Cyclooxygenase-2 as a biomarker with diagnostic, therapeutic, prognostic, and predictive relevance in small animal oncology

Szweda, Marta; Rychlik, Andrzej; Babińska, Izabella; Pomianowski, Andrzej

doi:10.2478/jvetres-2020-0018

Figures & Tables

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

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

Cyclooxygenase-2 as a biomarker with diagnostic, therapeutic, prognostic, and predictive relevance in small animal oncology

Figures & Tables

Predictive biomarkers for treatment selection in cancer medicine (36)

Prognostic biomarkers for survival in cancer medicine (36)

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