DNA Methylation as a Noninvasive Epigenetic Biomarker for the Detection of Cancer.

In light of the high incidence and mortality rates of cancer, early and accurate diagnosis is an important priority for assigning optimal treatment for each individual with suspected illness. Biomarkers are crucial in the screening of patients with a high risk of developing cancer, diagnosing patients with suspicious tumours at the earliest possible stage, establishing an accurate prognosis, and predicting and monitoring the response to specific therapies. Epigenetic alterations are innovative biomarkers for cancer, due to their stability, frequency, and noninvasive accessibility in bodily fluids.

ZIC1 is silenced and has tumor suppressor function in malignant pleural mesothelioma.

Introduction: Epigenetic inactivation of tumor suppressor genes is involved in the development of malignant pleural mesothelioma (MPM). ZIC1, a potential tumor suppressor gene involved in regulating cell growth and apoptosis, was investigated in MPM cell lines and tumors.

Methods: ZIC1 expression and promoter methylation were evaluated in MPM cell lines and tumor samples by quantitative polymerase chain reaction (PCR), Combined Bisulfite Restriction Analysis, and methylation-specific PCR.

Circulating microRNAs as specific biomarkers for breast cancer detection.

Background: We previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection.

Methodology/principal Findings: TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls.

Quantitative analysis and diagnostic significance of methylated SLC19A3 DNA in the plasma of breast and gastric cancer patients.

Background: Previously, we have examined the methylation status of SLC19A3 (solute carrier family 19, member 3) promoter and found that SLC19A3 was epigenetically down-regulated in gastric cancer. Here, we aim to develop a new biomarker for cancer diagnosis using methylated SLC19A3 DNA in plasma.

Methodology/principal Findings: SLC19A3 gene expression was examined by RT-qPCR.

Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer.

The potential anti-senescence gene Klotho (KL) has been recently found to participate in the progression of several different human cancers including breast, lung, and cervical cancer. In this current study, we identified KL as a candidate tumor suppressor gene silenced through promoter hypermethylation in colorectal cancer (CRC). KL gene expression is found to be absent or reduced in colon cancer cell lines (5/6, 83.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone promoted gastric cancer growth through prostaglandin E receptor (EP2 and EP4) in vivo and in vitro.

Prostaglandin E (EP) receptor is positively related with COX-2, which is involved in cancer biology. A mechanistic study on how 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) promotes gastric carcinogenesis is lacking. Recently, we found that nicotine promoted tumor growth through upregulation of the COX-2/prostaglandin E(2) pathway.

Activation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growth.

Nicotine is shown to be one of the carcinogenic agents for gastric cancer. Perturbation of epithelial-mesenchymal transition (EMT) results in loss of intracellular adhesions leading to tumor progression. In this study, we examined the underlying mechanism of the long-term effects of nicotine on tumor progression in human gastric cancer cells.

ZIC1 is downregulated through promoter hypermethylation in gastric cancer.

As one of major epigenetic changes responsible for tumor suppressor gene inactivation in the development of cancer, promoter hypermethylation was proposed as a marker to define novel tumor suppressor genes. In the current study we identified ZIC1 (Zic family member 1, odd-paired Drosophila homolog) as a novel tumor suppressor gene silenced through promoter hypermethylation in gastric cancer, the second leading cause of cancer death worldwide. In all of gastric cancer cells lines examined, ZIC1 expression was downregulated and such downregulation was accompanied with the hypermethylation of ZIC1 promoter.

Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and beta-adrenergic receptor signaling pathways.

Induction of cyclooxygenase-2 (COX-2) associates with cigarette smoke exposure in many malignancies. Nicotine and its derivative, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are the two important components in cigarette smoke that contributes to cancer development. However, the molecular mechanism(s) by which nicotine or NNK promotes gastric carcinogenesis remains largely unknown.