36 promising molecules

Gene symbol

a, mRNAs are targeted by multiple miRNAs.

b, mRNAs on manually multiple molecular pathways by KEGG Mapper.

c, mRNAs or miRNAs on the Circos plot based on exosomal molecules and ExBCD Terms (including enriched terms of GOBP, KEGG pathway, filtered OS, and "PB" or "BIM").

Signal Pathway Function Diseases Viral or bacterial infection KEGG pathway ID Reference (PMID) OS (P-value) ExoBCD Tags

PBs,The Potential Biomarkers;
BIMs, The Biologically Interesting Molecules;
pPBs, The Promising Potential Biomarkers;
pBIMs, The promising Biologically Interesting Molecules
mpPBs, The Most Promising Potential Biomarkers
mpBIMs, The Most Biologically Interesting Molecules

IGF1Rabc PI3K-Akt; MAPK; Ras; Rap1; mTOR; HIF-1; Longevity regulating Focal adhesion; Adherens junction; Endocytosis; EGFR tyrosine kinase inhibitor resistance; Signaling pathways regulating pluripotency of stem cells Breast cancer; Hepatocellular carcinoma; Melanoma; Prostate cancer   hsa04510; hsa05218; hsa04010; hsa04151; hsa05205 hsa04015; hsa04014; hsa04144; hsa04550; hsa01521; hsa05224; hsa04520; hsa05215; hsa05225; hsa04066; hsa04150; hsa04211; hsa04213 29152592; 21574055 3.50E-05
mpPBs
FRS2abc MAPK; PI3K-Akt; Ras; mTOR Cell proliferation Breast cancer   hsa04010; hsa04151; hsa04014; hsa05224; hsa05205 27533459; 29156384 1.60E-03
mpPBs
miR-18a-5pc p53; TGF beta Focal adhesion; Cell cycle     hsa04110; hsa04510; hsa05218; hsa04115; hsa04350 29050253; 29988076 9.00E-04
pPBs
miR-195-5pc p53; TGF beta Focal adhesion; Cell cycle Melanoma   hsa04110; hsa04510; hsa05218; hsa04115; hsa04350 29050253; 26309570 1.80E-08
pPBs
miR-223-3pc TGF beta Focal adhesion; Cell cycle     hsa04110; hsa04510; hsa05218; hsa04350 29805680; 31395736 6.00E-04
pPBs
FGFR2bc MAPK; PI3K-Akt; Ras; Rap1 Endocytosis; EGFR tyrosine kinase inhibitor resistance; Regulation of actin cytoskeleton; Signaling pathways regulating pluripotency of stem cells   Gastric cancer; Prostate cancer   hsa04010; hsa04151; hsa04014; hsa04015; hsa04810; hsa04144; hsa01521; hsa05226; hsa04550; hsa05230; hsa05215 24043118; 23527311 3.10E-05
pPBs
LDHAab HIF-1       hsa05230; hsa04066 27598996; 19668225 9.10E-03
pPBs
SFNabc p53 Cell cycle     hsa04110; hsa04115 19452229; 11423985 1.33E-02
pPBs
miR-124-3pc p53; TGF beta Focal adhesion; Cell cycle Melanoma   hsa04110; hsa04510; hsa05218; hsa04115; hsa04350 29050253; 27468577 4.05E-02
pPBs
miR-130a-3pc TGF beta Focal adhesion; Cell cycle Melanoma   hsa04110; hsa04510; hsa05218; hsa04350 29746865; 30510209 2.08E-02
pPBs
miR-17-5pc p53; TGF beta Focal adhesion; Cell cycle Melanoma   hsa04110; hsa04510; hsa05218; hsa04115; hsa04350 29050253; 30989460 2.00E-02
pPBs
miR-29b-3pc p53; TGF beta Focal adhesion; Cell cycle Melanoma   hsa04110; hsa04510; hsa05218; hsa04115; hsa04350 29050253; 31349873 6.50E-06
pPBs
ERBB2ab MAPK; PI3K-Akt; HIF-1 Focal adhesion; Adherens junction; Tight junction; EGFR tyrosine kinase inhibitor resistance Breast cancer; Gastric cancer; Prostate cancer   hsa04510; hsa04010; hsa04151; hsa05205; hsa05226; hsa01521; hsa05224; hsa05230; hsa04520; hsa04530; hsa05215; hsa04066; 29491426; 10632352 3.74E-01
pPBs
FGFR3ab MAPK; PI3K-Akt; Ras; Rap2 Endocytosis; EGFR tyrosine kinase inhibitor resistance; Regulation of actin cytoskeleton; Signaling pathways regulating pluripotency of stem cells     hsa04010; hsa04151; hsa04014; hsa04015; hsa01521; hsa04810; hsa04550; hsa05230 24548884; 21792889 8.29E-01
pPBs
ITGB1ab PI3K-Akt; Rap1 Focal adhesion; Regulation of actin cytoskeleton; Tight junction Arrhythmogenic right ventricular cardiomyopathy (ARVC); Dilated cardiomyopathy (DCM); Hypertrophic cardiomyopathy (HCM) Human papillomavirus; Pathogenic Escherichia coli; Yersinia hsa04510; hsa04151; hsa05205; hsa04015; hsa04810; hsa05165; hsa05135; hsa05130; hsa05410; hsa05412; hsa05414; hsa04530 16452209; 26675717 2.04E-01
pPBs
ITGB7b PI3K-Akt Focal adhesion; Regulation of actin cytoskeleton Arrhythmogenic right ventricular cardiomyopathy (ARVC); Dilated cardiomyopathy (DCM); Hypertrophic cardiomyopathy (HCM) Human papillomavirus infection hsa04151; hsa04810; hsa05165; hsa05410; hsa05412; hsa05414; hsa04510 21474670 5.74E-02
pPBs
NANOGab   Regulating pluripotency of stem cells     hsa05205; hsa04550 22381696; 22528804 3.03E-01
pPBs
PKN2ab PI3K-Akt     Yersinia infection hsa04151; hsa05135 28515445 5.25E-01
pPBs
CD82b p53       hsa04115 30604894; 9736046 NA
pPBs
miR-615-3pc p53; TGF beta Focal adhesion     hsa04510; hsa04115; hsa04350 29501762 1.62E-02
mpBIMs
miR-639c p53 Cell cycle Melanoma   hsa04110; hsa04115; hsa05218 24917697 6.50E-03
mpBIMs
miR-595c TGF beta Endocytosis; Tight junction Melanoma   hsa04350; hsa04144; hsa04530 27133048 1.90E-06
mpBIMs
IL1RAPc MAPK Inflammatory mediator regulation of TRP channels     hsa04010; hsa04750 26261316 4.58E-02
mpBIMs
PIK3R5bc PI3K-Akt; Oxytocin; Phospholipase D       hsa04921; hsa04072; hsa04151 28123587 3.70E-03
mpBIMs
ARF6ab Ras; Phospholipase D Endocytosis   Pathogenic Escherichia coli; Yersinia hsa04014; hsa04144; hsa05135; hsa05130; hsa04072 19416474; 25799492 7.02E-01
pBIMs
BIDb p53     Human cytomegalovirus hsa04115; hsa05163 16874058; 25760094 5.37E-01
pBIMs
CACNB2b MAPK; Oxytocin   Arrhythmogenic right ventricular cardiomyopathy (ARVC); Dilated cardiomyopathy (DCM); Hypertrophic cardiomyopathy (HCM)   hsa04010; hsa05410; hsa05412; hsa05414;  hsa04921 25220184 1.09E-01
pBIMs
CDC42ab MAPK; Ras; Rap1 Focal adhesion; Adherens junction;Tight junction; Endocytosis; Regulation of actin cytoskeleton   Human papillomavirus; Pathogenic Escherichia coli; Yersinia hsa04510; hsa04010; hsa04014; hsa05205; hsa04015; hsa04810; hsa04144; hsa05165; hsa05135; hsa05130; hsa04520; hsa04530 23750283; 24529727 8.39E-01
pBIMs
CHEK2ab p53 Cell cycle     hsa04110; hsa04115 21876083; 26987529 7.43E-01
pBIMs
DUSP1b MAPK       hsa04010 11313879; 21655091 5.24E-02
pBIMs
ELK1ab MAPK; Ras; Oxytocin Focal adhesion Hepatocellular carcinoma Human cytomegalovirus hsa04510; hsa04010; hsa05205; hsa04014; hsa05225; hsa05163; hsa04921 21293856; 29491426 2.38E-01
pBIMs
FGF9ab MAPK; PI3K-Akt; Ras; Rap1 Regulation of actin cytoskeleton Breast cancer; Gastric cancer; Melanoma   hsa05218; hsa04010; hsa04151; hsa04014; hsa04015; hsa04810; hsa05224; hsa05226 21098263; 27166269 9.55E-01
pBIMs
FZD5ab mTOR Signaling pathways regulating pluripotency of stem cells Breast cancer; Gastric cancer; Hepatocellular carcinoma Human papillomavirus hsa05205; hsa05165; hsa04550; hsa05224; hsa05226; hsa05225; hsa04150 27323393 1.32E-01
pBIMs
HTR7ab Ras; Calcium Neuroactive ligand-receptor interaction     hsa04014; hsa04020; hsa04080 22726445 8.18E-01
pBIMs
TSC2b PI3K-Akt; mTOR; p53; Longevity regulating; Phospholipase D     Human cytomegalovirus; Human papillomavirus hsa04115; hsa04151; hsa05165; hsa04072; hsa04150; hsa05163; hsa04211 16537497 1.70E-01
pBIMs
miR-149-3pc TGF beta Focal adhesion; Cell cycle Melanoma   hsa04110; hsa04510; hsa04350; hsa05218 29218245 3.34E-01
pBIMs

Notes:

1) 36 promising molecules, including 25 mRNA molecules without the prefix “mi-” of their gene symbols and 11 miRNAs, were identified by circos plot, manual mapping of multiple molecular pathways, and target relationship.

2) The results in the second, third, and fourth columns were from the enrichment of KEGG mapping, including pathway, function, and disease, respectively. The fifth and sixth columns contain literatures related to breast cancer and overall survival estimation, individually.

3) All molecules were significant in overall survival (OS) analysis (P < 0.05). PMID (PubMed ID) of references with biomarker reporting in breast cancer and the significant OS value (P < 0.05)were underlined.

4) Potential biomarkers (PBs) are mined from original studies on exosomes in breast cancer or rigorously identified from high-throughput expression data;

The promising PBs (pPBs) are selected by the procedure of "Verificational insight into exosomal molecules" (Pipeline) and reported as biomarkers for breast cancer in original studies.

The most promising PBs (mpPBs) are molecules targeted by multiple exosomal miRNAs in breast cancer, reported as biomarkers for breast cancer in original researches and playing key roles in the progress and prognosis of breast cancer.

And the biologically interesting molecules (BIMs), the promising biologically interesting molecules (pBIMs) and the most promising biologically interesting molecules (mpBIMs) may play different important roles in carcinogenesis and cancer development.

5) IGF1R and FRS2, the most promising PBs, being significant in prognosis and reported as biomarkers for breast cancers by multiple original studies, were hub molecules targeted by multiple key miRNAs in cancers being crucial for carcinogenesis and cancer development. And SFN should be also focused on.