Serum RNA Profiling in the 10-Years Period Prior to Diagnosis of Testicular Germ Cell Tumor.

Joshua Burton,Sinan U Umu,Trine B Rounge,Hilde Langseth,Tom Grotmol,Tom K Grimsrud,Trine B Haugen

doi:10.3389/fonc.2020.574977

Abstract

Although testicular germ cell tumor (TGCT) overall is highly curable, patients may experience late effects after treatment. An increased understanding of the mechanisms behind the development of TGCT may pave the way for better outcome for patients. To elucidate molecular changes prior to TGCT diagnosis we sequenced small RNAs in serum from 69 patients who were later diagnosed with TGCT and 111 matched controls. The deep RNA profiles, with on average 18 million sequences per sample, comprised of nine classes of RNA, including microRNA. We found that circulating RNA signals differed significantly between cases and controls regardless of time to diagnosis. Different levels of TSIX related to X-chromosome inactivation and TEX101 involved in spermatozoa production are among the interesting findings. The RNA signals differed between seminoma and non-seminoma TGCT subtypes, with seminoma cases showing lower levels of RNAs and non-seminoma cases showing higher levels of RNAs, compared with controls. The differentially expressed RNAs were typically associated with cancer related pathways. Our results indicate that circulating RNA profiles change during TGCT development according to histology and may be useful for early detection of this tumor type.

Highlights

Testicular germ cell tumor (TGCT) is diagnosed in 1% of men worldwide and is the most common malignancy in males between 20 and 39 years of age
We found the RNA profiles in pre-diagnostic serum of TGCT patients to be different from that of controls, and observed that the difference was relatively stable across the pre-diagnostic time period of 10 years
Previous studies have identified TGCT specific RNA profiles in patients [28,29,30], this has not been described for the pre-diagnostic period, as seen in our study

Summary

Introduction

Testicular germ cell tumor (TGCT) is diagnosed in 1% of men worldwide and is the most common malignancy in males between 20 and 39 years of age. The susceptibility to TGCT is shown to have a strong familial link, with a fourfold increased risk for fathers and eightfold for brothers [4, 5]. The polygenic nature of TGCT has been recognized and more than 50 susceptibility genes have been identified [6,7,8,9]. The susceptibility loci contain genes linked to germ cell development and sex determination, as well as genes related to tumor growth/suppression. Cryptorchidism is a well-known risk factor, and around 10% of males with TGCT have a history of cryptorchidism [10]. The main histologic subtypes of TGCT are seminoma, non-seminoma and mixed, making up around 50, 30, and 20%, respectively [11]

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