Clustering of RNA co-expression network identifies novel long non-coding RNA biomarkers in squamous cell carcinoma

Abstract

Long non-coding RNAs (lncRNAs) have been shown to play an important role in cancer progression. Cutaneous squamous cell carcinoma is the most common metastatic skin cancer with increasing incidence worldwide. The prognosis of the metastatic cSCC is poor, and currently there are no established biomarkers to predict metastatic risk nor specific therapeutic targets for advanced or metastatic cSCC. To elucidate the role of lncRNAs in cSCC, RNA sequencing of patient derived cSCC cell lines and normal human epidermal keratinocytes was performed. The correlation analysis of differentially expressed lncRNA and protein-coding genes revealed six distinct clusters. One of the upregulated clusters involved genes related to cell motility. Upregulation of the expression of lncRNAs involved in cSCC cell motility in cSCC and head and neck SCC (HNSCC) cells was confirmed by qRT-PCR. Upregulation of HOTTIP and LINC00543 was also noted in SCC tumors in vivo and was associated with worse prognosis in HNSCC and lung SCC cohorts in the TCGA data, respectively. Altogether, these results reveal a novel set of lncRNAs involved in cSCC cell locomotion. These lncRNAs may serve as potential novel biomarkers or a biomarker panel and as putative therapeutic targets in locally advanced and metastatic cSCC.