Orphan Non-coding RNAs in Detecting and Targeting Head and Neck Cancers

Introduction: There is an unmet need for more reliable and accurate tools to help better guide diagnosis for Head and Neck Cancers. Orphan non-coding RNAs (oncRNAs) are a class of small non-coding RNAs that are only observed in cancer and diseased tissues, and not in normal cells. Hence, they can serve as molecular fingerprints to communicate underlying disease biology and are detectable in both blood and solid tissues.

Methods: We discovered a class of small non-coding RNAs (30-80 nucleotide long) that were found in cancer tissues but not in normal tissue adjacent to the tumor, termed orphan non-coding RNAs (oncRNAs). Of these, there were 83,173 annotated oncRNAs with expression pattern distinctive to HNSCC compared to healthy cells or other cancer types. Furthermore, some subsets of oncRNAs can used to further stratify HNSCC by their original sites of origin.

Results: Small RNA-sequencing performed on matched tumor-blood samples of Mass Eye and Ear patients with primarily advanced-stage OCSCC (Cohort 1) revealed that oncRNAs can be detected in blood and, importantly, oncRNAs that were previously identified as highly enriched in tumor samples were also enriched in blood samples, suggesting that oncRNAs could be potentially used as a biomarker. Remarkably, the same oncRNAs are not observed in plasma samples from healthy controls, or patients with a different primary cancer type of the head and neck. Of these oral cavity oncRNAs, oncRNA64585 (genomic location—chr8: 83809169-83809205) emerged as a very promising target as it is highly enriched in both solid and plasma samples. Furthermore, higher expression of oncRNA64585 was associated with more advanced disease (p = 1.17 e-23) as well as worse prognosis (p =0.0085)

Conclusions: OncRNAs are a group of small non-coding RNA that are highly enriched in cancer cells but largely absent in normal cells. OncRNAs can be used as “barcodes” to stratify Head and Neck Cancers by their original tumor sites. OncRNAs can be detected in blood samples of patients with oral cavity SCC that matched their solid tumor profile. Levels of a certain oncRNA correlate with disease progression and prognosis.