Digging into novel biomarkers of squamous cell carcinoma in Koreans using transcriptome profiling of exosomal RNA

With the advent of breakthrough next-generation sequencing (NGS), quite a few novel mutations have been identified for cutaneous squamous cell carcinoma (SCC). While not all of these aberrations may be significant from clinical perspective, promising outcome have been obtained in a number of early phase studies that evaluated the efficacy of new molecular inhibitors against these potential targets. However, since SCC is a cancer with one of the highest mutation rates across all field of oncology, efforts to nail down the “driver” mutation have largely been futile. One of cancer research areas that has gained impetus from recent advances in NGS technology concerns liquid biopsy and exosomes. Exosomes, secretory bodies released from cancers cells to neighboring cells to deliver various chemical signals, contain RNA, proteins, lipids and metabolites. Exosomal content is reflective of the cell type of origin. In cancer cells, the regulatory circuit which guards exosome homeostasis is co-opted to promote cancer cell survival and metastasis. Also, in the case of cutaneous melanoma, the content of tumor-derived vesicles, especially circulating tumor DNA (ctDNA), long noncoding RNA (lncRNA), and micro RNA (miRNA) were shown to enter lymphatic circulation and interact with B cells in the lymph node, thereby exerting a profound influence on tumor microenvironment and immunology. As cancer exosomes contain numerous proteins, RNA and lipids, exosomal sequencing (ExoSeq) represents an excellent source of large-scale bioinformatic analysis, particularly transcriptomes. Up to this point, the theoretical usefulness of ExoSeq in cutaneous SCC has not yet adequately backed up with substantial evidence. In the current presentation, the author discusses interim results of combined exosomal-whole exome sequencing using surgical specimens of high-grade SCC in Korean patients.