Unique somatic and malignant expression patterns implicate PIWI-interacting RNAs in cancer-type specific biology

Abstract

Human PIWI-interacting RNAs (piRNAs) are known to be expressed in germline cells, functionally silencing LINEs and SINEs. Their expression patterns in somatic tissues are largely uncharted. We analyzed 6,260 human piRNA transcriptomes derived from non-malignant and tumour tissues from 11 organs. We discovered that only 273 of the 20,831 known piRNAs are expressed in somatic non-malignant tissues. However, expression patterns of these piRNAs were able to distinguish tissue-of-origin. A total of 522 piRNAs are expressed in corresponding tumour tissues, largely distinguishing tumour from non-malignant tissues in a cancer-type specific manner. Most expressed piRNAs mapped to known transcripts, contrary to “piRNA clusters” reported in germline cells. We showed that piRNA expression can delineate clinical features, such as histological subgroups, disease stages, and survival. PiRNAs common to many cancer types might represent a core gene-set that facilitates cancer growth, while piRNAs unique to individual cancer types likely contribute to cancer-specific biology.

PIWI Proteins and PIWI-Interacting RNA: Emerging Roles in Cancer

“…In cancer tissues, aberrant expression of piRNAs implied by global hypomethylation and focal hypermethylation are probably potential cancer-specific signatures [72, 73]. Accumulating evidence has revealed that several piRNAs have been implicated in cancer development, though only a small number of piRNAs have been found to express in somatic tissues at present [74]. Martinez et al [74] analyzed 6, 260 human piRNA transcriptomes derived from non-malignant and tumor tissues from 11 organs and discovered that only 273 of the 20, 831 known piRNAs are expressed in somatic non-malignant tissues and 522 piRNAs are expressed in corresponding tumor tissues, with a cancer-type specific manner.…”

“…Accumulating evidence has revealed that several piRNAs have been implicated in cancer development, though only a small number of piRNAs have been found to express in somatic tissues at present [74]. Martinez et al [74] analyzed 6, 260 human piRNA transcriptomes derived from non-malignant and tumor tissues from 11 organs and discovered that only 273 of the 20, 831 known piRNAs are expressed in somatic non-malignant tissues and 522 piRNAs are expressed in corresponding tumor tissues, with a cancer-type specific manner. Altogether, piRNAs are involved in cancer cell proliferation, apoptosis, metastasis, invasion, and may be as potential prognostic and diagnostic biomarkers during cancer development (Table 1).…”

HPV status is associated with altered PIWI-interacting RNA expression pattern in head and neck cancer

“…While initial studies have shown that HPV infection affects the expression of some small non-coding RNAs, such as miRNAs, its effect on piRNA expression is unknown. The association of piRNA with patient outcome has been previously demonstrated in other cancer types, such as breast and gastric, among others 16,17,19 . Thus, it is of great relevance to characterize changes in piRNA expression patterns in the context of HPV status, as these piRNAs may represent novel predictors of clinical outcome in HPV+ HNSCC.…”

“…A custom sequence analysis pipeline was developed to deduce piRNA expression from raw sequencing data (FASTQ files) 16 . Briefly, our pipeline includes sample accrual, quality control and data quantification.…”

“…Recently, piRNA expression patterns have been shown to be deregulated in a variety of cancer types, including head and neck tumors 15-22 ; however, the relationship between piRNA expression and clinicopathological features in HNSCCs has yet to be elucidated. Interestingly, we have reported the observation of an association between piRNA expression and nodal metastasis in HNSCC 16 .…”