microRNA‐based diagnostic and therapeutic applications in cancer medicine

miR-34a Tissue (TMA) LNA ISH Bladder Population-based (n = 229) Prognostic value of epithelial cell expression Andrew et al. (2014) miR-21 Tissue (TMA) LNA ISH Bladder Testing (n = 232) Prognostic value of both epithelial and stroma cell expression in urothelial carcinoma (80% of the bladder) Ohno et al. (2016) miR-222 Tissue (Frozen) RT-qPCR Bladder Testing (n = 387) Diagnostic value for separating from malignant from normal tissue and prognostic value Tsikrika et al. (2018) miR-658,-762,-4281,-4649-5p,-4665-3p,-4736,-6836-3p Blood (Serum) 3D-Gene® Human miRNA Oligo Chip Bone and soft tissue Discovery (n = 161), training (n = 276), validation (n = 356) Diagnostic value of miRNA signature for early disease detection (sarcomas) and for separating malignant tumors from benign conditions Asano et al. (2019) miR-1908 Tissue (Frozen) RT-qPCR Bone Testing (n = 424) Prognostic value in osteosarcoma Lian et al. (2016) miR-1915-3p,-3679-5p,-4763-3p Blood (Serum) 3D-Gene® Human miRNA Oligo Chip Brain Training (n = 300), validation (n = 280) Diagnostic value of miRNA signature for early disease detection (diffuse glioma) Ohno et al. (2019) miR-1246,-1307-3p,-1364,-6861-5p,-6875-5p Blood (Serum) 3D-Gene® Human miRNA Oligo Chip Breast Training (n = 2081), validation (n = 2549) Diagnostic value of miRNA signature for early disease detection Shimomura et al. (2016) let-7b-5p,miR-16-5p,-19a-3p,-19b-3p,-20a-5p,-25-3p,-92a-3p,-93-5p,-106a-5p,-223-3p,-425-5p,-451a Blood (Serum) qRT-PCR Breast Discovery (n = 48), training (n = 64), testing (n = 246), validation (n = 72) Diagnostic value of miRNA signature for early disease detection Zou, Xia, et al. (2020) miR-629-3p,-4710 Blood (Serum) 3D-Gene® Human miRNA Oligo Chip Breast Training (n = 460) and validation (n = 461) Diagnostic value of miRNA signature in combination with clinicopathological factors for detection of lymph node metastasis Shiino et al. (2019) miR-26a-5p,-29c-3p,-29c-5p,-30b-5p,-148a-3p,-361-3p,-645,-652-5p,-934 Tissue (FFPE) qRT-PCR Breast Training (n = 318), testing (n = 318), validation (n = 204) Diagnostic value of miRNA signature in combination with clinicopathological factors for detection of lymph node metastasis Xie et al. (2018) miR-21,-96,-139,-141,-145,-182,-183,-200a,-429 Tissue (TCGA) Bioinformatics (RNAseq) Breast TCGA data (n = 1214) Diagnostic value of miRNA signature for early disease detection and for separating malignant tumors from normal tissue Xiong et al. (2017) miR-24-3p Blood (Plasma), Tissue (TCGA) Nanostring, Bioinformatics (miRNAseq) Breast Testing (n = 230), TCGA validation (n = 1024) Prognostic value and predictive value of metastatic disease Khodadadi-Jamayran et al. (2018) miR-21 Tissue (TMA) LNA ISH Breast Validation (n = 901) Prognostic value of tumor-associated fibroblast expression based on ER/PR/HER2 tumor classification MacKenzie et al. (2014) Let-7b Tissue (TMA) LNA ISH Breast Population-based (n = 2033) Prognostic value of epithelial cell expression based on ER/PR/HER2 tumor classification Quesne et al. (2012) miR-148b-3p,-190b,-429 Tissue (TCGA) Bioinformatics (miRNAseq) Breast TCGA data (n = 1187) Prognostic value of miRNA signature Dai et al. (2019) miR-205 Tissue, TMA LNA ISH Breast Population-based (n = 1686) Prognostic value of epithelial cell expression based on histological tumor classification Quesne et al. (2012) miR-210 Tissue, Frozen TaqMan RT-qPCR Breast Validation (n = 219) Prognostic value of miRNA expression Camps et al. (2008) miR-221 Tissue ISH Breast Validation (n = 377) Prognostic value of epithelial cell expression Hanna, Wimberly, et al. (2012) miR-301 Tissue (TMA, TCGA/METABRIC) LNA ISH, bioinformatics (miRNAseq, microarrays) Breast Testing (n = 380), TCGA validation (n = 634), METABRIC validation (n = 1262) Prognostic value of epithelial cell expression Zheng, Huang, et al. (2018) miR-493 Tissue, TMA LNA ISH Breast Validation (n = 382) Prognostic value of epithelial expression in triple negative breast cancer Yao et al. (2018) miR-145,-200c,-218 Tissue, TCGA Bioinformatics Cervix Validation (n = 254) Prognostic value of miRNA signature Liang et al. (2017) miR-144, −200b-3p,-451 Stool RT-qPCR Colon, rectum Training (n = 60), testing (n = 175) Diagnostic value of erythrocyte-specific miRNAs in the normalizer for early disease detection as a modified fecal occult blood test. Wu et al. (2017) miR-18a,-221 Stool TaqMan RT-qPCR Colon, rectum Testing (n = 595) Diagnostic value of miRNA signature for early disease detection Yau et al. (2014) miR-21,-320,-498 Tissue TaqMan RT-qPCR Colon, rectum Testing (n = 224) Prognostic value of miRNA signature Bahnassy et al. (2018) miR-10b Tissue (Frozen/FFPE) RT-qPCR Colon, rectum Testing (n = 492) Prognostic value and predictive value of metastatic disease Jiang et al. (2016) miR-21 Tissue, FFPE LNA ISH Colon, rectum Population-based (n = 764) Prognostic value of tumor-associated fibroblast expression Kjaer-Frifeldt et al. (2012) miR-21 Tissue, TMA LNA ISH Colon, rectum Population-based (n = 277) Prognostic value of tumor-associated fibroblast expression Kang et al. (2015) miR-181c Tissue (Frozen, FFPE) TaqMan RT-qPCR Colon, rectum Discovery (n = 10), training (n = 80 × 2[matched Frozen and FFPE]), validation (n = 57) Concordant prognostic value in frozen and FFPE tumor tissues of stage II cases Yamazaki et al. (2017) let-7a-2, miR-32,-181a-1, -197,-328,-505,-652 Tissue (TCGA) Bioinformatics (RNAseq) Colon, rectum TCGA data (n = 337) Prognostic value of miRNA signature Xu et al. (2017) miR-99a,-137,-499a,-548k,-654,-3619,-3170 Tissue (TCGA) Bioinformatics (miRNAseq) Head and Neck TCGA data (n = 569) Prognostic value of miRNA signature in head and neck squamous cell carcinoma Lu et al. (2019) let-7b-5p, miR-24-3p,-140-3p,-192-5p,-223-3p Blood, Serum RT-qPCR Nasopharyngeal Discovery (n = 60), testing (n = 304), validation (n = 82) Diagnostic value of miRNA signature for early disease detection Zou, Zhu, et al. (2020) miR-20a-5p,-25-3p,-30a-5p,-92a-3p,-132-3p,-185-5p,-320a,-324-3p Blood (Plasma) TaqMan RT-qPCR Liver Training (n = 85), testing (n = 64), validation (n = 149) Diagnostic value of miRNA signature for early disease detection Wen, Han, et al. (2015) miR-21 Blood (Serum) RT-qPCR Liver Training (n = 80), validation (n = 453) Diagnostic value of miRNA signature for early disease detection Guo et al. (2017) miR-26a,-26b Tissue (FFPE) Multiplex RT-qPCR Liver Training (n = 129), testing (n = 119) Predictive value of treatment response to interpheron-alpha Ji et al. (2013) miR-101-3p,-101-5p Tissue (TCGA) Bioinformatics (miRNAseq) Liver TCGA data (n = 414) Diagnostic value for early disease detection and for separating hepatocellular carcinoma from normal liver tissue Yang, Pang, et al. (2018) miR-10b,-195 Tissue (TCGA, GEO datasets) Bioinformatics (miRNAseq, microarrays) Liver TCGA data (n = 421), GEO datasets (n = 803) Prognostic value of miRNA signature Nagy et al. (2018)) miR-17-5p Blood, Serum RT-qPCR Lung Validation (n = 275) Diagnostic value for early disease detection and prognostic value Chen et al. (2013) miR-20a,-24,-25,-145,-152,-199a-5p,-221,-222,-223,-320 Blood, Serum TaqMan RT-qPCR Lung Training (n = 310), validation (n = 310) Diagnostic value of miRNA signature for early disease detection Chen et al. (2012) miR-21 Tissue, TMA LNA ISH Lung Validation (n = 335) Prognostic value of tumor-associated fibroblast and epithelial cell expression Stenvold, Donnem, Andersen, Al-Saad, Valkov, et al. (2014) miR-21-5p,-30d-5p Tissue (TCGA, GEO datasets) Integrated bioinformatics Lung Training (n = 2251), TCGA validation (n = 423) Prognostic value of miRNA signature Li et al. (2017) miR-451 Blood (Plasma) 3D-Gene® Human miRNA Oligo Chip Lung Discovery (n = 6), validation (n = 309) Prognostic value of exosomal miRNA levels Kanaoka et al. (2018) miR-126 Tissue LNA ISH Lung Validation (n = 312) Prognostic value of epithelial cell expression Donnem et al. (2011) miR-143,-145 Tissue, TMA LNA ISH Lung Validation (n = 553) Sex-specific prognostic value of stromal expression (miR-143 in females and miR-145 in males) Skjefstad et al. (2018) miR-155 Tissue, TMA LNA ISH Lung Validation (n = 320) Prognostic value of epithelial cell expression Donnem et al. (2011) miR-182 Tissue, TMA LNA ISH Lung Validation (n = 305) Prognostic value of epithelial cell expression Stenvold, Donnem, Andersen, Al-Saad, Busund, et al. (2014) miR-205 Tissue, Blood Meta-analysis Lung Aggregate (n = 1231) Diagnostic value for separating malignant tumors from normal lung tissue Li, Sun, et al. (2017) miR-205 Tissue, Blood Meta-analysis Lung Aggregate (n = 756) Prognostic value

Li, Sun, et al. (2017)

miR-210 Tissue, TMA LNA ISH Lung Validation (n = 259) Prognostic value of stromal cell expression Eilertsen et al. (2020) miR-873,-1293,-1914 Tissue (TCGA) Bioinformatics (miRNAseq) Lung TCGA data (n = 528) Prognostic value of miRNA signature in lung adenocarcinoma Zheng, Mao, et al. (2018) miR-10b Blood (PBMC) RT-qPCR Lung Testing (n = 393) Prognostic and predictive value of treatment response to chemotherapy Yang, Wang, et al. (2018) miR-16,-17,-20a,-21,-29b,-32,-101,-125b,-155-5p,-181,-196a,-204,-372,-373,-455-5p,-1246 Tissue (FFPE, Frozen Meta-analysis Mouth Aggregate (n = 1200) Prognostic value of miRNA signature in oral squamous cell carcinoma Troiano et al. (2018) miR-744-5p,-3196,-6794-5p,-6799-5p,-6820-5p,-8073 Blood, Serum 3D-Gene® Human miRNA Oligo Chip Esophagus Training (n = 566), validation (n = 4965) Diagnostic value of miRNA signature for early disease detection Sudo et al. (2019) miR-18a,-20b,-106a,-223-3p,-486-5p,-584 Blood (Plasma) RT-qPCR Esophagus Discovery (n = 30), training (n = 84), testing (n = 214), validation (n = 99) Diagnostic value of miRNA signature in exosomes for early disease detection Zhou et al. (2017) miR-375 Tissue, TMA LNA ISH Esophagus Validation (n = 249) Prognostic value of epithelial cell expression Li et al. (2013) miR-27-3p Blood (PBMC) TaqMan RT-qPCR Pancreas Discovery (n = 60) and validation (n = 292) Diagnostic value of miRNA expression in PBMCs in combination with CA-19-9 in serum for early disease detection Wang et al. (2013) let-7b-5p,miR-19a-3p,-19b-3p,-25-3p,-192-5p,-223-3p Blood, Serum RT-qPCR Pancreas Training (n = 72), testing (n = 164), validation (n = 60) Diagnostic value of miRNA signature for early disease detection Zou et al. (2019) miR-24,-130b,-135b,-148a,-196 Tissue (FFPE, FNA) RT-qPCR Pancreas Training (n = 95), validation (n = 228) Diagnostic value of miRNA signature for separating PDAC from chronic pancreatitis and benign conditions Brand et al. (2014) miR-182-5p,-375-3p Blood (Plasma) RT-qPCR Prostate Training (n = 113), validation (n = 304) Diagnostic value for early disease detection and prognostic value Bidarra et al. (2019) miR-27a-3p,-29b-3p,-4286 Blood (Serum) RT-qPCR Prostate Training (n = 155), validation (n = 100) Diagnostic value of miRNA signature in combination with clinicopathological factors for early disease detection Lyu et al. (2019) miR-148,-375 Urine TaqMan RT-qPCR Prostate Training (n = 166), testing (n = 134) Diagnostic value for early disease detection in combination with PSA levels Stuopelyte et al. (2016) miR-21 Tissue (TMA) LNA ISH Prostate Validation (n = 478) Prognostic value of stromal cell expression Melbo-Jorgensen et al. (2014) miR-182 Tissue (TMA) Prostate Validation (n = 461) Prognostic value of epithelial cell expression Baumann et al. (2019) let-7i-3p,miR-30d-3p,-106a-5p,-133a-3p, -185-5p,-210-3p, -221-3p,-222-3p, -615-3p Tissue (FFPE,TCGA) RT-qPCR, bioinformatics (miRNAseq) Prostate Training (n = 198), validation (n = 159), TCGA validation (n = 350) Prognostic value of miRNA signature in combination with DNA methylation status of AOX1, COL4A6, and PROM1 in prostate cancer Strand et al. (2019) miR-205 Tissue (TMA) LNA ISH Skin Validation (n = 297) Prognostic value of melanoma cell expression Hanna, Hahn, et al. (2012) miR-15b-5p,-16-5p,-150-5p,-374b-3p Tissue (FFPE) RT-qPCR Skin Training (n = 92), testing (n = 119), validation (n = 45) Prognostic value and predictive value for metastatic disease Hanniford et al. (2015) miR-25 Blood (serum) RT-qPCR Stomach Testing (n = 318) Diagnostic and value for early disease detection and prognostic value Kong et al. (

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