Wei Zhang1, Maowei Ni2, Ying Su3, Hua Wang1, Shaoxin Zhu1, An Zhao4, Guorong Li5. 1. Department of Urology, Zhejiang Cancer Hospital, Hang Zhou, China. 2. Institute of Cancer Research, Zhejiang Cancer Hospital, Hang Zhou, China. 3. Department of Pathology, Zhejiang Cancer Hospital, Hang Zhou, China. 4. Department of Urology, Zhejiang Cancer Hospital, Hang Zhou, China; Institute of Cancer Research, Zhejiang Cancer Hospital, Hang Zhou, China. Electronic address: anzmxx@gmail.com. 5. Department of Urology, North Hospital, CHU Saint-Etienne, University of Jean-Monnet, Saint-Etienne, France; Inserm U1059, Saint-Etienne, France. Electronic address: grli2001@yahoo.fr.
Abstract
BACKGROUND: Circulating microRNAs (miRNAs) in exosomes are emerging as clinically useful tools for cancer detection. However, little is known about their diagnostic impact in clear-cell renal cell carcinoma (ccRCC). OBJECTIVE: To investigate whether miRNAs in serum exosomes can serve as biomarkers in ccRCC. DESIGN, SETTING, AND PARTICIPANTS: Serum samples were obtained from 82 patients with ccRCC and 80 healthy volunteers. Exosomes were extracted and purified to selectively capture exosomes positive for tumor-associated epithelial cell adhesion molecule (EpCAM) via a magnetic bead technique. Total RNA was extracted and expression levels of miR-210, miR-1233, and miR-15a miRNAs were quantified and normalized to U6 levels. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Expression levels were compared using a Mann-Whitney U-test, Friedman test, or Wilcoxon test. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value of exosomal miRNAs for differentiation between ccRCC patients and controls. RESULTS AND LIMITATIONS: Expression levels of exosomal miR-210 and miR-1233 were significantly higher in ccRCC patients than in healthy individuals (both p<0.01). No significant difference was observed for exosomal miR-15a. Exosomal miR-210 and miR-1233 expression levels in different TNM stages were significantly higher than in the controls (all p<0.01). Exosomal miR-210 and miR-1233 expression levels were significantly lower in postoperative than in preoperative samples (both p<0.01). ROC analysis demonstrated that exosomal expression levels distinguished ccRCC patients from healthy individuals with 70% sensitivity and 62.2% specificity for miR-210, and 81% sensitivity and 76% specificity for miR-1233. The retrospective design and lack of other tumor subtypes are limitations of the study. CONCLUSIONS: Serum exosomal miRNAs might represent potential diagnostic biomarkers in ccRCC in the future. PATIENT SUMMARY: Circulating levels of exosomal microRNAs miR-210 and miR-1233 have potential as biomarkers for diagnostic and monitoring purposes in renal cancer in the future. These molecules can be measured in serum in so-called liquid biopsy.
BACKGROUND: Circulating microRNAs (miRNAs) in exosomes are emerging as clinically useful tools for cancer detection. However, little is known about their diagnostic impact in clear-cell renal cell carcinoma (ccRCC). OBJECTIVE: To investigate whether miRNAs in serum exosomes can serve as biomarkers in ccRCC. DESIGN, SETTING, AND PARTICIPANTS: Serum samples were obtained from 82 patients with ccRCC and 80 healthy volunteers. Exosomes were extracted and purified to selectively capture exosomes positive for tumor-associated epithelial cell adhesion molecule (EpCAM) via a magnetic bead technique. Total RNA was extracted and expression levels of miR-210, miR-1233, and miR-15a miRNAs were quantified and normalized to U6 levels. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Expression levels were compared using a Mann-Whitney U-test, Friedman test, or Wilcoxon test. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value of exosomal miRNAs for differentiation between ccRCC patients and controls. RESULTS AND LIMITATIONS: Expression levels of exosomal miR-210 and miR-1233 were significantly higher in ccRCC patients than in healthy individuals (both p<0.01). No significant difference was observed for exosomal miR-15a. Exosomal miR-210 and miR-1233 expression levels in different TNM stages were significantly higher than in the controls (all p<0.01). Exosomal miR-210 and miR-1233 expression levels were significantly lower in postoperative than in preoperative samples (both p<0.01). ROC analysis demonstrated that exosomal expression levels distinguished ccRCC patients from healthy individuals with 70% sensitivity and 62.2% specificity for miR-210, and 81% sensitivity and 76% specificity for miR-1233. The retrospective design and lack of other tumor subtypes are limitations of the study. CONCLUSIONS: Serum exosomal miRNAs might represent potential diagnostic biomarkers in ccRCC in the future. PATIENT SUMMARY: Circulating levels of exosomal microRNAs miR-210 and miR-1233 have potential as biomarkers for diagnostic and monitoring purposes in renal cancer in the future. These molecules can be measured in serum in so-called liquid biopsy.
Authors: Ghislaine Scelo; David C Muller; Elio Riboli; Mattias Johansson; Amanda J Cross; Paolo Vineis; Konstantinos K Tsilidis; Paul Brennan; Heiner Boeing; Petra H M Peeters; Roel C H Vermeulen; Kim Overvad; H Bas Bueno-de-Mesquita; Gianluca Severi; Vittorio Perduca; Marina Kvaskoff; Antonia Trichopoulou; Carlo La Vecchia; Anna Karakatsani; Domenico Palli; Sabina Sieri; Salvatore Panico; Elisabete Weiderpass; Torkjel M Sandanger; Therese H Nøst; Antonio Agudo; J Ramón Quirós; Miguel Rodríguez-Barranco; Maria-Dolores Chirlaque; Timothy J Key; Prateek Khanna; Joseph V Bonventre; Venkata S Sabbisetti; Rupal S Bhatt Journal: Clin Cancer Res Date: 2018-07-23 Impact factor: 12.531