High Expression of Three-Gene Signature Improves Prediction of Relapse-Free Survival in Estrogen Receptor-Positive and Node-Positive Breast Tumors
BIOMARKER INSIGHTS
Authors: Thakkar, Arvind; Raj, Hemanth; Ravishankar; Muthuvelan, Bhaskaran; Balakrishnan, Arun; Padigaru, Muralidhara
Abstract
The objective of the present study was to validate prognostic gene signature for estrogen receptor alpha-positive (ER alpha+) and lymph node (+) breast cancer for improved selection of patients for adjuvant therapy. In our previous study, we identified a group of seven genes (GATA3, NTN4, SLC7A8, ENPP1, MLPH, LAMB2, and PLAT) that show elevated messenger RNA (mRNA) expression levels in ER alpha (+) breast cancer patient samples. The prognostic values of these genes were evaluated using gene expression data from three public data sets of breast cancer patients (n=395). Analysis of ER alpha (+) breast cancer cohort (n=195) showed high expression of GATA3, NTN4, and MLPH genes significantly associated with longer relapse-free survival (RFS). Next cohort of ER alpha (+) and node (+) samples (n=109) revealed high mRNA expression of GATA3, SLC7A8, and MLPH significantly associated with longer RFS. Multivariate analysis of combined three-gene signature for ER alpha (+) cohort, and ER alpha (+) and node (+) cohorts showed better hazard ratio than individual genes. The validated three-gene signature sets for ER alpha (+) cohort, and ER alpha (+) and node (+) cohort may have potential clinical utility since they demonstrated predictive and prognostic ability in three independent public data sets.
Characterization of the human laminin beta 2 chain locus (LAMB2): linkage to a gene containing a nonprocessed, transcribed LAMB2-like pseudogene (LAMB2L) and to the gene encoding glutaminyl tRNA synthetase (QARS)
CYTOGENETICS AND CELL GENETICS
Authors: Durkin, ME; Jager, AC; Khurana, TS; Nielsen, FC; Albrechtsen, R; Wewer, UM
Abstract
The laminin beta 2 chain is an important constituent of certain kidney and muscle basement membranes. We have generated a detailed physical map of a 110-kb genomic DNA segment surrounding the human laminin beta 2 chain gene (LAMB2) on chromosome 3p21.3 --> p21.2, a region paralogous with the chromosome 7q22 --> q31 region that contains the laminin beta 1 chain gene locus (LAMB1). Several CpG islands and a novel polymorphic microsatellite marker (D3S4594) were identified. The 3' end of LAMB2 lies 16 kb from the 5' end of the glutaminyl tRNA synthetase gene (QARS), About 20 kb upstream of LAMB2 we found a gene encoding a transcribed, non-processed LAMB2-like pseudogene (LAMB2L). The sequence of 1.75 kb of genomic DNA at the 3' end of LAMB2L was similar to exons 8-12 of the laminin beta 2 chain gene. The LAMB2L-LAMB2-QARS cluster lies telomeric to the gene encoding the laminin-binding protein dystroglycan (DAG1).