Po-Hsuan Su

Shuang Ho Hospital · Translational Epigenetics Center

Window of implantation (WOI) genes have been comprehensively identified at the single cell level. DNA methylation changes in cervical secretions are associated with in vitro fertilization embryo transfer (IVF-ET) outcomes. Using a machine learning (ML) approach, we aimed to determine which methylation changes in WOI genes from cervical secretions b...

The causes of implantation failure remain a black box in reproductive medicine. The exact mechanism behind the regulation of endometrial receptivity is still unknown. Epigenetic modifications influence gene expression patterns and may alter the receptivity of human endometrium. Cervical secretions contain endometrial genetic material, which can be...

Objectives DNA methylation arrays and MethylCap-sequencing data of endometrial tissues from our previous study found that BHLHE22 gene promoter was hypermethylated in endometrial cancer (EC) and combine with CDO1 promoter hypermethylation had been approved by Taiwan FDA to detect EC in early stage using endocervical sample. BHLHE22 is literally a b...

Background: We describe a DNA methylation assay, named MPap test, using cervical scraping as an alternative technique for endometrial cancer detection. Methods: A multicenter hospital-based, two-stage validation study was conducted to validate the cancer detection performance of the MPap test. The MPap value was determined from the DNA methylati...

Endometrial cancer (EC) rates are rising annually. Additional prediction markers need to be evaluated because only 10–20% of EC cases show an objective response to immune-checkpoint inhibitors (ICIs). Our previous methylomic study found that BHLHE22 is hypermethylated in EC tissues and can be detected using a Pap-smear sample. BHLHE22, a basic heli...

Adenomyosis is linked to dysmenorrhea and infertility. The pathogenesis of adenomyosis remains unclear, and little is known of the genetic and epigenetic changes in the eutopic endometrium in adenomyosis, which may predispose patients to the invasion and migration of endometrial tissues into the myometrium. Transcriptome studies have identified gen...

Intraperitoneal metastasis is a challenging clinical scenario in epithelial ovarian cancer (EOC). As they are distinct from hematogenous metastasizing tumors, epithelial ovarian cancer cells primarily disseminate within the peritoneal cavity to form superficially invasive carcinomas. Unfavorable pharmacokinetics for peritoneal tumors and gut toxici...

Gynecological cancer is a grave threat to women’s health. The human papillomavirus (HPV) infection is the main risk of cervical cancer. The incidence and mortality of cervical cancer have gradually decreased since the clinical use of pap smears. However, the sensitivity of pap smears still varies with different screening equipment, which seriously...

Objective To study whether the methylation status of cervical secretions can reflect the ability of the endometrium to allow embryo implantation. Design Case-control study. Setting In vitro fertilization centers. Patient(s) Women undergoing embryo transfer cycles, in which at least one good-quality embryo was transferred. Intervention(s) Collec...

Background Leiomyosarcoma (LMS), the most common soft tissue sarcoma, exhibits heterogeneous and complex genetic karyotypes with severe chromosomal instability and rearrangement and poor prognosis. Methods Clinical variables associated with NKX6-1 were obtained from The Cancer Genome Atlas (TCGA). NKX6-1 mRNA expression was examined in 49 human ut...

Background: Endometrial cancer is a common gynecologic cancer. Noninvasive molecular biomarkers for triage of high-risk patients for invasive procedures are needed. Based on the success of cytological Pap smear screening, cervical scrapings are a good source of DNA for molecular testing. In addition to genetic lesions, DNA methylation is a promisi...

Background: Ovarian cancer (OC) is the most lethal gynecological cancer, worldwide, largely due to its vague and nonspecific early stage symptoms, resulting in most tumors being found at advanced stages. Moreover, due to its relative rarity, there are currently no satisfactory methods for OC screening, which remains a controversial and cost-prohib...

DNA methylation alteration, such as global hypomethylation and localized hypermethylation, within the promoters of tumor suppressor genes, is an important risk factor in cervical cancer. The potential use of DNA methylation detection, in cervical cancer screening or triage of mildly abnormal cytology, has recently been demonstrated. In particular,...

Ten‐eleven translocation methylcytosine dioxygenase‐1, TET1, takes part in active DNA demethylation. However, our understanding of DNA demethylation in cancer biology and its clinical significance remain limited. This study showed that TET1 expression correlated with poor survival in advanced‐stage epithelial ovarian carcinoma (EOC), and with cell...

Ovarian high‐grade serous carcinoma (HGSC) is the most lethal gynecological malignancy. Prevailing evidences suggest that drug resistance and recurrence of ovarian HGSC are caused by the presence of cancer stem cells. Therefore, targeting cancer stems is appealing, however, all attempts to date, have failed. To circumvent this limit, we analyzed di...

Precision medicine requires markers for therapeutic guidance. The purpose of this study was to determine whether epithelial ovarian cancer (EOC) epigenetics can lead to the identification of biomarkers for precision medicine. Through integrative methylomics, we discovered and validated the epigenetic signature of NEFH and HS3ST2 as an independent p...

Pyruvate kinase M2 (PKM2) regulates glycolysis and oxidative phosphorylation; however, the role of PKM2 in ovarian cancer remains largely unknown. We investigated whether ovarian cancer metabolism could provide insight into the development of therapeutic strategies. We performed immunohistochemical staining for PKM2 on a tissue microarray for multi...

Objective Hypermethylation of human papillomavirus (HPV) and host genes has been reported in cervical cancer. However, the degree of methylation of different HPV types relative to the severity of the cervical lesions remains controversial. Studies of the degree of methylation associated with the host gene and the HPV genome to the severity of cervi...

Demographics related to the clinical samples

Methylation level of HPV L1 region in patients and control subjects

The distribution of CpG sites in 4 HPV types. The location of CpG sites and genes shown on each HPV genome by IGV. The arrows indicate regions where methylation was detected. (A) HPV16. (B) HPV18. (C) HPV52. (D) HPV58.

The epigenetic aspects of the HPV genome. We hypothesized that different HPV genotypes may have different effects on the host epigenetic machinery. In HPV16, the host methylation machinery is triggered strongly to methylate the viral and host genome. In HPV52, the viral genome methylation is accompanied by less methylation of host gene.

The attempts of target therapy in ovarian cancer therapy mostly fail. There is a need of biomarkers for better patient stratification in clinical trials. Epigenetics is a driving force for cancer development and may serve as a molecular marker of disease. The present study was to analyze the clinical relevance of methylation phenotypes and figure o...

Epigenetic dysregulation is important in cervical cancer development, but the underlying mechanism is largely unknown. Increasing evidence indicates that DNA methylation is sensitive to changes in microenvironmental factors, such as nitric oxide (NO) in the chronic inflammatory cervix. However, the epigenomic effects of NO in cancer have not been i...

Purpose: Endometrial cancer (EC) is a common gynecological cancer whose incidence is increasing annually worldwide. Current methods to detect EC are unreliable and biomarkers are unsatisfactory for screening. Cervical scrapings were reported as a potential source of material for molecular testing. DNA methylation is a promising cancer biomarker, b...

Ovarian cancer treatment remains a challenge and targeting cancer stem cells presents a promising strategy. Niclosamide is an "old" antihelminthic drug that uncouples mitochondria of intestinal parasites. Although recent studies demonstrated that niclosamide could be a potential anticancer agent, its poor water solubility needs to be overcome befor...

Insufficient specificity of the high-risk human papillomavirus (hrHPV) assay in primary cervical cancer screening results in unnecessary referral. Additional assays to triage hrHPV-positive women are needed to improve molecular cervical cancer screening. DNA methylation is a promising biomarker in cervical cancer. We evaluated the clinical performa...

Non-attendance at gynecological clinics is a major limitation of cervical cancer screening and self-collection of samples may improve this situation. Although HPV testing of self-collected vaginal samples is acceptable, the specificity is inadequate. The current focus is increasing self-collection of vaginal samples to minimize clinic visits. In th...

Using DNA methylation biomarkers in cancer detection is a potential direction in clinical testing. Some methylated genes have been proposed for cervical cancer detection; however, more reliable methylation markers are needed. To identify new hypermethylated genes in the discovery phase, we compared the methylome between a pool of DNA from normal ce...

DNA methylation contributes to tumor formation, development and metastasis. Epigenetic dysregulation of stem cells is thought to predispose to malignant development. The clinical significance of DNA methylation in ovarian tumor-initiating cells (OTICs) remains unexplored. We analyzed the methylomic profiles of OTICs (CP70sps) and their derived prog...

Despite of the trend that the application of DNA methylation as a biomarker for cancer detection is promising, clinically applicable genes are few. Therefore, we looked for novel hypermethylated genes for cervical cancer screening. At the discovery phase, we analyzed the methylation profiles of human cervical carcinomas and normal cervixes by methy...

Genes re-expression analysis by QRT-PCR in cervical cell lines. (TIF)

The intensity of probes by MeDIP-on-chip for thirty-two regions (including 35 genes) in cervical tissue. (TIF)

Demographic for discovery and pre-validation phase studies. (PDF)

Selected 192 methylated genes in SCC and AC. (PDF)

The summary of polymerase chain reaction primers. (PDF)

(DOC)

The role of aldehyde dehydrogenase 1 (ALDH1) as an ovarian cancer stem cell marker and its clinical significance have rarely been explored. We used an Aldefluor assay to isolate ALDH1-bright (ALDH1(br)) cells from epithelial ovarian cancer cell lines and characterized the properties of the stem cells. ALDH1(br) cells were enriched in ES-2 (1.3%), T...

Epigenetic modifications are a driving force in carcinogenesis. However, their role in cancer metastasis remains poorly understood. The present study investigated the role of DNA methylation in the cervical cancer metastasis. Here, we report evidence of the overexpression of DNA methyltransferases 3B (DNMT3B) in invasive cervical cancer and of the...

Introduction: Epigenetic modifications are a driving force in carcinogenesis. In addition to its role in initiation and promotion, DNA methylation is thought to participate in cancer metastasis. The present study is to interrogate the role of de novo DNA methylation in cervical cancer invasions. Methods and Results: Here, we report evidence of the...

DNA methylation may be used a potential biomarker for detecting cervical cancer. The authors of this report used quantitative methylation analysis of 4 genes in a full spectrum of cervical lesions to test its potential clinical application. This hospital-based, retrospective, case-control study was conducted in 185 patients and included patients wh...

DNA methylation is important in cancer development and is a promising biomarker for cancer detection. An epigenomic approach used in our previous work showed that LMX-1A is methylation-silenced in cervical cancer. LMX-1A, a LIM-homeobox gene, is known to participate in developmental events; however, there are at present no data on the role of LMX-1...