Table 1.
Studies included in the systematic review.
| Author, year, [ref] | Aim of the study | Number of patients | Stage | HPV genotype | Therapy | Biological matrix | Technique/s used | Validation of the results | Most important findings | Response definition |
|---|---|---|---|---|---|---|---|---|---|---|
| miRNA expression in cervical cancer and chemotherapy + radiotherapy | ||||||||||
| Fekete et al., 2020 (24) | To identify predictive miRNAs in platinum-treated SCC | n = 94 SCCs (from GDC data portal): n = 16 non-responders vs. n = 78 responders | Unknown | NE | Platinum-based chemo | T | MiRNA-seq | \ | ↑ let-7g, miR-150, miR-155, miR-342, miR-378a, miR-378c, miR-378d-2, miR-502, miR-5586, miR-7702 in responders vs. in non-responders | Response defined based on disease progression at 18 months. |
| Liu et al., 2018 (25) |
To define the role of miR-492 in SCC | -discovery cohort (n = 6: n = 3 sensitive vs. n = 3 resistant pts) - validation cohort (n = 104 CCs: n = 78 sensitive vs. n = 26 resistant pts) |
n = 57: stage IIb, n = 47: stage IIIb |
NE | Platinum-based chemo + radio | T | RT-PCR based approach (TaqMan Array and assay) | Y - In pts - In cell models - In animal models |
↑ miR-492 in sensitive vs. resistant pts ↑ associated with LNM |
Resistance defined after 12 months after completion of first-line therapy |
| Pedroza-Torres et al., 2016 (26) | To identify a set of miRNAs to predict the response in locally advanced CC pts receiving radiation and chemotherapy treatment. | n = 41 CCs: -discovery cohort (n = 10: n = 5 NR vs. n = 5 CR) - validation cohort (n = 31: n = 15 NR vs. n = 16 CR) |
IIb/IIIb | E | Platinum-based chemo + radio | T | RT-PCR based approach (miScript miRNA PCR Array and Taqman assay) | Y In pts |
↓ miR-100-5p, miR-125a-5p, miR-125b-5p, miR-200a-5p, miR-342 in NR vs. CR.↑ miR-31-3p, miR-3676 in NR vs CR. 7 miRNAs signature associated with DFS | Response evaluated through the RECIST criteria and computed axial tomography scans |
| Fan et al., 2016 (27) | To study the relationship between miR-125a and resistance in CC | n = 43 CCs: n = 23 responders vs. n = 20 non-responders |
n = 21: stage I/II, n = 22: stage III/IV |
NE | Taxol and platinum-based chemo | T | Microarray and RT-PCR | Y - In pts - In cell models - animal models |
↓ miR-125a in non-responders vs. responders ↓ miR-125a: ↓ PFS, OS, Response Rate |
Response defined according the RECIST criteria |
| Chen et al., 2014 (28) | To clarify the role of miR-181a in regulating the chemoresistance of CC | n = 18 SCCs: n = 7 resistant vs. n = 11 sensitive pts |
n = 18: stage IIIB | NE | Platinum-based chemo + radio | T | RT-PCR | Y - In cell models - In animal models |
↑ miR-181a in resistant vs. in sensitive pts | Resistance defined as described by Ke et al. (29) |
| Ke et al., 2013 (29) | To define the roles of miR-181a in determining sensitivity of CC to radiation therapy | n = 18 SCCs: n = 7 resistant vs. n = 11 sensitive pts |
n = 18: stage IIIB | NE | Platinum-based chemo + radio | T | Microarray and RT-PCR | Y - In the same cohort - In cell models - In animal models |
↑ miR-181a in resistant vs. in sensitive pts | Resistance defined based on histological finding of residual tumor cells in the cervical biopsies sampled 6 months after completion of radiotherapy |
| miRNAs expression in cervical cancer and radiotherapy | ||||||||||
| Wei et al., 2020 (30) | To understand the role of miR-411 in radiotherapy response | n = 141 CCs: n = 92 responders vs. 49 non responders |
n = 55: stage I, n = 62: stage II, n = 24: stage III | E | Radio | T/PB | RT-PCR | Y In cell models |
↑ miR-411 in responders vs. in non-responders in both tissue and blood ↑ miR-411 associated with higher OS and PFS |
Efficacy defined according to the RECIST criteria |
| Gao et al., 2019 (31) | To investigate the biological role of GAS5 in the radiosensitivity | n = 20 CCs: n = 9 resistant vs. n = 11 sensitive pts |
IIb to IVb | NE | Radio | T | RT-PCR | Y -In cell models -In animal models |
↑ miR-106b in resistant vs. in sensitive pts | Response defined according to the histological results of residual tumor cells in cervical biopsy samples 6 months after completion of radiotherapy |
| Wei et al., 2017 (32) | To evaluate miR-145 in CCs and investigate its biomarker potential | n = 120 CCs: n = 68 CR vs. n = 52 IR |
n = 77: stage I–II; n = 43: stage III |
E | Radio | P | RT-PCR | N | ↑ miR-145 in CR than in IR pts | Response defined at 6 months after radical radiotherapy |
| Liu et al., 2015 (33) | To examine the role of miR-18a in regulating the radiosensitivity of CC | n = 48 CCs: n = 20 resistant vs. n = 28 sensitive pts |
n = 34: stage I–IIb, n = 14: stage IIIa–Iv | NE | Radio | T | RT-PCR | Y In cell models |
↑ miR-18a in sensitive vs. resistant |
|
| Song et al., 2015 (34) | To explore the association between miR-375 and radioresistance in HR-HPV (+) CC | n = 22 CCs: n = 13 resistant vs. n = 9 sensitive pts |
Ia/Ia2 | E | Radio | T/S | RT-PCR | Y In cell models |
↓ miR-375 in resistant vs. in sensitive | Resistance assessed by histological examination of residual tumor tissues 6 months after completion of radiotherapy |
| miRNA expression in cervical cancer and neoadjuvant treatment | ||||||||||
| Chen et al., 2014 (35) | To investigate the role of miR-143 expression in cervical SCC | n = 24 SCCs with and without NAC therapy (from a total cohort of 77 CCs and 20 normal cervix tissue) | n = 13. Stage Ib2, n = 9: stage IIa, n = 2: stage IIb | E | Taxol and platinum-based chemo | T | RT-PCR | / | ↑ miR-143 after NAC |
According to the WHO criteria * |
| Sun et al., 2013 (36) | To examine the hypothesis that NAC improves prognosis and outcomes after LRH | n = 21 CCs: n = 10 LHR vs. n = 11 NAC+LHR |
IIb | E | Taxol and platinum-based chemo | T | RT-PCR | Y In cell models |
↑ miR-34a, miR-605 in NAC treated vs. NAC non-treated treated pts | Response defined according to the WHO criteria * |
*Complete remission (tumor completely disappeared); partial remission (tumor size decreased more than 50%); stable or no change (tumor size increased or decreased no more than 25%), progression (new lesions or tumor size increased more than 25% during the treatment).
CC, cervical cancer; chemo, chemotherapy; CR, complete response; E, evaluated; HPV, human papillomavirus; HR, high-risk; IR, incomplete response; LRH, laparoscopical radical hysterectomy; NAC, neoadjuvant chemotherapy; NR, no response; Y, yes; N, no; NE, not evaluated; P, plasma; PB, peripheral blood; pts, patients; S, serum; SCC, squamous cell carcinoma; radio, radiotherapy; T, tissue; ↑, higher; ↓, lower; +, positive.