Table 2.
A compilation of some of the most relevant studies that made use of in vitro, xenografts, or samples from non-human models for the search of molecular biomarkers relevant to the diagnosis, prognosis, and/or therapeutical strategies in cancer research.
| Reference | Type of cancer | Methodology |
Sample | Species | Statistically validated targets |
Type of biomarker | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Prefractioning/enrichment | Target selection | Number of targets | Mass spectrometry (MS) approach | Protein ID | Number of proteins | |||||
| (107) | Breast | IMAC (phospho) | SILAC shotgun proteomics | 100 | Parallel reaction monitoring (PRM) | MCF7, PC3, HL60 cells | H. sapiens | MAPK, PI3K/mTOR, and CDK | – | Therapeutic |
| (108) | Breast | – | Label-free (LF) shotgun proteomics | 258 | LF-SRM | MCF10A cells | H. sapiens | CDH1; CDH2; vimentin | Therapeutic | |
| (109) | Breast | Phosphatase treatment | Literature | 4 | Labeled reference peptide (LRP)-SRM | MCF-7 cells | H. sapiens | ER, HER2, RAF, and ERK1 | 4 | Prognostic |
| (110) | Breast | SCX | Literature | 76 | Stable isotope dilution-selected reaction monitoring (SID-SRM) | MCF-7 cells | H. sapiens | SLC2A1, HSPA5, LDHA, PGR, and TFF1 | 12 | Prognostic |
| (111) | Breast | – | SILAC shotgun proteomics | 8 | LF-PRM | 231-BR; MDA-MB-231 cells | H. sapiens | MMP1; EFNB1; STOM1; UAP1; MYCT1; TGM2; S100A4; LCP1 | 8 | Prognostic |
| (112) | Breast | Avidin-agarose | Isotope-coded ATP-affinity shotgun proteomics | 120 | SID-SRM; isotope-coded ATP-affinity | MCF-7 cells | H. sapiens | CHK1, CDK1, and CDK2 | 120 | Therapeutic |
| (113) | Breast | Immunoenrichment; SDS-PAGE | Literature | 1 | SWATH and MS1 filtering | SK-BR3 cells | H. sapiens | ErbB2 | 1 | Diagnostic |
| (114) | Breast | Immunoprecipitation of decorin and periostin | Isobaric tags for relative and absolute quantitation (iTRAQ) shotgun proteomics | 2 | SID-SRM | MDA-MB-231; T47D; BT-20 cells | H. sapiens | Decorin; periostin | 2 | Therapeutic |
| (26) | Breast | 2D-LC | LF shotgun proteomics | 319 | SID-SRM | 30 cell lines | H. sapiens | CLTC, DPYSL2; ABAT; many others | Diagnostic; Prognostic | |
| (115) | Breast | 2D-gel | 2D-DIGE | 11 | LF-SRM | ZR-75-1, MDA-MB-231, and MCF-10A cells | H. sapiens | HSP105, KRT8, KRT18, RPLP0, and RAD23B | 5 | Therapeutic |
| (116) | Breast | 2D-LC | iTRAQ shotgun proteomics | 12 | SID-SRM | MCF7 cells | H. sapiens | HSPA8, LDHA, NACA, CTSD, PKM2, IGF-1R | 6 | Therapeutic |
| (29) | Breast | – | Transcriptomics database; LF shotgun proteomics; | 20 | SID-SRM | SK-BR-3 and MDA-MB-231 cells | H. sapiens | KPNA2; CDK1 | 2 | Prognostic |
| (117) | Breast | Cell nuclei enrichment | Literature | 2 | LF-SRM | MCF-7 cells | H. sapiens | NF-κB2; Stat1 | 2 | Prognostic |
| (118) | Breast | – | LF shotgun proteomics | 60 | LF-SRM | Tissue | Mus musculus | Osteopontin and fibulin-2 | 2 | Diagnostic; Prognostic |
| (119) | Colon | Lectin affinity | Literature | 2 | LRP-SRM | WiDr cells | H. sapiens | TIMP1; PTPK | 2 | Diagnostic |
| (42) | Colon | Laser microdissection; SDS-PAGE | Literature | 22 | SID-SRM | HCT116, HT29, KM12, SW620, KM12C, KM12L4A, and KM12SM cells | H. sapiens | B-catenin; c-Src; c-Myc; PP2A | 4 | Prognostic |
| (120) | Colon | Affinity depletion of 3 abundant proteins; SCX | SILAC shotgun proteomics | 9 | SID-SRM | Serum | M. musculus | MGAM; COL1A1; ITIH3 and F5 | 4 | Diagnostic |
| (121) | Colon | affinity depletion of 3 abundant proteins; SCX | SILAC shotgun proteomics | 20 | SID-SRM | Serum | M. musculus | Cysttin C, secreted phosphoprotein 1, pyruvate kinase 3, procollagen C-proteinase enhancer, nucleobindin, HSP1A, nucleolin, fibronectin, profilin, HSP8 | 10 | Diagnostic |
| (122) | Colon; lung; melanoma; leukemia; myeloma | SDS-PAGE | Literature | 221 | SID-SRM | Multiple cell lines (>25) | H. sapiens | 95 | Therapeutic | |
| (123) | Glioblastoma | Secretome enrichment | Shotgun | 65 | SID-SRM | U87 cells | H. sapiens | EGFR, EGFRvIII, and/or PTEN | 62 | Therapeutic |
| (124) | Kidney | Immunoaffinity | Literature | 1 | SID-SRM | PRC3 cells | H. sapiens | CA12 | 1 | Diagnostic |
| (125) | Kidney; Breast | – | Shotgun | 114 | LRP-PRM | BT474 and Sum159 xenograft | H. sapiens | HER2 | 104 | Diagnostic |
| (126) | Leukemia | IMAC (phospho) | LF shotgun proteomics | 25 | LF-SRM | AML-193, CMK, CTS, HEL, Kasumi-1, KG-1, MV4-11, and P31/FUJ cells | H. sapiens | PI3K, MEK, and JAK | 3 | Therapeutic |
| (127) | Lung | SDS-PAGE | Literature | 1 | LF-SRM | A431 cells | H. sapiens | 6 phosphosites in EGFR | 1 | Therapeutic |
| (63) | Lung | Enrichment for desthiobiotinylated and tyrosine-phosphorylated peptides | LF shotgun proteomics | 264 | LRP-SRM | HCC366 and H2286 cells | H. sapiens | Kinases | Therapeutic | |
| (64) | Lung | Microdissection | Literature | 1 | SID-SRM | Xenograft cell culture | M. musculus | EGFR | 1 | Therapeutic |
| (128) | Lung; skin; colon | Phosphotyrosine immunoenrichment | Literature | 83 | LRP-PRM | A431; SW480 and 11–18 cells | H. sapiens | EGFR; FLK2; EPHA1; FAK1; FGFR2; IGF1R; LYN; PGFRA; PTK7; SRC; VGFR2; and YES | 21–28 | Therapeutic |
| (129) | Multiple myeloma | SDS-PAGE | Literature | 15 | SID-SRM | RPMI-8226; U266 cells | H. sapiens | NF-κB1 and 2, RelB/p50, Bcl-2, Mcl-1, Bfl-1, Bcl-xL, Bid, Bim, FANCD2, FANCI | – | Therapeutic |
| (130) | Ovary | Affinity depletion of 20 abundant proteins; IEF; SDS-PAGE | LF shotgun proteomics | 14 | LF-SRM | Xenograft mouse models | M. musculus | AGRN, PSME2, TPI1, DDAH2, GM2A, YWHAB, YWHAH, PSMA, PSMB1–4 | Diagnostic | |
| (131) | Ovary | – | Literature | 1 | Ion-trap LRP-pSRM | 2008 cell line | H. sapiens | SOD1 | 1 | Therapeutic |
| (132) | Ovary | Immunoprecipitation; SDS-PAGE | Shotgun | 2 | SID-SRM | OVTOKO, OVISE, MCAS, OVKATE, OVSAHO, OVMANA, OVSAYO, OVCAR-3, RMG-I, and RMG-II cells | H. sapiens | Brg1; ARID1A | 2 | Diagnostic |
| (84) | Pancreas | SDS-PAGE | Literature | 1 | SID-SRM | DLD1; COLO-205; SW480; A549; HCT116; HT-29 cells | H. sapiens | KRAS | 1 | Diagnostic |
| (89) | Pancreas | Membrane and cytosolic fractions—centrifugation | Literature | 25 | SID-SRM | PK9, CFPac-1, PK1, SUIT2, AsPC1 human cells | H. sapiens | dCK; UMP-CMP; cN-III; ENT1 | 4 | Therapeutic |
| (133) | Prostate | – | Literature | 1 | SID-SRM | VCaP and LNCaP cells | H. sapiens | ERG3 | 1 | Diagnostic; prognostic |
A variety of different targeted proteomic methods were employed and are also described.