Table 1. Synopsis of Involved Studies.
ACEIs: angiotensin-converting enzyme inhibitors, ARBs: angiotensin receptor blockers, ANOVA: analysis of variance, MTT: 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide, CAM: chorioallantoic membrane, RT-PCR: real-time polymerase chain reaction
| Reference | Study characteristics | Patients/tissue samples/cell lines | Tests performed | Statistical analysis |
| Natarajan et al. 2019 [4] | Histopathological study; Animal study | High grade serous ovarian cancer cell line: OVCAR5, OVCAR8 Human peritoneal mesothelial cell line: LP-9 Primary human mesothelial cells (PHMC): omentum of patients with benign disease Mouse ovarian cancer cell line: ID8 | Gene signature analysis, siRNA analysis, collagen gels, and confocal microscopy, invasion assay, real-time quantitative polymerase chain reaction (qPCR), Western blotting, Immunohistochemistry, immunofluorescence, second harmonic generation microscopy, picrosirius red staining | It was done with two-way ANOVA and a two-tailed unpaired t-test. Statistical significance of p-value <0.05. |
| Yeung et al. 2019 [10] | Histopathological study; Animal study | OVCAR432 cells | IVIS bioluminescence fluorescence imaging system | It was done with a two-tailed unpaired Student’s t-test—the statistical significance of p-value <0.05. |
| Zhao et al. 2019 [6] | Retrospective analysis; Animal study | One hundred and twenty-three patients with stage IIIC or IV who were previously taking ACEIs or ARBs compared to 99 patients taking other anti-hypertensives SKOV3ip1, HeyA8 | Gaussia Luciferase measurement, extravasation of doxorubicin by histology, planar-cut method to measure solid stress, unconfined compression test to quantify Young's modulus (stiffness), lymphatic vessel drainage function study, histology and immunohistochemistry, mRNA, miRNA extraction and array analysis, transient transfections and reporter gene assays | It was done using logistic regression. It was done with the Student’s t-test (two-tailed) or Mann-Whitney U test (two-tailed), two-sided Fisher's exact test. |
| Grither et al. 2018 [13] | Histopathological study | Patient-derived tumor cells–ascites from patients with ovarian cancer (POV) 1,9,10,12 Established human ovarian tumor cell lines—A2780, SKOV3ip1, OVCAR3, OVCAR5 | Western blot analysis, gelatin zymography, immunohistochemical analysis using human tissue microarrays, Invasion and migration assays, proliferation assay, real-time polymerase chain reaction (PCR) with reverse transcription, fibronectin cleavage assay, cell spreading assay, spheroid-induced mesothelial clearance assay, survival analysis. | It was done using a two-tailed unpaired Student’s t-test with a statistical significance of p-value <0.05. |
| Guo et al. 2017 [12] | Histopathological study; Animal study | Tissue samples from 72 patients of primary epithelial ovarian cancer (PEOC)- 34 out of 72 were stage I-II, and the remaining 38 patients were stage III-IV. Ten normal tissue samples. Human ovarian adenocarcinoma-ascites of a 64-year-old woman: SKOV3 Human ovarian clear cell carcinoma: ES2 Ovarian adenocarcinoma: A2780 Ovarian serous adenocarcinoma-ascites of Chinese patients: HO8910 Immortalized ovarian surface superficial epithelium cell line: IOSE | Transwell migration and invasion assays, wound healing assays, cell adhesion assays, phospho-antibody microarray, Western blotting, Co-immunoprecipitation, RNA extraction, and real-time RT-PCR assays, immunohistochemistry | It was done with a double-sided Student’s t-test and Chi-square test. Statistical significance of p-value <0.05. |
| Fogg et al. 2019 [7] | Histopathological study | High grade serous ovarian cancer (HGSOC) cell lines: OVCAR3, OV90, OVCA433 | Polymerase chain reaction (PCR), histological analysis, confocal imaging, and image analysis | Done using one-way ANOVA, two-way ANOVA, or t-test |
| Chan et al. 2016 [25] | Histopathological study | HEYA8, OVCAR8 | Scratch wound invasion assay, scanning electron microscopy imaging, mRNA/miR isolation, and quantitative polymerase chain reaction, predicted miR targeting, Parallel microfiltration, Microfluidic device fabrication, and operation using standard soft lithography, Flow cytometry. | It was done separately for each assay with a Statistical significance of p-value <0.05. |
| Samardzija et al. 2016 [9] | Histopathological study; Animal study | Primary high-grade serous epithelial ovarian tumor and normal ovarian tissues from patients. Four established human epithelial ovarian cancer cell lines: SKOV3, OVCAR5, OVCA433, HEY | Immunofluorescence analysis, RNA extraction and real-time PCR, Western blotting, sphere forming assay, flow cytometric analysis, adhesion assay, gelatin zymography | It was done using two-way ANOVA and Dunnett's multiple comparison test with a Statistical significance of p-value <0.05. |
| Choi et al. 2016 [31] | Histopathological study | Primary human ovarian surface epithelial cell line: MCAS, OVCA432, OVCA433 HPVE6E7 immortalized OSE cell lines. Normal human ovarian surface epithelial (OSE) cell line: OSE7, OSE9 | Immunofluorescence microscopy, immunohistochemical staining of tissue samples, gene expression profiling and network analysis, quantitative real-time reverse transcription PCR, Western blot analysis | It was done with ANOVA and a two-tailed t-test. Statistical significance of p-value <0.05. |
| Liu et al. 2019 [21] | Histopathological study | One hundred and forty paraffin-embedded tissue samples from patients after surgery. Out of 140, 60 were primary epithelial ovarian cancer, 30 were borderline ovarian tumors, 30 benign ovarian tumors, 20 normal ovarian tissues. Cell line- RMG-I-hFUT | Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, Western blot analysis, co-immunoprecipitation assay, Confocal laser scanning microscopy, Cell adhesion assay, immunohistochemical staining, immunocytochemical staining | It was done with Student’s t-test, chi-square test, one-way analysis of variance with LSD or Bonferroni posthoc test, and Kaplan-Meier curves. Statistical significance of p-value <0.05. |
| Klymenko et al. 2017 [30] | Histopathological study | Epithelial ovarian carcinoma cell line: OvCa432, OvCa433, OvCa429, DOV13 Ovarian adenocarcinoma cell line: OVCAR3, SKOV3 Human mesothelial cell line: LP9 | Quantitative polymerase chain reaction of cDNA arrays, Western blot analysis, dual-label immunofluorescence microscopy (DLIF), MCA and tissue scanning electron microscopy (SEM), transmission electron microscopy (TEM), cell proliferation assay, cell migration assay, Matrigel invasion assay, cell-to-collagen adhesion assay, cell-to-mesothelium adhesion assay, cell-to-peritoneum adhesion assay. | Done using Student's t-test |
| Klymenko et al. 2017 [22] | Histopathological study; Animal study | Epithelial ovarian cancer cell lines: OvCa433, DOV13 Human peritoneal mesothelial cell line: LP9 Murine epithelial ovarian cancer cell line: ID8 | Cell adhesion assay, mesothelial clearance assay, scanning electron microscopy (SEM) | It was done using the two-sided Mann-Whitney U test with a Statistical significance of p-value <0.05. |
| Deng et al. 2017 [34] | Histopathological study | Human ovarian cancer cell line: SKOV3, HO-8910 Immortalized ovarian epithelial cell line: IOSE386 | Immunohistochemistry, RNA extraction, and quantitative PCR, DNA methylation analysis, chromatin immunoprecipitation assay, wound healing assay, invasion assay, colony formation in soft agar, cell cytotoxicity assay, flow cytometric detection of apoptosis | It was done using a two-tailed Student’s t-test and Pearson's correlation test with a Statistical significance of p-value <0.05. |
| Ye et al. 2016 [26] | Histopathological study | Eighty-three tissue samples of human ovarian cancer with 18 normal ovarian tissue samples as controls Human ovarian cancer cell lines: SKOV3, ES2, CAOV3, HEY, COV318 | Immunohistochemical staining, RNA interference-based gene silencing experiment, Western blot analysis, quantitative real-time PCR, cell viability assay, in-vitro migration, and invasion assay | Done using Pearson's test, Kaplan-Meier method, Student’s t-test with a statistical significance of p-value <0.05. |
| Shen et al. 2016 [17] | Histopathological study | Tissue samples of 102 patients with epithelial ovarian cancer Epithelial ovarian cancer cell lines: OVCAR3, SKOV3 | Immunohistochemistry, immunofluorescence assay, immunoprecipitation assay, Western blot analysis, cell migration assay, quantitative qPCR | It was done using an unpaired Student’s t-test with a statistical significance of p-value <0.05. |
| Yin et al. 2016 [18] | Histopathological study | Human ovarian cancer cell line: SKOV-3, HO-8910 | Real-time PCR, Western blot, enzyme-linked immunosorbent assay (ELISA), RNA interference, cell adhesion assay, cell viability assay | It was done using ANOVA with a statistical significance of p-value <0.05. |
| Klymenko et al. 2018 [29] | Histopathological study | Epithelial ovarian cancer (EOC) cell lines: OvCa429, OvCa433, DOV13, SKOV3 | Analysis of proliferation, Western blot analysis, RNA extraction, and qPCR, scanning electron microscopy (SEM) | It was done using the two-sided Mann-Whitney U test with a statistical significance of p-value <0.05. |
| Bruney et al. 2016 [16] | Histopathological study | Ovarian cancer cell lines: DOV13, OVCA433, SKOV3, ES2 Human peritoneal mesothelial cell line: LP9 | Western blotting and immunoprecipitation, quantitative real-time PCR (qPCR), Immunohistochemistry, immunofluorescence, adhesion, and invasion assay | Done using Student’s t-test, Mann-Whitney U test, Kruskal-Wallis test with a Statistical significance of p-value <0.05. |
| Price et al. 2020 [27] | Histopathological study; Animal study | Human ovarian cancer cell lines: OVCAR3, OVSAHO, OVCA429, A2780, SKOV3-IP1 Mouse cell line: ID8 IP2 | Immunoblotting, RT-PCR, ID8 IP2 in vivo modeling Histology, flow cytometry, adhesion to ECM, migration scratch/wound assay, invasion assay, proliferation assay, | Done using two-tailed Welsh's t-test, Mental-Cox and Gehan-Breslow- Wilcoxon test with a statistical significance of p-value <0.05. |
| Bruney et al. 2014 [20] | Histopathological study | Ovarian cancer cell line: OVCA433 Ovarian adenocarcinoma cell line: OVCAR3 Human mesothelial cell line: LP9 | Immunohistochemistry, immunofluorescence, quantitative real-time PCR (qPCR), florescence-activated cell sorting (FACS) analysis, enzyme-linked immunosorbent assay, mesothelial cell adhesion assay, meso-mimetic invasion assay, adhesion to peritoneal explant | Done using Student’s t-test |
| Li et al. 2020 [23] | Histopathological study | Human ovarian cancer epithelial cell line: OVCAR3 Human normal ovarian epithelial cell line: IOSE80 | Quantitative reverse transcription PCR (qRT-PCR), cell proliferation activity assay, flow cytometry, transwell cell migration and invasion assay, double luciferase activity assay, Western blot | It was done using a t-test and analysis of variance (ANOVA) with a statistical significance of p-value <0.05. |
| Cheon et al. 2014 [15] | Histopathological study; Animal study | Snap-frozen and paraffin-embedded patient samples. Cancer cell lines: OVCAR3, A2780 Normal cell lines: TRS3 | Microarray data analyses, validation of the 10-gene signature, RNA isolation and RT- qPCR analysis, molecular pathway analysis, in situ hybridization, immunohistochemistry | It was done using an unpaired t-test with a statistical significance of p-value <0.05. |
| Flate and Stalvey 2014 [28] | Histopathological study | Cisplatin sensitive cell line: OV2008 Cisplatin resistant cell line: C13 | Wound healing assay, migration assay, Western blot analysis, microarray | It was done using one-way ANOVA, Tukey, and LSD post hoc tests with a statistical significance of p-value <0.05. |
| Dai et al. 2015 [8] | Histopathological study | Human ovarian cancer cell line: OVCAR-3 | RT-PCR analysis, analysis of cell proliferation using MTT assay, cell migration assessment, cell invasion assay, Western blot | It was done using an independent sample t-test and Post-hoc Turkey-test with a statistical significance of p-value <0.05. |
| Sun et al. 2015 [19] | Histopathological study | Highly metastatic human ovarian cancer cell line: HO-8910PM | Three-dimensional type I collagen invasion and degradation assay, RT-PCR analysis, Western blotting analysis, cell surface biotinylation, fluorescent immunocytochemistry, CAM invasion assay. | N/A |
| Vallen et al. 2014 [33] | Histopathological study | Tissue samples from 25 patients of serous subtype of ovarian cancer Human ovarian cancer cell line: SKOV3 | Immunohistochemistry, reverse phase-high performance liquid chromatography (RP-HPLC) disaccharide analysis, two-dimensional scratch assay, hanging drop experiment, cell migration assay | N/A |
| Pettee et al. 2014 [32] | Histopathological study | Human ovarian cancer cell lines: ES-2, SKOV3, OVCAR3, OVCAR4, OVCA420, OVCA429, OVCA194 | Adhesion, migration and invasion assays, microscopy, Dunn chemotactic migration assay, spheroid formation, and collagen embedding, two-dimensional immunofluorescence (IF), three-dimensional Immunofluorescence and Invasion assay, RhoA GTPase G-LISA activation assay, | It was done using a one-tailed Student’s t-test with a statistical significance of p-value <0.05. |
| Gurler et al. 2015 [11] | Histopathological study | Normal and pathologic ovarian tissue samples: OV2161, OV2087, OV808 Human ovarian cancer cell lines: OVCAR-4, SKOV-3, OAW28, Kuramochi, OVSAHO, OVKATE | Immunohistochemistry, immunofluorescence staining, subcellular fractionation, Western blot, transient transfections, paclitaxel treatment, cell survival, and clonogenic assay | It was done with the Student’s t-test and the statistical significance of p-value <0.05. |
| Triulzi et al. 2014 [35] | Histopathological study; Animal study | Human ovarian cancer cell line: SKOV3 | Proliferation and doxorubicin response assays, Western blotting, confocal microscopy, Immunohistochemical (IHC) analyses, RNA extraction, and quantitative real‐time PCR | It was done using a t-test, chi-square test, two‐tailed unpaired student's t‐test with a statistical significance of p-value <0.05. |
| Wahab et al. 2020 [24] | Histopathological study | Twenty-four unmatched snap-frozen ovarian tissue samples from patients consisting of 11 serous ovarian cancer and 13 normal ovarian tissues Ovarian adenocarcinoma cell lines: Caov3 and ovarian adenocarcinoma, ascites cell line: SKOV3 | MicroRNA expression profiling and validation, bioinformatics analysis, quantitative real-time PCR, cell viability, migration, and invasion assays | It was done using the Kruskal-Wallis and LIMMA statistical tests, Student’s t-test with a statistical significance of p-value <0.05. |
| Minopoli et al. 2019 [14] | Histopathological study | Tissue samples of 42 patients with different subtypes of epithelial ovarian cancer Human ovarian carcinoma cell line: SKOV-3, A2780 | Tissue microarray building, Immunohistochemistry, Flow cytometry, the culture of mesothelial cells, Western blot, adhesion of epithelial ovarian cancer (EOC) cells onto extracellular matrix proteins, adhesion and invasion assay, fluorescence microscopy, ligand binding assay. | Done using one-way ANOVA and post hoc Dunnett t-test, Pearson's chi-square test with a statistical significance of p-value <0.05. |
| Zhang et al. 2019 [5] | Histopathological study | Ninety-one formalin-fixed and paraffin-embedded tissue samples from patients with high-grade serous adenocarcinoma Ovarian cancer cell line: A2780 | Immunohistochemistry, Western blot analysis, RT-PCR, transwell migration assay | Done with unpaired Student’s t-test, Pearson's correlation analysis. Statistical significance of p-value <0.05. |