Table 1
Prognostic biomarkers for survival in cancer medicine (36)
| Prognostic biomarker | Type of cancer | Clinical significance | Detection | Clinical use |
|---|---|---|---|---|
| Beta-tubulin | NSCLC | High expression of β-tubulin confers worse prognosis | IHC | No |
| BRCA1 | Breast | High expression of BRCA1 confers worse prognosis in untreated patients | IHC | Yes |
| NSCLC | High expression of BRCA1 confers worse prognosis in untreated patients | qRT-PCR | No | |
| CA19-9 | Pancreatic | Higher preoperative CA19-9 levels are associated with lower resectability, more advanced stage and inferior survival I | IHC | No |
| CAIX | RCC | High expression of CAIX is associated with a better prognosis | IHC | No |
| CD44 | Bladder | Expression of CD44 is associated with poor prognosis | qRT-PCR | No |
| CEA | CRC | Elevated preoperative CEA levels in resectable colorectal cancer is associated with poor prognosis | IHC | Yes |
| c-KIT | GIST | GIST patients have a better prognosis if they harbour a mutation in exon 11 of the c-KIT gene | Pathway detection via FDG-PET | Yes |
| ColoPrint | CRC | Prognosis for colorectal cancer patients | Microarray | Yes |
| CTC (e.g. CellSearch) | Melanoma | Increased number of circulating melanoma cells is associated with poor prognosis | Circulating tumour cells | No |
| CRC | Colorectal patients with 3 CTC/7.5 ml of peripheral blood were associated with shorter PFS and OS, i.e. poor prognosis | Circulating tumour cells | Yes | |
| Breast | Breast cancer patients with 5 CTC/7.5 mL of peripheral blood are associated with shorter PFS and OS, i.e. poor prognosis 5 CTC/7.5 ml of peripheral blood is associated with poor prognosis | Circulating tumour cells | Yes | |
| Prostate | Circulating tumour cells | Yes | ||
| Cyclin D1 | Bladder | Expression of Cyclin D1 is associated with low grade, low stage and recurrence | IHC | No |
| Cyclin E | Bladder | Expression of Cyclin E is associated with low stage and survival | IHC | No |
| E-Cadherin | Bladder | E-Cadherin is associated with poor prognosis | IHC | No |
| EGFR | Bladder | Overexpression of EGFR is associated with high grade and high stage | IHC | No |
| NSCLC | High gene copy number of EGFR in NSCLC patients is associated with poor prognosis | FISH / SA | No | |
| EGFR mutation in NSCLC patients is associated with better prognosis in untreated patients | ||||
| Rectal | Overexpression of EGFR in rectal cancers is also associated with poor prognosis | IHC | No | |
| ER | Breast | Patients with ER-positive breast tumours have better survival than patients with hormonal negative tumours | IHC | Yes |
| eXageneBC | Breast | Provides prognosis in node-positive or node-negative breast cancer patients | FISH | Yes |
| Her2/neu | Breast | Patients with Her2/neu-positive breast tumours are more aggressive and have a worse prognosis compared to Her2/neu-negative tumours | FISH | Yes |
| Bladder | Overexpression of Her2/neu is associated with high grade, high stage, poor survival and metastasis in bladder cancer | IHC | No | |
| GIST | Overexpression of Her2/neu in advanced gastric cancer patients is associated with poor prognosis | IHC | No | |
| Her3 | Melanoma | Correlation with increased cell proliferation, tumour progression and reduced survival in melanoma patients | IHC | No |
| ING3 | Melanoma | Reduced nuclear expression associated with poor disease- specific survival in melanoma patients | IHC | No |
| ING4 | Melanoma | Reduced levels of ING4 in melanoma patients is associated with melanoma thickness, ulceration and poor disease-specific survival and overall survival | IHC | No |
| Ki-67 | Bladder | Expression of Ki-67 is associated with progression and recurrence in bladder cancer | IHC | No |
| Breast | Expression of Ki-67 is associated with proliferation and progression in breast cancer | IHC | No | |
| K-ras | NSCLC | K-ras mutation is associated with poor prognosis in NSCLC patients | SA | Yes |
| LOH at 18q | CRC | Associated with metastasis and poor prognosis in colorectal tumours | PCR | No |
| MammaPrint | Breast | A 70-gene prognostic assay used to identify breast cancer cases at the extreme end of the spectrum of disease outcome by identifying patients with good or very poor prognosis | Microarray | Yes |
| Mammostrat | Breast | This standard purely prognostic test uses five antibodies with manual slide scoring to divide cases of ER-positive, lymph node negative breast cancer tumours treated with tamoxifen alone into low-, moderate- or high-risk groups | IHC | Yes |
| MMP-2 | Bladder | Expression of MMP-2 is associated with poor prognosis in bladder cancer patients | PCR | No |
| MSI status | CRC | High frequency MSI colorectal tumours are associated with better prognosis and show improved relapse-free survival | IHC | No |
| NCOA3 | Melanoma | Increased levels in melanoma patients correspond to poor relapse-free survival and disease-free survival | IHC | No |
| Oncotype DX | Breast | A 21-gene multiplex test used for prognosis to determine 10- year disease recurrence for ER-positive, lymph node negative breast cancers using a continuous variable algorithm and assigning a tripartite recurrence score | qRT-PCR | Yes |
| p21 | Bladder | Overexpression of p21 is associated with poor prognosis | IHC | No |
| p53 | Bladder | Overexpression of p53 is associated with poor prognosis | IHC | No |
| NSCLC | High expression of p53 in NSCLC patients confers worse prognosis in untreated patients | IHC | No | |
| NSCLC | p53 mutation in NSCLC patients is associated with worse prognosis | SA | No | |
| PR | Breast | Patients with PR-positive breast tumours have better survival than patients with hormonal-negative tumours | IHC | Yes |
| Rb | Bladder | Overexpression of Rb is associated with poor prognosis | IHC | No |
| RRMI | NSCLC | High expression of RRMI in NSCLC patients confers better prognosis in untreated patients | AQUA | No |
| VEGF | RCC | Overexpression of VEGF is associated with poor prognosis in clear cell renal carcinoma patients | IHC | Yes |
[i] AQUA – automated quantitative analysis; CA19-9 – carbohydrate antigen 19-9; CAIX – carbonic anhydrase IX; CEA – carcinoembryonic antigen; CRC – colorectal tumour; CTC – circulating tumour cells; EGFR – epidermal growth factor receptor; ER – oestrogen receptor; FDG – 18F-fluorodeoxyglucose; FISH – fluorescent in situ hybridisation; GIST – gastrointestinal stromal tumour; IHC – immunohistochemistry; LOH – loss of heterozygosity; MMP-2 – matrix metalloproteinase-2; MSI – microsatellite instability; NSCLC – non-small cell lung cancer; OS – overall survival; PET – Positron emission tomography; PFS – progression-free survival; PR – progesterone receptor; qRT-PCR – quantitative real time polymerase chain reaction; Rb b – retinoblastoma; RCC – renal cell carcinoma; RRMI – ribonucleotide reductase messenger 1; SA – sequence analysis; VEGF – vascular endothelial growth factor
Table 2
Predictive biomarkers for treatment selection in cancer medicine (36)
| Predictive biomarker | Type of cancer | Clinical significance | Detection | Clinical use |
|---|---|---|---|---|
| BRCA1 | NSCLC | High expression of BRCA1 in NSCLC patients predicts resistance to cisplatin-based chemotherapy | qRT-PCR | No |
| Breast | High expression of BRCA1 in breast cancer can predict response to chemotherapy | IHC | Yes | |
| CAIX | RCC | Expression of CAIX in renal cell carcinoma is predictive of sensitivity of treatment with interleukin-2 therapy | IHC | No |
| c-KIT | GIST | GIST patients carrying the mutation on exon 11 of the c-KIT gene benefit from imatinib and sunitinib treatment, however most patients develop resistance to these over time | SA | Yes |
| EGFR1 | NSCLC | EGFR1 mutations in patients with NSCLC are predictive for response to either gefitinib or erlotinib treatment | IHC | Yes |
| CRC | EGFR1 gene amplification appears to be a predictive factor for response to anti-EGFR1 antibody treatment in CRC | PCR | Yes | |
| ER | Breast | High cellular expression of ER predicts benefit from tamoxifen- based chemotherapy | IHC | Yes |
| ERCC1 | NSCLC | High expression of ERCC1 in NSCLC patients predicts resistance to cisplatin-based chemotherapy | IHC | No |
| Her2/neu | Breast | Breast cancer patients with Her2/neu overexpressing tumors benefit from treatment with trastuzumab in the metastatic as well as in the adjuvant setting | FISH | Yes |
| Gastric | Expression of Her-2/Neu in gastric cancer is predictive of patient sensitivity towards treatment with 5-FU, doxorubicin, trastuzumab and platinum-based chemotherapy | FISH | No | |
| K-ras | NSCLC | K-ras mutation positivity in NSCLC patients predicts lack of benefit from adjuvant chemotherapy in early disease and resistance to treatment with EGFR TKI in advanced disease | SA | Yes |
| CRC | K-ras mutation positivity in stage IV CRC patients predicts considerably less benefit from EGFR-specific antibody like cetuximab and panitumumab | PCR | Yes | |
| LOH at 18q | CRC | Useful in identifying patients with resected stage III colon cancer most likely to benefit from 5-FU based adjuvant chemotherapy | PCR | No |
| MGMT | Glioblastoma | Methylation of MGMT promoter is predictive of sensitivity of glioblastoma to temozolomide | PCR | No |
| NuvoSelect | Breast | A combination of several pharmacogenomic genesets used primarily to guide selection of therapy in breast cancer patients. This test also provides the ER and HER2 mRNA status | Microarray | Yes |
| p53 | NSCLC | High p53 expression in NSCLC patients predicts sensitivity to cisplatin-based chemotherapy, however p53 mutation is predictive of resistance to cisplatin-based chemotherapy | IHC/SA | No |
| PR | Breast | High cellular expression of PR predicts benefit from tamoxifen- based chemotherapy | IHC | Yes |
| Roche AmpliChip | Breast | Low expression of CYP2D6 predicts resistance to tamoxifen- based chemotherapy in breast cancer patients | Microarray | Yes |
| Rotterdam Signature | Breast | A 76-gene assay used to predict recurrence in ER-positive breast cancer patients treated with tamoxifen | Microarray | Yes |
| RRMI | NSCLC | High expression of RRM1 in NSCLC patients predict resistance to cisplatin-based chemotherapy | qRT-PCR | No |
| TP | GIST | Predictive of sensitivity of treatment to 5-FU- and capcetabine- based chemotherapy in gastric cancer patients | IHC/PCR | No |
| CRC | Expression of TP in metastatic colorectal patients is predictive of sensitivity of treatment to 5-FU and capcetabine based chemotherapy | IHC/qRT-PCR | No | |
| PTEN | Breast | PTEN mutation can result in reduced sensitivity of treatment with trastuzumab in breast cancer patients | IHC | No |
[i] CAIX – carbonic anhydrase IX; CRC – colorectal tumour; EGFR – epidermal growth factor receptor; ER – oestrogen receptor; ERCC1 – excision repair cross-complementation group 1; FISH – fluorescent in situ hybridisation; GIST – gastrointestinal stromal tumour; IHC – immunohistochemistry; LOH – loss of heterozygosity; MGMT – O6-methylguanine-DNA methyltransferase; NSCLC – non-small cell lung cancer; PCR – polymerase chain reaction; PR – progesterone receptor; RRMI – ribonucleotide reductase messenger 1; qRT-PCR – quantitative real-time polymerase chain reaction; RCC – renal cell carcinoma; SA – sequence analysis; TK1 – tyrosine kinase inhibitor; TP – thymidine phosphorylase