Diagnostic power of DNA methylation markers suggestive of cholangiocarcinoma in ERCP-based brush cytology

Prachayakul, Varayu; Rugivarodom, Manus; Nopjaroonsri, Papatsakorn; Cheirsilpa, Kunsuda; Chang, Arunchai; Kamolhan, Thanpawee; Boonyaarunnate, Thiraphon; Thuwajit, Chanitra; Thuwajit, Peti

doi:10.1016/j.gie.2021.07.005

Cited by 8 publications

(8 citation statements)

References 22 publications

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“…Numerous clinical trials have been conducted on the HOXA genes, but none have focused exclusively on the HOXA2 gene. Recently, the methylation level of HOXA1 was used to accurately differentiate between cholangiocarcinoma and benign biliary stricture from brushed biliary samples in clinical trial NCT04568512 [ 58 ]. HOXA9 is among the biomarkers studied in the myeloid leukaemia clinical trial NCT03701295.…”

Section: Discussionmentioning

confidence: 99%

Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K

Baharudin

Ishak

Yusof³

et al. 2022

Diagnostics

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The aims were to profile the DNA methylation in colorectal cancer (CRC) and to explore cancer-specific methylation biomarkers. Fifty-four pairs of CRCs and the adjacent normal tissues were subjected to Infinium Human Methylation 450K assay and analysed using ChAMP R package. A total of 26,093 differentially methylated probes were identified, which represent 6156 genes; 650 probes were hypermethylated, and 25,443 were hypomethylated. Hypermethylated sites were common in CpG islands, while hypomethylated sites were in open sea. Most of the hypermethylated genes were associated with pathways in cancer, while the hypomethylated genes were involved in the PI3K-AKT signalling pathway. Among the identified differentially methylated probes, we found evidence of four potential probes in CRCs versus adjacent normal; HOXA2 cg06786372, OPLAH cg17301223, cg15638338, and TRIM31 cg02583465 that could serve as a new biomarker in CRC since these probes were aberrantly methylated in CRC as well as involved in the progression of CRC. Furthermore, we revealed the potential of promoter methylation ADHFE1 cg18065361 in differentiating the CRC from normal colonic tissue from the integrated analysis. In conclusion, aberrant DNA methylation is significantly involved in CRC pathogenesis and is associated with gene silencing. This study reports several potential important methylated genes in CRC and, therefore, merit further validation as novel candidate biomarker genes in CRC.

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Section: Discussionmentioning

confidence: 99%

Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K

Baharudin

Ishak

Yusof³

et al. 2022

Diagnostics

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“…In a study using the methylation indices of HOXA1 and NEUROG1 gene promoters on samples obtained by brush cytology, the sensitivity was reported to be 95.1% (HOXA1) and 90.2% (NEUROG1) versus the 61.5% for conventional cytology alone. 42 Immunostaining the oncofetal protein insulin-like growth factor II mRNA binding protein 3 (IMP3) has been reported to be useful. When using cytoplasmic-positive staining for IMP3 as a marker of malignancy, the sensitivity and specificity reached 79.4% and 91.7%, respectively.…”

Section: Pathological Diagnosismentioning

confidence: 99%

“…Various methods for increasing the sensitivity of brush cytology and transpapillary forceps biopsy have also been reported. In a study using the methylation indices of HOXA1 and NEUROG1 gene promoters on samples obtained by brush cytology, the sensitivity was reported to be 95.1% ( HOXA1 ) and 90.2% ( NEUROG1 ) versus the 61.5% for conventional cytology alone 42 . Immunostaining the oncofetal protein insulin‐like growth factor II mRNA binding protein 3 (IMP3) has been reported to be useful.…”

Section: Diagnosismentioning

confidence: 99%

Endoscopic management of perihilar cholangiocarcinoma

Kawashima

Ohno

Ishikawa

et al. 2022

Digestive Endoscopy

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Endoscopic management for perihilar cholangiocarcinoma (PHCC) is evolving toward more accurate diagnosis and safer drainage. In imaging, it is important to diagnose the entire lesion using multidetector‐row computed tomography to determine resectability and optimal surgical planning, followed by local diagnosis using endoscopic retrograde cholangiopancreatography. Video peroral cholangioscopy and probe‐based confocal laser endomicroscopy have been newly introduced as diagnostic imaging methods and are being applied clinically. In transpapillary forceps biopsy for PHCC diagnosis, the location in the bile duct (for mapping biopsy) and the number of biopsy samples should be determined depending on resectability, the morphological type, and future surgical planning. Preoperative drainage has shifted from percutaneous transhepatic biliary drainage to endoscopic nasobiliary drainage given the possibility of seeding metastasis. In addition, considering potential patient discomfort from a nasal tube, the usefulness of the placement of a plastic stent above the papilla (inside stent) as a bridging therapy for surgery has been reported. For drainage of unresectable PHCC, the improved prognosis due to advances in chemotherapy has necessitated a strategy that accounts for reintervention. Thus, in addition to uncovered self‐expandable metallic stents (SEMS), exchangeable slim fully covered SEMS and inside stents have started to be used. In addition to the conventional transpapillary approach, an endoscopic ultrasonography‐guided approach has been introduced, and a combination of both methods has also been proposed. To improve the quality of life and prognosis of PHCC patients, endoscopists need to understand and be able to use the various methods of endoscopic management for PHCC.

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“…Andersen et al suggested that a four-gene panel, namely, CDO1, CNRIP1, SEPT9, and VIM, detected in 45%-77% of the samples had a sensitivity and specificity of 85% and 98%, respectively (83). Prachayakul et al reported using the methylation index (MI) of two genes, HOXA1 and NEUROG1 (84). Each has better sensitivity and accuracy than cytology and CA 19-9 in differentiating CCA from benign diseases.…”

Section: Somatic Mutations In Blood Bile and Cytology Specimens In Biliary Tract Cancermentioning

confidence: 99%

“…Prachayakul et al. reported using the methylation index (MI) of two genes, HOXA1 and NEUROG1 ( 84 ). Each has better sensitivity and accuracy than cytology and CA 19-9 in differentiating CCA from benign diseases.…”

Section: Precision Medicine In Biliary Tract Cancer: Current State and Future Directionsmentioning

confidence: 99%

Biliary Tract Cancers: Treatment Updates and Future Directions in the Era of Precision Medicine and Immuno-Oncology

et al. 2021

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The effective management of biliary tract cancers (BTCs) has been hampered by limited options for systemic therapy. In recent years, the focus on precision medicine has made technologies such as next-generation sequencing (NGS) accessible to clinicians to identify targetable mutations in BTCs in tumor tissue (primarily) as well as blood, and to treat them with targeted therapies when possible. It has also expanded our understanding of functional pathways associated with genetic alterations and opened doors for identifying novel targets for treatment. Recent advances in the precision medicine approach allowed us to identify new molecular markers in BTCs, such as epigenetic changes (methylation and histone modification) and non-DNA markers such as messenger RNA, microRNA, and long non-coding RNA. It also made detecting these markers from non-traditional sources such as blood, urine, bile, and cytology (from fine-needle aspiration and biliary brushings) possible. As these tests become more accessible, we can see the integration of different molecular markers from all available sources to aid physicians in diagnosing, assessing prognosis, predicting tumor response, and screening BTCs. Currently, there are a handful of approved targeted therapies and only one class of immunotherapy agents (immune checkpoint inhibitors or ICIs) to treat BTCs. Early success with new targets, vascular endothelial growth factor receptor (VEGFR), HER2, protein kinase receptor, and Dickkopf-1 (DKK1); new drugs for known targets, fibroblast growth factor receptors (FGFRs) such as futabatinib, derazantinib, and erdafitinib; and ICIs such as durvalumab and tremelimumab is encouraging. Novel immunotherapy agents such as bispecific antibodies (bintrafusp alfa), arginase inhibitors, vaccines, and cellular therapy (chimeric antigen receptor—T cell or CAR-T, natural killer cells, tumor-infiltrating lymphocytes) have the potential to improve outcomes of BTCs in the coming years.

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Diagnostic power of DNA methylation markers suggestive of cholangiocarcinoma in ERCP-based brush cytology

Cited by 8 publications

References 22 publications

Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K

Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K

Endoscopic management of perihilar cholangiocarcinoma

Biliary Tract Cancers: Treatment Updates and Future Directions in the Era of Precision Medicine and Immuno-Oncology

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