Abstract

Simple SummaryAround 30% of men treated with adjuvant therapy experience recurrences of prostate cancer (PC). Current monitoring of the relapse of PC requires regular postoperative prostate-specific antigen (PSA) value follow-up. Our study aims to identify potential multiomics biomarkers using modern computational analytic methods, deep learning (DL), similarity network fusion (SNF), and the Cancer Genome Atlas (TCGA) prostate adenocarcinoma (PRAD) dataset. Six significantly intersected omics biomarkers from the two models, TELO2, ZMYND19, miR-143, miR-378a, cg00687383 (MED4), and cg02318866 (JMJD6; METTL23) were collected for multiomics panel construction. The difference between the Kaplan–Meier curves of high and low recurrence-risk groups generated from the multiomics panels and clinical information achieve p-value = 2.97 × 10−15 and C-index = 0.713, and the prediction performance of five-year recurrence achieves AUC = 0.789. The results show that the multiomics panel provided valuable biomarkers for the early detection of high-risk recurrent patients, and integrating multiomics data gave us the power to detect the complex mechanisms of cancer among the interactions of different genetic and epigenetic factors.This study is to identify potential multiomics biomarkers for the early detection of the prognostic recurrence of PC patients. A total of 494 prostate adenocarcinoma (PRAD) patients (60-recurrent included) from the Cancer Genome Atlas (TCGA) portal were analyzed using the autoencoder model and similarity network fusion. Then, multiomics panels were constructed according to the intersected omics biomarkers identified from the two models. Six intersected omics biomarkers, TELO2, ZMYND19, miR-143, miR-378a, cg00687383 (MED4), and cg02318866 (JMJD6; METTL23), were collected for multiomics panel construction. The difference between the Kaplan–Meier curves of high and low recurrence-risk groups generated from the multiomics panel achieved p-value = 5.33 × 10−9, which is better than the former study (p-value = 5 × 10−7). Additionally, when evaluating the selected multiomics biomarkers with clinical information (Gleason score, age, and cancer stage), a high-performance prediction model was generated with C-index = 0.713, p-value = 2.97 × 10−15, and AUC = 0.789. The risk score generated from the selected multiomics biomarkers worked as an effective indicator for the prediction of PRAD recurrence. This study helps us to understand the etiology and pathways of PRAD and further benefits both patients and physicians with potential prognostic biomarkers when making clinical decisions after surgical treatment.

Highlights

  • Prostate cancer (PC) is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide, with a rapidly rising number of patients in the past few decades

  • We propose modern computational analytical methods, the autoencoder model, as our adopted Deep learning (DL) algorithm, and similarity network fusion (SNF) to create a comprehensive view of the connections among methylation-related gene expressions, microRNA, and gene expressions, and differentiate patients at a high risk of recurrence with the prediction model to better predict the prognosis of PC

  • The results showed that there are 21 genes (LSM7, PAXX, PPP1R35, MHENCR, PSMG3, ATP5MPL, POLR2H, TELO2, PFDN6, PLEKHJ1, STX10, ZMYND19, FYCO1, PARVA, NFE2L2, MBNL2, LPP, ELF1, RNF185, IL6ST, PARM1), 3 methylation-related genes (cg00687383 (MED4), cg02318866 (JMJD6; METTL23), cg02978959 (CTC-444N24.6; ZNF460)

Read more

Summary

Introduction

Prostate cancer (PC) is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide, with a rapidly rising number of patients in the past few decades. Based on GLOBOCAN 2018 estimates [1], 1,276,106 new cases of PC were reported globally in 2018, with higher prevalence in developed countries. According to an estimate by the American Cancer Society [2], there were about 191,930 new cases of PC and about 33,330 deaths from PC in 2020 in the U.S. At present, standard treatments of PC include a prostatectomy, radiation therapy, or both. Standard treatments of PC include a prostatectomy, radiation therapy, or both Despite these aggressive approaches, 25–40% of treated men experience recurrences of PC [3]. R factors associated with PC recurrence include the prostate-specific antigen (PSA) level in serum, the Gleason score of the prostate specimen, the patient’s age, and the cancer stage. The most common early sign of recurrent PC is a rising serum PSA level

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call