AUTHOR=Royse Kathryn E. , Zhi Degui , Conner Michael G. , Clodfelder-Miller Buffie , Srinivasasainagendra Vinodh , Vaughan Laura Kelly , Skibola Christine F. , Crossman David K. , Levy Shawn , Shrestha Sadeep 

TITLE=Differential Gene Expression Landscape of Co-Existing Cervical Pre-Cancer Lesions Using RNA-seq

JOURNAL=Frontiers in Oncology

VOLUME=Volume 4 - 2014

YEAR=2014

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2014.00339

DOI=10.3389/fonc.2014.00339

ISSN=2234-943X

ABSTRACT=Genetic changes occurring in different stages of pre-cancer lesions reflect causal events initiating and promoting the progression to cancer. Coexisting pre-cancerous lesions including low- and high-grade squamous intraepithelial lesion (LGSIL and HGSIL), and adjacent “normal” cervical epithelium from six formalin-fixed paraffin-embedded (FFPE) samples were selected. Tissues from these 18 samples were isolated using laser capture microdissection, RNA was extracted and sequenced. RNA-sequencing (RNA-seq) generated 2.4 billion raw reads in 18 samples, of which approximately 50.1% mapped to known and annotated genes in the human genome. There were 40 genes up-regulated and 3 down-regulated (normal to LGSIL) in at least one third of the sample pairs (same direction and FDR p<0.05) including S100A7 and KLK6. Previous studies have shown that S110A7 and KLK7 are up-regulated in several other cancers, whereas CCL18, CFTR, and SLC6A14, also differentially expressed in 2 samples, are up-regulated specifically in cervical cancer. These differentially expressed genes in normal to LGSIL progression were enriched in pathways related to epithelial cell differentiation, keratinocyte differentiation, peptidase and extracellular activities. In progression from LGSIL to HGSIL, 2 genes were up-regulated and 5 down-regulated in at least 2 samples. Further investigations using coexisting samples, that account for all internal confounders, will provide insights to better understand progression of cervical pre-cancer.