| 摘要: | The mortality rate of colorectal cancer (CRC) is the second rate in worldwide and it ranks the third in terms of cancerous incidence. Early detection and diagnosis are crucial in lowering CRC-related mortality rate, reduced the incidence and better patient outcomes. The stability of epigenetic alteration is considered a potential biomarker. This study aims to characterize the alteration pattern of mothers against decapentaplegic homolog 3 (SMAD3) in colorectal cancer (CRC) patients and its applications in early detection. Tissues, polyps, and plasma were collected from Taipei Medical University Joint Biobank and Taipei Veterans General Hospital. In this study, we performed Genomic DNA, circulating cell-free (ccf) DNA and RNA extraction, Quantitative reverse-transcription polymerase chain reaction (qRT-PCR), TaqMan quantitative methylation-specific PCR (MSP), Genome-wide methylation analysis to analyze the relationship with SMAD3 methylation. The qMSP revealed that hypomethylated SMAD3 occurs in 91.4% and 66.6% of the tumor and benign tubular adenomas polyps tissues of Taiwanese CRC, respectively. Moreover, the hypomethylation of circulating cell-free methylation SMAD3 was found to have a sensitivity of 86.6% and specificity of 40 % in manual DNA extraction. In addition, automatic DNA extraction was found to have a sensitivity of 70 % and 80 % specificity. A poor survival rate was found in the SMAD3 hypomethylation group, especially among the Taiwanese elderly, late-stage CRC, and males. SMAD3 mRNA expression was lower in tumor tissue and benign tubular adenomas polyps. Pearson correlation analysis found that low expression of SMAD3 was influenced by hypermethylation on five CpG sites located at the promoter. Hypomethylation commonly occurs in SMAD3 in CRC patients. In conclusion, high frequency of hypomethylation of SMAD3 is commonly found in Western and Asian populations and potentially to be used for the early prediction of colorectal cancer.
Regarding breast cancer, finding new biomarkers is a promising strategy for lowering cancer mortality and incidence rates, which still ranks first among women worldwide. Chemotherapy sensitivity and resistance are responsible for treatment failure in more than 90% of breast cancer patients. This study aims to characterize the alteration pattern of thiosulfate sulfurtransferase-like domain containing 1 (TSTD1) in breast cancer patients and its applications, after utilizing the methylation level from The Cancer Genome Atlas (TCGA) dataset, we found that TSTD1 gene was hypomethylated and upregulated in breast cancer patients. Pairs of tissues from Taiwanese patients were analyzed, and we found that 68.25%, 65.09%, and 68.8% of patients exhibited TSTD1 mRNA overexpression, hypomethylation, and protein overexpression, respectively. Breast cancer patients who displayed overexpression of TSTD1 were substantially linked to poor chemotherapy outcomes and 5-year overall survival. In vitro data reveals that TSTD1 is involved in cell proliferation in MDA-MB-231 and T47D breast cancer cells. Compared with the control group, overexpression of TSTD1 in MCF7 breast cancer cells caused a significantly poor drug response to chemotherapy, specifically docetaxel and epirubicin. In a dose-dependent manner, the drug response of these cells to the tamoxifen treatment was significantly poor. Interestingly, hypomethylation ccfDNA of TSTD1 is related to the therapy progression in TNBC patients. In terms of a biological pathway, an increase in GSH/GSSG ratio and a decrease in ROS levels was found after TSTD1 knockdown, and TSTD1 may also act as an oncogene in lung cancer. In conclusion, promoter hypomethylation and overexpression of TSTD1 may serve as potential biomarkers for therapy responsiveness and poor 5-year survival in breast cancer patients. |
