Serum PIWI-Interacting RNAs piR-020619 and piR-020450 Are Promising Novel Biomarkers for Early Detection of Colorectal Cancer

Abstract

Background: Early diagnosis can significantly reduce colorectal cancer deaths. We sought to identify serum PIWI-interacting RNAs (piRNAs) that could serve as sensitive and specific noninvasive biomarkers for early colorectal cancer detection.Methods: We screened the piRNA expression profile in sera from 7 patients with colorectal cancer and 7 normal controls using small RNA sequencing. Differentially expressed piRNAs were measured in a training cohort of 140 patients with colorectal cancer and 140 normal controls using reverse transcription quantitative PCR. The identified piRNAs were evaluated in two independent validation cohorts of 180 patients with colorectal cancer and 180 normal controls. Finally, the diagnostic value of the identified piRNAs for colorectal adenoma (CRA) was assessed, and their expression was measured in 50 patients with lung cancer, 50 with breast cancer, and 50 with gastric cancer. Results:The piRNAs piR-020619 and piR-020450 were consistently elevated in sera of patients with colorectal cancer as compared with controls. A predicative panel based on the two piRNAs was established that displayed high diagnostic accuracy for colorectal cancer detection. The two-piRNA panel could detect small-size and early-stage colorectal cancer with an area under the ROC curve of 0.863 and 0.839, respectively. Combined use of the two piRNAs could effectively distinguish CRA from controls. Aberrant elevation of the two piRNAs was not observed in sera of patients with lung, breast, and gastric cancer.Conclusions: Serum piR-020619 and piR-020450 show a strong potential as colorectal cancer-specific early detection biomarkers.Impact: The field of circulating piRNAs could allow for novel tumor biomarker development.

Circulating exosomal small RNAs are promising non‐invasive diagnostic biomarkers for gastric cancer

“…One recent study has showed that serum piR-020619 and piR-020450 are promising novel biomarkers for early detection of colorectal cancer. 16 Another study has revealed piR-13643 and piR-21238 could be novel diagnostic biomarkers for papillary thyroid carcinoma. 37 In addition, piR-10506469 were found to be significantly increased in the exosomes of plasma from both cholangiocarcinoma and gallbladder carcinoma patients, indicating it may be serve as the potential cancer biomarker.…”

“…It indicated piRNAs could be potential and powerful biomarkers for cancer diagnosis and prognosis. One recent study has showed that serum piR‐020619 and piR‐020450 are promising novel biomarkers for early detection of colorectal cancer 16 . Another study has revealed piR‐13643 and piR‐21238 could be novel diagnostic biomarkers for papillary thyroid carcinoma 37 .…”

“…Accumulating studies reveal circulating miRNAs might be useful diagnostic and prognostic biomarker for various cancer 15 . Serum piR‐020619 and piR‐020450 are promising novel biomarkers for early detection of colorectal cancer 16 . Elevating piR‐823 level could suppress the growth of GC cells 17 .…”

“…15 Serum piR-020619 and piR-020450 are promising novel biomarkers for early detection of colorectal cancer. 16 Elevating piR-823 level could suppress the growth of GC cells. 17 Another study showed that a three-piRNA cluster associated with recurrence-free survival (RFS) of patients with gastric adenocarcinoma.…”

Towards Novel Non-Invasive Colorectal Cancer Screening Methods: A Comprehensive Review

“…Three studies describing piRNAs as CRC screening tests were listed in Table S4 (Supplementary material) [ 32 , 33 , 34 ].…”