Table 1.
Detailed information for the top 10 candidate proteins found to be DA in TIF samples obtained from luminal, Her2, and TNBC BC subtypes. Parentheses around arrows denote a protein was borderline significant (i.e., corrected P‐value < 0.05, and log‐fold change close to, but not quite reaching, the cutoff of −|+ 1) (a) Primary UniProt nomenclature, (b) Primary SwissProt nomenclature, (c) see Table S6 for details, (d) Arrows denote abundance directionality (up or down) in TIF samples, (e) see Table S7 and Fig. 7 for details, (f) see Fig. 7 for details, (g) see Fig. 7 for details, (h) see Table S8 for details, (↓)—borderline significant. Additional references in table are [104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146].
| Gene symbol (a) | Protein name (b) | Molecular function/Biological process | Differential abundancy in TIF (c) | Differential expression in tumor biopsy (e) | Correlation TIF/Tumor (f) | Expression in normal breast tissue (close vicinity) (g) | Far‐distant | Presence in pooled NIF/FIF | Presence in exosome database [40] | Presence in Plasma database [39, 118] | Secreted (BC cell lines) [42] | Presence in serum (PubMed) | Expression in 33 normal human tissues (h) | Expression in BC biopsies (PubMed) | Expression in other cancers (i) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Luminal | Her2 | TNBC | Luminal | Her2 | TNBC | ||||||||||||||
| AGR3 | Anterior gradient protein 3 | Dystroglycan binding; negative regulation of cell death | ↑ (d) | Not significant | ↓ | High (3+) | Medium/Low | Low (1+ – 0) | Yes | Low/Neg | Low/Neg | No | Yes | Yes | Yes | Yes [88] | Neg but medium in bladder, stomach, small intestine, colon and rectum | mRNA [139]; protein [88, 89, 109, 146] | Liver (protein [119, 129]), ovarian (mRNA [144]; protein [141]), prostate (mRNA [122]) |
| BCAM | Lutheran/basal cell‐adhesion molecule, Lu/Bcam/CD239 | Transmembrane signaling; cell adhesion and migration | ↑ | ↓ | ↓ | High (3+) | Medium/Low | Low (1+ – 0) | Yes | Low/Neg | Low/Neg | No | Yes | Yes | Yes | Yes [90] | Neg but medium in bladder, fallopian tube, esophagus, heart, kidney, lung, parathyroid, prostate and thyroid | Protein [90, 91] | Colon (protein [134]), hepatocellular carcinoma (plasma [130]; protein [113]), ovarian (protein [110]), pancreatic cancer (serum [115]), skin (protein [104, 106]) |
| CELSR1 | Cadherin EGF LAG seven‐pass G‐type receptor 1 | Transmembrane signaling; cell adhesion and migration | ↑ | (↓) | ↓ | High (3+) | Low (1+ – 0) | Low (1+ – 0) | Yes | Low/Neg | Low/Neg | No | No | No | Yes | No Data | Neg in all | Gene copy [99, 121] | Hepatocellular carcinoma (DNA methylation [120]), glioma (mRNA [142]), lymphocytic leukemia (protein [127]) |
| MIEN1 | membrane‐anchored protein C35, C17orf37 | Regulation of cell migration and apoptosis | ↓ | ↑ | ↓ | Medium (2+) | High (3+) | Low (1+ – 0) | Yes | Low/Neg | Low/Neg | No | Yes | Yes | Yes | No Data | Neg in all | Protein [76, 93, 94, 111] | Ovarian (mRNA [128]), oral (mRNA & protein [132]) |
| NAT1 | N‐acetyltransferase 1 | Drugs and carcinogens metabolizing enzyme | ↑ | Not significant | ↓ | High (3+) | Low (1+ – 0) | Low (1+‐ 0) | Yes | Low/Neg | Low/Neg | No | Yes | No | No | No Data | Neg in all but medium in bladder | mRNA [25, 105, 107, 108]; protein [92, 112, 126] | No data |
| PIP4K2B | PhosphatidyliNositol‐5‐phosphate (PtdIns5P)‐4‐kinase | Stress‐regulated lipid kinase; cell surface receptor signaling pathway | Not significant | ↑ | ↓ | Medium (2+) | High (3+) | Low (1+ – 0) | Yes | Comparable | Comparable | No | Yes | Yes | No | No Data | Neg or very low in all | mRNA & protein [85, 125] | Lung adenocarcinoma (mRNA [138]), myeloid leukemia (mRNA [145]) |
| SEC23B | Sec23 Homolog A | GTPase activator activity; cellular transport | Not significant | ↑ | ↓ | Medium (2+) | High (3+) | Low (1+ – 0) | Yes | Low/Neg | Low/Neg | No | Yes | No | Yes | No Data | Neg in all but medium in eye | mRNA & protein [133] | Thyroid & endometrial (protein [133]) |
| THTPA | Thiamine triphosphatase | Hydrolase activity; metabolic and energy processes | ↑ | Not significant | ↓ | High (3+) | Low (1+ – 0) | Low (1+ – 0) | Yes | Low/Neg | Low/Neg | No | No | No | No | No Data | Neg or very low in all | No data | No data |
| TMEM51 | Transmembrane protein | Unknown function | ↑ | ↓ | ↑ | Medium (2+) | Low (1+ – 0) | High (3+) | Yes | Low | Low | No | Yes | No | No | No Data | Neg in all but medium in bladder, kidney and pancreas | No data | Pancreatic (mRNA [136]) |
| ULBP2 | UL16‐binding protein 2 | Cell surface glycoprotein; natural killer cell activation; immune response | ↓ | Not significant | ↑ | Low (1+ – 0) | Low (1+ – 0) | High (3+) | Yes | Low/Neg | Low/Neg | No | No | No | Yes | Yes [124, 131] | Neg in all but medium in heart | mRNA [143]; protein [96] | Colon (mRNA [140]), lung (plasma [123]), ovarian (mRNA [116]; protein [114], pancreatic (protein [135, 137]; plasma [117]) |