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
AR in human prostate tissue stained with UM800132
Cytokeratin 18 in adenocarcinoma of hu breast stained with UM500045
Cytokeratin 18 in adenocarcinoma of hu breast stained with UM500045
ESRI in human breast tissue stained with TA503759
ESRI in human breast tissue stained with TA503759
Flow cytometric analysis of Ki-67 in Jurkat cells using TA801577
Flow cytometric analysis of Ki-67 in Jurkat cells using TA801577
CD44 in adenocarcinoma of hu breast stained with UM500099
CD44 in adenocarcinoma of hu breast stained with UM500099
Cytokeratin 8 in A549 cells using UM500001
Cytokeratin 8 in A549 cells using UM500001
ESR1 in hu adenocarcinoma of breast using TA807239
ESR1 in hu adenocarcinoma of breast using TA807239
PR in normal adjacent hu breast tissue stained using UMAB137
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

References

  1. Associations between cancer predisposition testing panel genes and breast cancer, Couch et al, JAMA, 2017
  2. Identification of six key miRNAs associated with breast cancer through screening large-scale microarray data, Liang et al, Oncol Lett. 2018
  3. MicroRNAs contribute to breast cancer invasiveness, Fridichova et al., Cell, 2019