Table 1.
Expression of iron metabolism related proteins and relevance to cancer.
| Protein | Sample type | Relevance in cancer |
|---|---|---|
| Transferrin (Tf) | Serum | High Tf saturation correlated with increased risk of colorectal, lung, and breast cancers and mortality from these cancers (35, 36). |
| Low Tf saturation and high Fe binding capacity correlated with increased risk of stomach cancer (35). | ||
| Melanotransferrin (MTf) | Cell lines | High expression in melanoma and breast cancer lines (37). |
| Tissue samples | Highly expressed in melanoma tissues, but is also detectable in breast, liposarcoma, and lung cancer tissues (37). High expression correlated with high tumor grade and lymph node metastases of colorectal cancer tissues (38). | |
| Serum | High levels detected in colorectal cancer patients (38). | |
| Lactoferrin (Lf) | Cell lines | Low in some prostate lines due to hypermethylation of promoter (39). |
| Tissues | Low/absence of Lf associated with shorter PFS* of breast and prostate cancers (39, 40). Lf lower in gastric cancer samples compared to normal adjacent tissues (41). Lf lower in nasopharyngeal carcinomas than matched normal samples and expression negatively correlated with disease stage (42). | |
| Serum | Patients with prostate cancer had significantly lower levels of Lf compared to healthy controls (39). | |
| Lipocalin 2 (LCN2) | Cell lines | High expression observed in ovarian (43), thyroid (44), breast (45), and colorectal (46) cancer cell lines. |
| Tissue samples | Highly elevated in ovarian, thyroid, colorectal, and liver cancers compared non-tumor tissues (43, 44, 46, 47). Expression positively correlated with breast and thyroid tumor grade (44, 45). | |
| Serum | Higher in ovarian and liver cancer patients compared with healthy controls and predictive of poor OS* for ovarian cancer (43, 46). | |
| Urine | Higher in breast cancer patients than healthy controls (45). | |
| Transferrin receptor 1 (TfR1) | Cell lines | Overexpressed in breast, colon, prostate, leukemia, and esophageal cancer cells (48, 49). |
| Tissue samples | Elevated in esophageal, colon, ovarian and lung tumors vs. normal tissues (48, 49). Expression was elevated with increasing stage of liver cancer and correlated with poor prognosis of gliomas and breast cancers (48). | |
| Serum | Higher in prostate cancer patients than healthy controls (48). | |
| Transferrin receptor 2 (TfR2) | Cell lines | Upregulated in ovarian, colon, and glioblastoma cancer cell lines (50, 51) |
| Tissue samples | Expression correlated with high tumor grade, but inversely correlated with prognosis of glioblastoma (51) and leukemia (52). Expressed in a proportion (~26%) of colon cancers (53). | |
| Divalent metal transporter-1 (DMT1) | Tissue samples | Not detected in normal esophageal tissues, but overexpression of DMT1 was seen in tumors and associated with metastasis (49). |
| Clusters of differentiation 163 (CD163) | Tissue samples | >25% tumor cell positivity correlated with poorer survival of breast cancer patients (54). |
| Clusters of differentiation 91 (CD91) | Tissue samples | Highly expressed in breast, glioma, and endometrial tumors (55). |
| Ferritin (Ft) | Cell lines | Higher in more aggressive types of breast cancer cell lines (56). |
| Tissue samples | FTH1 was overexpressed in esophageal adenocarcinoma (49). FTH1 and FTL highly expressed in HNSCC* tissues compared to normal, associated with metastasis and high FTH1 resulted in shorter PFS (57). FTH1 and FTL higher in glioblastoma samples compared to normal brain, increased with glioma grade and correlated with worse survival (58). Higher FTL in metastatic lesions than primary melanomas (59). FTH1 and FTL were higher in ovarian tumor samples compared to benign and increased with tumor grade (60). High Ft associated with lymph node involvement and survival of breast cancers (61). Ft levels were elevated in colorectal cancers than normal colon mucosa (62). | |
| Serum | Higher in HNSCC patients with metastasis than without (57). Levels elevated compared to normal controls and associated with poor PFS for neuroblastoma (63), Hodgkinson's lymphoma (64), cervical (65), oral squamous cell (66), renal cell (67), T cell lymphoma (68), colorectal (62, 69), breast (70), and ovarian (60) cancers. | |
| Ferroportin | Cell lines | Lower expression in prostate and breast cancer cells (71, 72). |
| Tissue samples | Overexpressed in esophageal adenocarcinoma compared with normal (49). Expression was lower in prostate and breast cancers compared to normal and declined with increasing tumor grade (71–73). Low ferroportin expression levels in pancreatic cancer tissue were significantly associated with poor prognosis (74). | |
| Hepcidin | Tissue samples | High expression observed in prostate and breast cancer tissues compared to normal (71–73). |
| Duodenal cytochrome b (Dcytb) | Tissue samples | Highly expressed in esophageal adenocarcinoma compared with normal (49). High Dcytb expression was associated with increased survival of breast cancer patients (75). |
| Iron regulatory protein-1 (IRP1) | Cell lines | Increased in some prostate and breast cancer cells (76, 77). |
| Tissue samples | Decreased IRP1 expression hepatocellular carcinoma tissues compared to the adjacent non-tumorous liver tissues. Expression of IRP1 was significantly associated with disease stage and vascular invasion and low IRP1 associated with poor OS and PFS (78). | |
| Iron regulatory protein-2 (IRP2) | Cell lines | Consistently increased in prostate and breast cancer cells (76, 77). |
| Tissue samples | IRP2 expression is correlated with histologic grade and molecular subtype of human breast cancer (76). IRP2 was elevated in colorectal cancers compared to normal colon mucosa (79). |
*
OS, Overall survival; PFS, progression-free survival; HNSCC, head and neck squamous cell carcinoma.