Table 1.
Evaluation methods for emerging biomarkers.
| Evaluation Groups | Parameters | Indicators | Detection | Method | References |
|---|---|---|---|---|---|
| TME | Inflammatory infiltrated cells | TAM | CD68, CD163 | IHC | [79] |
| TAN | CD15, CD32, CD35 | [80] | |||
| T helper | CD4 | [81] | |||
| Cytotoxic T cells | CD8 | [82] | |||
| Memory T cells | CD8, CD4, CTLA-4 | [83] | |||
| Tregs | FOXP3, CD4, CD25 | [84] | |||
| DC | CD141, CLEC9, CD11c | [85,86] | |||
| NK | CD16, CD56, PD-L1, PD-L2 | [87] | |||
| B lymphocytes | CD20 | [88] | |||
| Stromal cells | CAF | αSAM, CD10, FSP1, AEBP1 | [89,90] | ||
| Schwann cells | S100, GFAP, p75NTR | [91] | |||
| MSC | SC | Sox2, Oct4, CD133, Nestin, c-kit | [92] | ||
| Fibers | Collagen type I | T. Masson, van Gieson | HC | [93,94] | |
| Collagen type III | [94] | ||||
| Elastic fibers | Orcein, Gomori, Snook, Wilder, Verhoeff | [94] | |||
| Interstitial fluid | Proteoglycans | Alcian blue | [95] | ||
| Fibronectin | Antifibronectin | IHC | [96] | ||
| Laminin | Antilaminin | [97] | |||
| Vitronectin | Antivitronectin | [98] | |||
| Growth factor | TGF-β | AS | [99] | ||
| Cytokines | Lymphokines | ELISA | [100] | ||
| Proteases | Metalloproteinases | [100] | |||
| Oxygen (ROS) | GSH/GSSG | [100] | |||
| 3D structure | Fibres and Cellular elements | Topology | Graph theory | [101,102] | |
| Mechanical forces | Focal adhesions | (F-actin, myosin II, α-actin, fascin) | IF | [103] | |
| Stress fibres | [103] | ||||
| Mechanotransduction | Mechano-actuated shuttling proteins | (β-catenin, zyxin) | [103] | ||
| LINC complex | (SUN and nesprins) | [103] | |||
| Systemic factors | Glycolic index | ↑metabolic index | 18FDG | PET | [104] |
| pH | Acidosis | Electrolytes serum concentration | Enzymatic | [105] | |
| Oxygen saturation | Hypoxia | ↑HIF-1, ↑lactate | IHC | [106] | |
| Metabolism | Inflammatory response | ↓VEGF | AS, ELISA | [107] | |
| Intestinal microbiota | Dysbiosis | ↑Bacteroids | MALDI-TOF MS | [76,108,109,110] | |
| ↑Fusobacterium | NGS | [76,108,109,110] | |||
| ↑Porphyromonas | 16S rRNA | [76,108,109,110] | |||
| ↑Enterobacter | [76,108,109,110] | ||||
| ↑Cybrobacter | [76,108,109,110] | ||||
| Nervous system | Deregulation | ↑Norepinephrine, | HPLC | [62] | |
| ↑Dopamine | [111] | ||||
| ↑substance P | [112] | ||||
| ↓β-endorphins | [113] |
AS: absorption spectrometry; DC: dendritic cells; CAF: cancer-associated fibroblasts; 18FDG: fluorodeoxyglucose; GSH: glutathione; GSSG: glutathione disulfide; HC: histochemistry; HPLC: high-performance liquid chromatography; IF: immunofluorescence; IHC: immunohistochemistry; LINC: linker of nucleoskeleton and cytoskeleton; MALDI-TOF MS: matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; MSC: mesenchymal stem cells; NGS: next-generation sequencing; NK: natural killer cells; PET: positron emission tomography; ROS: reactive oxygen species; 16S rRNA: ribosomal RNA 16S; SC: stem cells; TAM: tumor-associated macrophage; TAN: tumor-associated neutrophils; TME: tumor microenvironment; Tregs: regulatory T cells. Adapted from Noguera et at., 2019 [46].