochemistry (IHC) staining and analyzed the expression of these putative biomarkers (complement component 3 (C3), complement component 5 (C5), and absent in melanoma 2 (AIM2)) based on the staining area and intensity of the color reaction to predict BEV efficacy in EOC patients. The immunostaining scores of AIM2 were significantly higher in the BEV-resistant group (RG) than in the BEV-sensitive group (SG) (355.5 vs. 297.1, <i>p</i> < 0.001). A high level of AIM2 (mean value > 310) conferred worse PFS after treatment with BEV than a low level of AIM2 (13.58 vs. 19.36 months, adjusted hazard ratio (HR) = 4.44, 95% confidence interval (CI) = 2.01–9.80, <i>p</i> < 0.001). There were no significant differences in C3 (<i>p</i> = 0.077) or C5 (<i>p</i> = 0.326) regarding BEV efficacy. AIM2 inflammasome expression can be a histopathological biomarker to predict the antiangiogenic therapy benefit in EOC patients. The molecular mechanism requires further investigation. |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T06:57:44Z |
| publishDate | 2021-09-01 |
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| spelling | doaj.art-33d58110a5504f3791e8394ba1d9ec482023-11-22T16:20:49ZengMDPI AGJournal of Clinical Medicine2077-03832021-09-011019452910.3390/jcm10194529AIM2 Inflammasome in Tumor Cells as a Biomarker for Predicting the Treatment Response to Antiangiogenic Therapy in Epithelial Ovarian Cancer PatientsPo-Chao Hsu0Tai-Kuang Chao1Yu-Ching Chou2Mu-Hsien Yu3Yu-Chi Wang4Yi-Hsin Lin5Yi-Liang Lee6Li-Chun Liu7Cheng-Chang Chang8Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanSchool of Public Health, National Defense Medical Center, Taipei 114, TaiwanDepartment of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanAntiangiogenic therapy, such as bevacizumab (BEV), has improved progression-free survival (PFS) and overall survival (OS) in high-risk patients with epithelial ovarian cancer (EOC) according to several clinical trials. Clinically, no reliable molecular biomarker is available to predict the treatment response to antiangiogenic therapy. Immune-related proteins can indirectly contribute to angiogenesis by regulating stromal cells in the tumor microenvironment. This study was performed to search biomarkers for prediction of the BEV treatment response in EOC patients. We conducted a hospital-based retrospective study from March 2013 to May 2020. Tissues from 78 Taiwanese patients who were newly diagnosed with EOC and peritoneal serous papillary carcinoma (PSPC) and received BEV therapy were collected. We used immunohistochemistry (IHC) staining and analyzed the expression of these putative biomarkers (complement component 3 (C3), complement component 5 (C5), and absent in melanoma 2 (AIM2)) based on the staining area and intensity of the color reaction to predict BEV efficacy in EOC patients. The immunostaining scores of AIM2 were significantly higher in the BEV-resistant group (RG) than in the BEV-sensitive group (SG) (355.5 vs. 297.1, <i>p</i> < 0.001). A high level of AIM2 (mean value > 310) conferred worse PFS after treatment with BEV than a low level of AIM2 (13.58 vs. 19.36 months, adjusted hazard ratio (HR) = 4.44, 95% confidence interval (CI) = 2.01–9.80, <i>p</i> < 0.001). There were no significant differences in C3 (<i>p</i> = 0.077) or C5 (<i>p</i> = 0.326) regarding BEV efficacy. AIM2 inflammasome expression can be a histopathological biomarker to predict the antiangiogenic therapy benefit in EOC patients. The molecular mechanism requires further investigation.https://www.mdpi.com/2077-0383/10/19/4529epithelial ovarian cancer (EOC)antiangiogenic therapybevacizumabcomplement C3C5AIM2 inflammasome |
| spellingShingle | Po-Chao Hsu Tai-Kuang Chao Yu-Ching Chou Mu-Hsien Yu Yu-Chi Wang Yi-Hsin Lin Yi-Liang Lee Li-Chun Liu Cheng-Chang Chang AIM2 Inflammasome in Tumor Cells as a Biomarker for Predicting the Treatment Response to Antiangiogenic Therapy in Epithelial Ovarian Cancer Patients Journal of Clinical Medicine epithelial ovarian cancer (EOC) antiangiogenic therapy bevacizumab complement C3 C5 AIM2 inflammasome |
| title | AIM2 Inflammasome in Tumor Cells as a Biomarker for Predicting the Treatment Response to Antiangiogenic Therapy in Epithelial Ovarian Cancer Patients |
| title_full | AIM2 Inflammasome in Tumor Cells as a Biomarker for Predicting the Treatment Response to Antiangiogenic Therapy in Epithelial Ovarian Cancer Patients |
| title_fullStr | AIM2 Inflammasome in Tumor Cells as a Biomarker for Predicting the Treatment Response to Antiangiogenic Therapy in Epithelial Ovarian Cancer Patients |
| title_full_unstemmed | AIM2 Inflammasome in Tumor Cells as a Biomarker for Predicting the Treatment Response to Antiangiogenic Therapy in Epithelial Ovarian Cancer Patients |
| title_short | AIM2 Inflammasome in Tumor Cells as a Biomarker for Predicting the Treatment Response to Antiangiogenic Therapy in Epithelial Ovarian Cancer Patients |
| title_sort | aim2 inflammasome in tumor cells as a biomarker for predicting the treatment response to antiangiogenic therapy in epithelial ovarian cancer patients |
| topic | epithelial ovarian cancer (EOC) antiangiogenic therapy bevacizumab complement C3 C5 AIM2 inflammasome |
| url | https://www.mdpi.com/2077-0383/10/19/4529 |
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