Prospective study to validate the clinical utility of DNA diagnosis of peritoneal fluid cytology test in gastric cancer.

Abstract

The clinical efficacy of DNA cytology test (CY) in gastric cancer (GC) has been retrospectively proposed using cancer-specific methylation of cysteine dioxygenase type 1 (CDO1). We confirmed the clinical utility of DNA CY in a prospective cohort. Four hundred GC samples were prospectively collected for washing cytology (UMIN000026191), and detection of the DNA methylation of CDO1 was assessed by quantitative methylation-specific PCR in the sediments. Endpoint was defined as the match rate between conventional CY1 and DNA CY1 (diagnostic sensitivity), and the DNA CY0 rate (diagnostic specificity) in pStage IA. DNA CY1 was detected in 45 cases (12.5%), while CY1 was seen in 31 cases (8.6%) of 361 chemotherapy-naïve samples, where the sensitivity and specificity of the DNA CY in the peritoneal solutions were 74.2% and 96.5%, respectively. The DNA CY was positive for 3.5/0/4.9/11.4/58.8% in pStage IA/IB/II/III/IV, respectively (P < .01). In the multivariate analysis, DNA CY1 was independently correlated with pathological tumor depth (pT) (P = .0012), female gender (P = .0099), CY1 (P = .0135), P1 (P = .019), and carcinoembryonic antigen (CEA) (P = .036). The combination of DNA CY1 and P factor nearly all covered the potential peritoneal dissemination (P1 and/or CY1 and/or DNA CY1) (58/61:95.1%). DNA CY1 had a significantly poorer prognosis than DNA CY0 in GC patients (P < .0001). DNA CY1 detected by CDO1 promoter DNA methylation has a great value to detect minimal residual disease of the peritoneum in GC clinics, representing poor prognosis as a novel single DNA marker.

• Authors: Hiroki Harada, Takafumi Soeno, Nobuyuki Nishizawa, Marie Washio, Mikiko Sakuraya, Hideki Ushiku, Masahiro Niihara, Kei Hosoda, Yusuke Kumamoto, Takeshi Naitoh, Takafumi Sangai, Naoki Hiki, Keishi Yamashita
• Journal: Cancer science (Cancer Sci) Vol. 112 Issue 4 Pg. 1644-1654 (Apr 2021) ISSN: 1349-7006 [Electronic] England
• PMID: 33576114 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Biomarkers, Tumor
• DNA
• Cysteine Dioxygenase

Topics

• Aged
• Ascitic Fluid (pathology)
• Biomarkers, Tumor (genetics)
• Cysteine Dioxygenase (genetics)
• Cytodiagnosis (methods)
• DNA (genetics)
• DNA Methylation (genetics)
• Female
• Humans
• Male
• Neoplasm Staging (methods)
• Peritoneal Neoplasms (diagnosis, genetics, pathology)
• Peritoneum (pathology)
• Prognosis
• Promoter Regions, Genetic (genetics)
• Prospective Studies
• Stomach Neoplasms (diagnosis, genetics, pathology)