Breast Cancer

Protein Biomarkers for Breast Cancer Research

Integrating functional proteomic analysis with genomic risk scores has a significant potential to augment treatment strategies in breast cancer. With IHC4 (ER, PR, HER2, Ki-67) well established, here is a list of very promising protein biomarkers with a potential for clinical adoption.

Tools for analyzing the IHC4:

ER PR HER2 Ki-67

Tools for analyzing upcoming protein biomarkers for breast cancer:

Androgen Receptor (AR) Cytokeratin CD44 Cadherin Caveolin Serpine 1 EGFR Claudin ALDH1 Grb7

AR in human prostate tissue stained with UM800132

Cytokeratin 18 in adenocarcinoma of hu breast stained with UM500045

ESRI in human breast tissue stained with TA503759

Flow cytometric analysis of Ki-67 in Jurkat cells using TA801577

CD44 in adenocarcinoma of hu breast stained with UM500099

Cytokeratin 8 in A549 cells using UM500001

ESR1 in hu adenocarcinoma of breast using TA807239

PR in normal adjacent hu breast tissue stained using UMAB137

Breast cancer is a heterogeneous disease characterized by high genomic instability. Copy number variations, somatic mutations and chromosomal rearrangements are some of the frequently seen genetic alterations. Breast cancer is classified into 4 major subtypes: Luminal A, Luminal B, Triple negative, HER2 enriched ^[1][2]. It is determined by the tumor stage, tumor grade, status of the hormone receptors (PR, ER) and the mutation status of HER2.

Genes in breast cancer:

ATM BRCA1 BRCA2 CDH1 CHEK2 ER HER2 p53 PALB2 PTEN PR STK11 MUC1

Genes that convey moderate risk:

BARD1 BRIP1 CASP8 CTLA4 CYP19A1 FGFR2 H19 LSP1 MAP3K1 MRE11A MSH6 NBN RAD51D TM TERT

MicroRNA in Breast Cancer ^[3]

microRNAs are small non-coding RNA molecules that play a significant role in regulation of gene expression via RNA silencing and post-transcriptional regulation pathways. In breast cancer, differential expression of miRNA plays a critical role in regulating the invasion process by influencing cytoskeletal structure, cell-cell adhesion junctions, cancer cell-ECM interaction, tumor microenvironment, EMT transition and cancer stem cell abilities. Understanding miRNA’s role in breast cancer will enable a better management of breast cancer metastasis.

Human miRNAs in breast cancer:

Up regulated:

hsa-miR-21 hsa-miR-29b hsa-miR-155

Down regulated:

hsa-miR-10b hsa-miR-125 hsa-miR-14

Refer to the table below for a list of all microRNAs involved in breast cancer

Name of miRNA	miRNA expression pattern	Target Genes affected by miRNA	miRNA Role in Invasion-Metastasis Cascade
miR-142-3p	UP	ITGAV, WASL, RAC1, CFL2	Cancer cell invasiveness inhibition
miR-495	UP	JAM-A	Cancer cell migration
miR-10b	UP	HOXD10	Cell migration and invasion
miR-373	UP	ITGA2	Cell migration, metastasis
miR-103/107	UP	DICER1	EMT, cell migration, metastasis
miR-661	UP	NECTIN1, STARD10	EMT, invasion
miR-221/222	UP	TRPS1	EMT, invasion and migration (basal-like BC)
miR-23a	UP	CDH1	EMT, metastasis
miR-374a	UP	WIF1, PTEN, WNT5A	EMT, metastasis
miR-22	UP	TET1-3	EMT, stemness
miR-155	UP	RHOA	EMT, tight junction dissolution, migration and invasion
miR-191/425	UP	DICER1	Invasion and metastasis
miR-221	UP	CDH1	Invasion and metastasis
miR-221	UP	DNMT3B	Pluripotency and stemness
miR-21	UP	TPM1	Tumor growth and malignant phenotype
miR-145	DOWN	JAM-A	Cancer cell motility inhibition
miR-145	DOWN	JAM-A	Cancer cell motility inhibition
miR-198	DOWN	CDCP1	Cell adhesion and migration inhibition
miR-154	DOWN	ADAM9	Cell migration and invasion inhibition
miR-200a	DOWN	CX43	Cell migration and metastasis inhibition
miR-206	DOWN	CX43	Cell migration and metastasis inhibition
miR-181a-5p	DOWN	MMP14	Cell migration inhibition
miR-539	DOWN	LAMA4	Cell migration inhibition (TNBC)
miR-7	DOWN	PAK1	Cell motility and invasiveness inhibition
miR-494	DOWN	PAK1	Clonogenic ability and cell migration, invasion and metastasis inhibition
miR-29b	DOWN	VEGFA, ANGPTL4, PDGF, LOX, MMP9	EMC re-modeling and metastasis inhibition
miR-200c	DOWN	ZEB1, TKS5, MYLK	EMT and invadopodia forming inhibition
miR-153	DOWN	MTDH	EMT and invasion inhibition
miR-124	DOWN	SNAI2	EMT and metastasis inhibition
miR-200b	DOWN	FERMT2	EMT and metastasis inhibition
miR-34	DOWN	SNAI1	EMT inhibition
miR-205	DOWN	ZEB1, ZEB2	EMT inhibition
miR-375	DOWN	SHOX2	EMT inhibition
miR-506	DOWN	SNAI2, VIM, CD151	EMT, adhesion, invasion, and migration inhibition
miR-30a	DOWN	ZEB2	EMT, invasion and distal spreading inhibition (TNBC)
miR-203	DOWN	SNAI1	EMT, invasion and metastasis inhibition
miR-34c	DOWN	NOTCH4	EMT, migration and self-renewal inhibition
miR-320	DOWN	ETS2	Inhibition of tumor micro-environment re-programming
miR-200 cluster	DOWN	WAVE3	Invasion and cell migration inhibition
miR-33a	DOWN	ADAM9	Invasion and metastasis inhibition
miR-193b	DOWN	uPA	Invasion and metastasis inhibition
miR-335	DOWN	TNC, SOX4	Invasion and metastasis inhibition
miR-720	DOWN	TWIST1	Invasion and metastasis inhibition
miR-126	DOWN	ADAM9	Invasion inhibition
miR-181a	DOWN	uPA	Invasion inhibition
miR-193a/b	DOWN	uPA	Invasion inhibition
miR-221/222	DOWN	ITGB4, STAT5A, ADAM17	Invasion inhibition (luminal BC)
miR-224	DOWN	CDC42, CXCR4	Invasion, metastasis inhibition
miR-31	DOWN	WAVE3	Invasive phenotype reduction
miR-126	DOWN	CXCL12	Metastasis inhibition
miR-124a	DOWN		Proliferation and metastasis inhibition
miR-708	DOWN	LSD1	Proliferation, invasion inhibition
miR-30	DOWN	UBC9	Self-renewal
let-7	DOWN	H-RAS, HMGA2	Self-renewal, stemness
miR-590	DOWN	SOX2	Stemness
miR-140	DOWN	SOX2	Stemness, self-renewal
miR-183 cluster	DOWN	BMI1	Stemness, self-renewal

CAR T-cell

Neuroscience

Breast Cancer