Circulating and Endometrial Tissue microRNA Markers Associated with Endometrial Cancer Diagnosis, Prognosis, and Response to Treatment
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
3. Results
3.1. Diagnostic and Classificatory Capacity of miRs for EC
3.1.1. miRs Studied in Plasma
3.1.2. Serum miRs
3.1.3. miRs Studied in Endometrial Tissue
Tissue miRs with Diagnostic Usefulness for EC
Endometrial miRs Expressed According to Specific EC Chronological Stage
Tissue miRs Associated with EC, Tumor Grade, and Their Transcriptional Targets
Tissue miRs Associated with the EC Histological Types
3.2. miRs and EC Prognosis
3.3. Treatment Response
3.3.1. Mechanisms of Chemoresistance in EC
3.3.2. miRs Involved with Treatment Response in EC
4. Conclusions
Gaps and Opportunity Areas for the Use of miRs as Markers with Clinical Value in EC
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristics | POLE-Mutant | MSI | p53wt/NSMP | p53 Abnormal (CN High) |
---|---|---|---|---|
Mutational frequency | >100 mutations/Mb | 100–10 mutations/Mb | <10 mutations/Mb | <10 mutations/Mb |
Somatic CN alterations | Very low | Low | Low | High |
Top five recurrent gene mutations (%) | POLE (100%) DMD (100%) CSMD1 (100%) FAT4 (100%) PTEN (94%) | PTEN (88%) PIK3CA (54%) PIK3R1 (42%) RPL22 (37%) ARID1A (37%) | PTEN (77%) PIK3CA (53%) CTNNB1 (52%) ARID1A (42%) PIK3R1 (33%) | TP53 (92%) PIK3CA (47%) FBXW7 (22%) PPP2R1A (22%) PTEN (10%) |
Associated histological feature | Endometrioid Grade 3 Broad front invasion TILs Giant tumoral cells | Endometrioid Grade 3 LVSI substantial MELF-type invasion TILs | Endometrioid Grade 1–2 Squamous differentiation ER/PR expression | Serous Grade 3 LVSI High cytonuclear atypia Slit-like spaces |
Associated clinical features | Lower BMI Early Stage (IA/IB) Early onset | Higher BMI Lynch Syndrome | Higher BMI | Lower BMI Advanced stage Late onset |
Prognosis in early stage (I–II) | Excellent | Intermediate | Excellent/intermediate/poor | Poor |
Diagnostic test | NGS (exons 9, 13, 14 or 9–14) Tumor mutation burden | MMR-IHC (MLH1, MSH2, MSH6, PMS2) MSI assay Tumor mutation burden | p53-IHC NGS |
Risk Group | Molecular Classification Unknown | Molecular Classification Known |
---|---|---|
Low |
|
|
Intermediate |
|
|
High-intermediate |
|
|
High |
|
|
Advanced metastatic |
|
|
miR | Function in EC | Sample | Expression | Target Genes | Clinical Value | Reference |
---|---|---|---|---|---|---|
hsa-miR-143-3p | Tumor-suppressive factor by regulating tumorigenesis and progression. | Serum | Up | MAPK1 | Diagnosis | [25] |
hsa-miR-143-3p | Might inhibit cell proliferation, metastasis, and promote the apoptosis of EC cells. | ET | Down | MAPK1 | Prognosis | [88] |
hsa-miR-423 | Inhibit cisplatin-induced apoptosis from decreasing the sensitivity of EC. | EC cell lines: HEC-1B and Ishikawa cells | Up | Bcl-2, Caspase 3/7 | Treatment response | [89] |
hsa-miR-142-3p | Mediation of cell apoptosis by the miR-142-3p-FAM98A signaling pathway (anti-apoptotic and pro-proliferative effects). | Plasma | Up | FAM98A | Diagnosis | [22,23] |
hsa-miR-146a-5p | Attenuates the effect of NIFK-AS1 on M2 polarization inhibition of macrophages and estrogen-induced EC cell proliferation, migration, and invasion. | Plasma | Up | NIFK-AS1 | Diagnosis | [22,24] |
hsa-miR-151a-5p * | Induce proliferation, migration, and partial epithelial metastasis. | Plasma | Up | E-cadherin Fibronectin SNAI2 | Diagnosis | [22,90] |
hsa-miR-195-5p | Suppressing cell migration, proliferation, and promote apoptosis. | Serum | Up | PI3K/AKT and MAPK/ ERK pathways FGFR1, FGF2 | Diagnosis | [25,26,27] |
hsa-miR-20b-5p | VEGFA transcription. | Serum | Up | HIF1A PTEN STAT3 | Diagnosis | [28,29,30,31,32,33,34,35,36,37] |
hsa-miR-204 | Mediates the migration and invasion of EC by regulating FOXC1. | - Serum - EC cell lines: HEC1A, HEC1B, AN3CA, KLE, RL95 - ET | Up | FOXC1 | Diagnosis | [38,39] |
hsa-miR-484 * | Tumor suppressor. | MCF7 and T-47D cells | Down | KLF4 | Treatment response | [91] |
hsa-miR-499 | Suppressed tumor growth and angiogenesis. | ET | Up/Down | VAV3 | Diagnosis | [20,92] |
hsa-miR-135b | Promotes proliferation of EC cells. | ET | Up | FOXO1 | Diagnosis | [20,93] |
hsa-miR-205 | Tumor suppressor through the inhibition of EMT. | ET | Up | PTEN | Prognosis | [94,95] |
hsa-miR-10b | Inhibits apoptosis and promotes proliferation, migration, and invasion of EC cells. | ET | Down | HOXB3 | Diagnosis | [96] |
hsa-miR-195 | Inhibits migration, invasion and EMT. | - ET - AN3-CA and Hec1A cells | Down | SOX4 GPER or GPR30 | Diagnosis | [97,98] |
hsa-miR-30a-5p * | Inhibits cell proliferation and migration. | ET | Down | UBE3C | Diagnosis | [99] |
hsa-miR-30a-3p | Modulate autophagy. | ET | Down | BECN1 | Diagnosis | [20,100] |
hsa-miR-let 7a | Inhibits the growth of EC cells. | - ET - HeLa cells | Down | AURKB | Diagnosis | [101] |
hsa-miR-221 | Act similar to a critical site of the regulatory pathway ERα/HIF1-α/SNAI2. | ET | Up/Down | LMOD1 ERα MDM2 | Diagnosis | [41,102] |
hsa-miR-193 * | Enhance cell invasion-mediated EMT and improve cell proliferation through the ING5/PI3K/AKT signal pathway. | ET | Up/Down | RAMP1 ING5 | Diagnosis | [41,103] |
hsa-miR-152 | Inhibits proliferation of EC cells via inducing G2/M phase arrest by suppressing CDC25B expression. | - ET - KLE and HEC-1B cells | Down | ENPP2 SNCAIP CDC25B | Diagnosis | [41,104] |
hsa-miR-30c | Modulates MTA1, which may promote EC progression through the AKT/mTOR/4E-BP1 pathway. | - ET - EC cell lines: Ishikawa, HEC-1B, and RL-952 | Down | GPRASP2 MTA1 | Prognosis | [41,105] |
hsa-miR-185 * | Inhibited EMT by targeting Rab25 expression. | ET | Up | KLF2 Rab25 | Diagnosis | [41,106] |
hsa-miR-106a | Acts as an oncogenic miR in EC by inhibiting tumor suppressor BCL2L11 expression. | ET | Up | TGFB1I1 BCL2L11 | Diagnosis | [41,107] |
hsa-miR-181a | Acts as an oncogenic miR that negatively regulate tumor suppressor PTEN. | ET | Up | PTEN DPP6 | Diagnosis | [41,108] |
hsa-miR-210 | Promoted the progression of EC by negative regulation NFIX expression. | ET | Up | ENPP2 C2orf32 NFIX | Diagnosis/Prognosis | [41,109] |
hsa-miR-103 | - Regulates the progression in EC through ZO-1. - Regulates the growth and invasion of EC cells through the downregulation of TIMP-3 | - ET - Cell lines: HEC-1B and Ishikawa | Up | ZO-1 TIMP-3 | Diagnosis/Prognosis | [110,111] |
hsa-miR-let 7c | Contributes to paclitaxel resistance via Aurora-B in SEC. | SEC cell lines: USPC1, USPC1-PTXR, USPC1-PTXR2 | Down | Aurora-B | Treatment response | [112] |
hsa-miR-200c | - It is speculated that the increase in cell proliferation is mediated through repression of KLF9. - Regulated the translocation of β-catenin from the cytoplasm to the nucleus via inhibition of BRD7, resulting in increased expression of its transcriptional target genes, cyclin D1 and c-myc. | - ET - Cell lines: HEC-1A, Ishikawa | Up | PTEN KLF9 BRD7 | Diagnosis | [42,54,113] |
hsa-miR-183 | Promotes cell proliferation and invasion by targeting MMP-9. | - ET - EC cell lines: KLE, HEC-1-A and HHUA | Up | MMP-9 | Diagnosis | [114] |
hsa-miR-186 | May reduce the expression of tumor suppressor FOXO1 and thereby deregulates cell cycle control. | - Serum - EC cell lines: HEC-1B and Ishikawa | Up | FOXO1 | Diagnosis | [43,115] |
hsa-miR-141-3p | Promoter EC cells proliferation, indicating that could act as an oncogenic miR in EC progression. | - ET - EC cell lines: HEC-1 A and KLE cells | Up | DAPK1 | Prognosis | [116,117] |
hsa-miR-200a | Promotes EMT of EC cells by negatively regulating FOXA2 expression | ET | Up | FOXA2 | Diagnosis | [118] |
hsa-miR-15a-5p | Inhibits the growth of EC cells via attenuating WNT3A expression in the Wnt/β-catenin signaling pathway. | - ET - Cell lines: HEC-251, AN3CA, RL95-2, HEC-1-A, ISK, Ishikawa, and JEC | Down | WNT3A | Diagnosis | [47] |
hsa-miR-449a | Might module the EC progression via negative regulation of transcription from RNA polymerase II promoter | ET | Down | LEF1 | Prognosis | [48] |
hsa-miR-145-5p | Might act as a tumor suppressor and regulate cell cycle associated processes to inhibit the development of EC | ET | Down | SOX11 | Prognosis | [48] |
hsa-miR-505 | Functions as a tumor suppressor by targeting TGF-α | - ET - EC cell lines: HEC-1B and Ishikawa | Down | TGF-α | Diagnosis | [49] |
hsa-miR-589-5p | Inhibits cell proliferation, migration, and invasion by targeting TRIP6. | - ET - EC cell lines: HEC-1B and AN3CA | Down | TRIP6 | Diagnosis | [50] |
hsa-miR-20a-5p | - Inhibits EMT and invasion of EC cells by targeting STAT3 - Inhibits EC progression by targeting Jak1. | - EC cell lines: ECC-1, KLE, HHUA, RL95-2 and Ishikawa - HEK293 cells - Human uterine epithelial cell line HES - ET | Down | STAT3 Jak1 | Diagnosis | [51,52] |
hsa-miR-23b | It may act as a tumor suppressor miR: suppressed the proliferation of Ishikawa cells. | - ET - Ishikawa EC cells | Down | CCNG1 | Prognosis | [46,119] |
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Oropeza-de Lara, S.A.; Garza-Veloz, I.; Berthaud-González, B.; Martinez-Fierro, M.L. Circulating and Endometrial Tissue microRNA Markers Associated with Endometrial Cancer Diagnosis, Prognosis, and Response to Treatment. Cancers 2023, 15, 2686. https://doi.org/10.3390/cancers15102686
Oropeza-de Lara SA, Garza-Veloz I, Berthaud-González B, Martinez-Fierro ML. Circulating and Endometrial Tissue microRNA Markers Associated with Endometrial Cancer Diagnosis, Prognosis, and Response to Treatment. Cancers. 2023; 15(10):2686. https://doi.org/10.3390/cancers15102686
Chicago/Turabian StyleOropeza-de Lara, Sergio Antonio, Idalia Garza-Veloz, Bertha Berthaud-González, and Margarita L. Martinez-Fierro. 2023. "Circulating and Endometrial Tissue microRNA Markers Associated with Endometrial Cancer Diagnosis, Prognosis, and Response to Treatment" Cancers 15, no. 10: 2686. https://doi.org/10.3390/cancers15102686
APA StyleOropeza-de Lara, S. A., Garza-Veloz, I., Berthaud-González, B., & Martinez-Fierro, M. L. (2023). Circulating and Endometrial Tissue microRNA Markers Associated with Endometrial Cancer Diagnosis, Prognosis, and Response to Treatment. Cancers, 15(10), 2686. https://doi.org/10.3390/cancers15102686