AIM2 Inflammasome in Tumor Cells as a Biomarker for Predicting the Treatment Response to Antiangiogenic Therapy in Epithelial Ovarian Cancer Patients
Open accessAbstract
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, p < 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, p < 0.001). There were no significant differences in C3 (p = 0.077) or C5 (p = 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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Unlike for PARP inhibitors, there are no clinically approved biomarkers to predict responses of women with ovarian cancer to the anti-angiogenic bevacizumab.
“Unlike for PARPis, there are no clinically approved biomarkers to predict responses of women with ovarian cancer to the anti-angiogenic bevacizumab, although numerous studies have focused on this area (Buechel et al., 2021; Gao et al., 2021; Hsu et al., 2021).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Hsu et al., 2021
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- Authors
- Hsu, P.-C., Chao, T.-K., Chou, Y.-C., Yu, M.-H., Wang, Y.-C., Lin, Y.-H., Lee, Y.-L., Liu, L.-C., & Chang, C.-C.
- Affiliations
- Tri-Service General Hospital (TW)
- National Defense Medical Center (TW)
- Corresponding author
- Chang, Cheng-Chang
- ORCID
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2021-09-30
- Volume
- 10
- Issue
- 19
- Pages
- 4529
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC8509490
- OpenAlex
- W3202417786
- Cited by
- 20
- References
- 33
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 6
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Veterans General Hospital, Tri-Service General Hospital and Academia Sinica Joint Research Program (VTA110-T-4-1)
- Tri-Service General Hospital (TSGH-D-110136)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Keywords
- AIM2 inflammasome, epithelial ovarian cancer, bevacizumab, anti-angiogenic therapy, treatment response prediction, prognostic factors, complement C3, complement component 5, tumor microenvironment, progression-free survival
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