Table 1. Basic information of included studies.
Detailed information of the 19 studies we included in our research.
| Years | Authors | Sample size |
Stone composition |
Proteomic technique | Verification methods | Proteins identified | Main findings |
|---|---|---|---|---|---|---|---|
| 2007 (Mushtaq et al., 2007) | Mushtaq et al. | 40 | CaOx | 1D PAGE LC-MS/MS |
Western blot | 4 | Myeloperoxidase, α-defensin and calgranulin were identified from inner core of CaOx stones and they promoted the aggregation of CaOx crystals. Osteopontin was detected both in the inner and outer matrix of CaOx stones. |
| 2008 (Canales et al., 2008) | Canales et al. | 7 | CaOx | LC-MS/MS | NA | 68 | A significant number of inflammatory proteins, such as immunoglobulin, α-defensin-3, clusterin, complement C3a, kininogen, calgranulin and fibrinogen, were found in CaOx stones matrix. |
| 2008 (Merchant et al., 2008) | Merchant et al. | 4 | CaOx | LC-MS/MS | Western blot | 158 | A total of 58 prevalent proteins were detected in at least two of the three LC-MS/MS analyses. Pathway analysis suggested that a significant fraction of CaOx stone matrix proteins participate in inflammatory processes. |
| 2008 (Chen et al., 2008) | Chen et al. | 10 | CaOx | 1D PAGE LC-MS/MS |
NA | 11 | There were abundant proteins with molecular weight around 27, 14, and 10 kDa in CaOx stones matrix. Methylation, deamidation, and oxidation were indentified with mass spectroscopy in these proteins. |
| 2009 (Canales et al., 2009) | Canales et al. | 1 | Matrix stone | LC-MS/MS | NA | 33 | Protein file of matrix stones included many similar inflammatory proteins seen in previous proteomic studies of CaOx stone matrix, indicating a primary inflammatory mechanism behind matrix stones. |
| 2010 (Thurgood & Ryall, 2010) | Thurgood et al.# | 5 | HA | LC-MS/MS | NA | 36 | Binding of proteins to urinary hydroxyapatite, brushite, and uric acid crystals is selective and distinct. Several proteins consistently detected in the healthy urine crystal extracts, such as osteopontin, prothrombin and S100A9, have been previously implicated in kidney stone disease. |
| Brushite | LC-MS/MS | NA | 65 | ||||
| UA | LC-MS/MS | NA | 7 | ||||
| 2010 (Thurgood et al., 2010) | Thurgood et al.# | 5 | COM | LC-MS/MS | 2D SDS-PAGE | 14 | The incorporation of proteins into COM and COD crystals from healthy human urine was selective. Principal proteins in COM crystal extracts were prothrombin fragment 1, S100A9, and IGκV1-5, while those in COD crystals included osteopontin, IGκV1-5, S100A9, annexin A1, HMW kininogen-1, and inter-α-inhibitor. |
| COD | LC-MS/MS | NA | 34 | ||||
| 2010 (Canales et al., 2010) | Canales et al. | 13 | CaOx | LC-MS/MS | NA | 49 | CaOx and CaP stones shared similar matrix proteins associated with inflammatory response, indicating that inflammation play an important role in calcium stone formation, no matter as an origin role or a secondary response. |
| 12 | CaP | LC-MS/MS | NA | 45 | |||
| 2011 (Kaneko et al., 2011) | Kaneko et al. | 1 | UA, COM | LC-MS/MS | NA | 32 | Calcium-binding proteins, such as calprotectin, psoriasin, calprotectin and so on, were identified in stones from patients with hyperuricemia. They may play a significant role in the formation of kidney uric acid stones. |
| 2012 (Jou et al., 2012) | Jou et al. | 5 | UA | LC-MS/MS | Western blot | 242 | The function of proteins identified from uric acid stones is mainly engaged in inflammatory process and lipid metabolism, implying a possible relation between lipotoxicity and stone formation. |
| 2012 (Kaneko et al., 2012) | Kaneko et al. | 17 | CaOx, UA | 1D PAGE LC-MS/MS |
Western blot | 30 | Uromodulin and albumin are often detected in stones. Osteopontin, prothrombin, protein S and protein Z are identified specifically in calcium oxalate stones. Immunoglobin G fragments are detected in uric acid stones. |
| 2013 (Okumura et al., 2013) | Okumura et al. | 9 | CaOx | LC-MS/MS | Western blot | 92 | Prothrombin, osteopontin, S100A8 and S100A9 were found in most stones, some samples had high contents of prothrombin and osteopontin, while others had high contents of calgranulins and neutrophil-enriched proteins. |
| 2014 (Boonla et al., 2014) | Boonla et al. | 16 | COM, UA, MAP | 1D PAGE LC-MS/MS |
Western blot | 62 | Kidney stones greatly contained inflammatory and fibrotic proteins, indicating that inflammation and fibrosis are involved in the formation of stones. S100A8 and fibronectin were the most abundant protein in stone matrix. |
| 2014 (Kaneko et al., 2014) | Kaneko et al. | 1 | CaCO3, CaOx |
1D PAGE LC-MS/MS |
NA | 53 | Matrix proteins from calcium carbonate stone are mostly associated with cell adhesion and cytoskeleton. These identified proteins may play an important role on urolithiasis in alkaline condition. |
| 2015 (Kaneko et al., 2015) | Kaneko et al. | 16 | COM, COD, HA | 1D PAGE LC-MS/MS |
NA | 65 | Many plasma proteins were frequently detected in stone matrix regardless of the stone components. Identified proteins were involved in inflammation, coagulation process, and osteometabolism. |
| 2016 (Martelli et al., 2016) | Martelli et al. | 4 | Matrix stone | 1D PAGE LC-MS/MS |
NA | 142 | S100A8, S100A9 and neutrophil defensin were identified as the main component of matrix stones. Inflammatory process may be the origin of this kind of rare soft calculi formation but not be the consequence. |
| 2016 (Witzmann et al., 2016) | Witzmann et al. | 2 | CaOx | LC-MS/MS | NA | 1059 | A more complex stone matrix proteome than previously studies was reported. Matrix proteins were related to immune response, inflammation, injury, and tissue repair. |
| 2018 (Kaneko et al., 2018) | Kaneko et al. | 1 | COM, UA | 1D PAGE LC-MS/MS |
NA | 59 | Proteins relevant to cell adhesion, self-defense, and plasma commonly play a major role in the generation of stone. The proteins in the interface likely function to enlarge the stone via the addition of different crystals. |
| 2019 (Wesson et al., 2019) | Wesson et al. | 8 | CaOx | LC-MS/MS | NA | 366 | Osteopontin, mannan-binding lectin serine protease 2, vitamin K-dependent protein Z, prothrombin, and hemoglobin β chain were prominently enriched in matrix, accounting for a mass fraction of >30% of matrix protein. Many identified matrix proteins are reported in intracellular or nuclear locations, indicating a significant role of cell injury in stone formation. |
Notes:
#
Crystals are isolated from the urine of healthy people without urinary stones.
COM, Calcium oxalate monohydrate; COD, Calcium oxalate dihydrate; CaCO3, Calcium carbonate; CaOx, Calcium oxalate; CaP, Calcium phosphate; UA, Uric acid; MAP, Magnesium ammonium phosphate; HA, Hydroxyapatite.