Table 2.

Small extracellular vesicle protein biomarkers, including post-translational modifications, identified in breast cancer diagnosis, prognosis, chemoresistance

Biomarker	Source	Purpose	Expression	Feature	Technology	Reference
EDIL3	Cells	Diagnosis	↑	Related to invasion ability	LC–MS/MS	[147]
FN	Cells/plasma	Diagnosis	↑	Highest expression in ER− BC followed by ER+ and healthy control	LC–MS/MS	[40, 148]
FAK	Plasma	Diagnosis	↑	N/A	RPPA	[40]
MEK1	Plasma	Diagnosis	↑	N/A	RPPA	[40]
CD47	Serum	Diagnosis	↓	N/A	Micro FCM	[149]
GPC-1	Cells	Diagnosis	↑	Located on cell surface, related to proliferation	Nano-LC–MS/MS Sandwich cantilever assay	[98, 150]
GLUT-1	Cells	Diagnosis	↑	Located on the cell surface related to BC migration	Nano-LC–MS/MS	[98]
ADAM10	Cells	Diagnosis	↑	Located on the cell surface	Nano-LC–MS/MS	[98]
EpCAM	Cells/plasma	Diagnosis	↑	Overexpressed in various cancers Diagnosis for HER2+ BC	Microfluidic chips SERS nanotags DNA aptamers mediated- microfluidic	[151–153]
HER2	Cells/plasma	Diagnosis Chemoresistance	↑	Diagnosis for HER2+ BC Related to trastuzumab resistance	Microfluidic chips SERS nanotags DNA aptamers mediated- microfluidic nano-ultra-HPLC–MS/MS	[151–153, 161, 162]
RALGAPA2, PKG1 & TJP2	Plasma	Diagnosis	↑	Phosphoproteins	LC–MS/MS PRM	[145]
LY6G6F, VWF, BSG, C1QA & ANGPT1/Ang1	Plasma	Diagnosis	↑	Glycoproteins	LC–MS/MS	[177]
Glycoprotein 130	Cells	Diagnosis	↑	Glycoprotein	WB	[179]
CD147	Serum	Diagnosis	↑	Glycoprotein	LC–MS/MS WB	[178]
Annexin A2	Cells/serum	Prognosis	↑	Related to poor survival of BC	MALDI-TOF MS	[154, 155]
NGF	Serum	Prognosis	↑	Related to poor survival of BC who undergo neoadjuvant chemotherapy	ProcartaPlex immune-related panels	[156]
IGFRβ	Plasma	Prognosis	↑	Higher expression in later-stage BC	RPPA	[40]
CD82	Serum	Prognosis	↑	Higher expression in later-stage BC	ELISA	[157]
Del-1	Plasma	Prognosis	↑	N/A	LC–MS/MS ELISA	[158]
Survivin	Serum	Prognosis	↑	High expressed in early-stage BC and TNBC Survivin splice variants negatively correlated with tumour grade	ELISA WB	[159]
MMP-1/CD63	Urine	Prognosis	↑	Higher expression in early-stage BC	WB	[160]
PERP, ITB1, GNAS2 & GNA13	Cells/plasma	Chemoresistance	↓	Higher expressed in HER2+ and trastuzumab-sensitive BC	LC–MS/MS	[163]
GSTP1	Cells/serum	Chemoresistance	↑	Higher expressed in adriamycin-resistance BC	FCM WB	[164]
UCHL-1	Cells/serum	Chemoresistance	↑	Higher expressed in adriamycin-resistance BC	FCM WB	[165]
TrpC5	Cells/serum	Chemoresistance	↑	Higher expressed in adriamycin-resistance BC	FCM RT-PCR	[166]
BCRP	Plasma	Chemoresistance	↑	Higher expressed in TEC therapy resistance BC	FCM RT-PCR	[167]
Annexin 6	Cells	Chemoresistance	↑	Higher expressed in gemcitabine resistance BC	Isobaric peptide labelling LC–MS/MS, WB	[168]
ATPases, annexins, tubulins, integrins & Rabs	Cells	Chemoresistance	↑	Higher expressed in TIS cells	LC–MS/MS WB	[170]
P-gp, CD44, galectin-3 & glycogenin-1	Cells	Chemoresistance	↑	Glycoproteins PTX chemotherapy-resistance in TNBC	LC–MS/MS	[170, 180]

Abbreviations: BC Breast cancer, ELISA Enzyme-linked immunosorbent assay, ER Estrogen receptor, FCM Flow cytometry, LC–MS/MS Liquid chromatography with tandem mass spectrometry, N/A Not applicable, PRM Parallel-reaction monitoring, PTX Paclitaxel, RPPA Reverse phase protein microarray, RT-PCR Reverse transcriptase-polymerase chain reaction, SERS Surface enhanced Raman scattering, TEC The anthracycline-taxane-based neoadjuvant chemotherapy (docetaxel, epirubicin, and cyclophosphamide), TIS Therapeutic induced senescent, TNBC Triple negative breast cancer, UHPLC Ultra-high performance liquid chromatography, WB Western blotting