# Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer

**Authors:** Ryosuke Hirai, Hideaki Kinugasa, Shumpei Yamamoto, Soichiro Ako, Koichiro Tsutsumi, Makoto Abe, Koji Miyahara, Masahiro Nakagawa, Motoyuki Otsuka

PMC · DOI: 10.1038/s41416-024-02654-2 · 2024-03-27

## TL;DR

This study shows that analyzing DCC gene methylation in saliva can non-invasively detect early-stage hypopharyngeal cancer.

## Contribution

The study introduces DCC gene methylation in saliva as a novel non-invasive biomarker for superficial hypopharyngeal cancer detection.

## Key findings

- DCC methylation in saliva achieved 82.8% sensitivity and 90.2% specificity for detecting hypopharyngeal cancer.
- DCC methylation had a higher diagnostic accuracy (AUC 0.917) compared to EDNRB and ECAD in saliva samples.
- Significant methylation differences were observed in DCC, EDNRB, and ECAD between cancerous and non-cancerous tissues.

## Abstract

Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients.

Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of DCC, PTGDR1, EDNRB, and ECAD, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR.

Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of DCC (p = 0.003), EDNRB (p = 0.001), and ECAD (p = 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples, DCC showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864–0.970), compared with those for EDNRB (0.680) and ECAD (0.639). When the cutoff for the methylation values of DCC was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%.

DCC methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients.

## Linked entities

- **Genes:** DCC (DCC netrin 1 receptor) [NCBI Gene 1630], PTGDR (prostaglandin D2 receptor) [NCBI Gene 5729], EDNRB (endothelin receptor type B) [NCBI Gene 1910], CDH1 (cadherin 1) [NCBI Gene 999]
- **Diseases:** hypopharyngeal cancer (MONDO:0005216)

## Full-text entities

- **Genes:** EDNRB (endothelin receptor type B) [NCBI Gene 1910] {aka ABCDS, ET-B, ET-BR, ETB, ETB1, ETBR}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, PTGDR (prostaglandin D2 receptor) [NCBI Gene 5729] {aka AS1, ASRT1, DP, DP1, PTGDR1}, DCC (DCC netrin 1 receptor) [NCBI Gene 1630] {aka CRC18, CRCR1, HGPPS2, IGDCC1, MRMV1, NTN1R1}
- **Diseases:** hypopharyngeal cancer (MESH:D007012), cancer (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11091138/full.md

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Source: https://tomesphere.com/paper/PMC11091138