Project description:We performed RNAseq analysis of metastatic colorectal cancer from 16 patients. Normal adjacent tissue, primary tissue, and metastatic tissue were analyzed to uncover metastatic progression and difference between primary and distant metastatic lesions.
Project description:In this study, we conducted a microarray-based analysis to identify differentially expressed miRNAs in CRC by comparing miRNA profiles among primary CRC tissues from patients with liver metastases, primary tissues without liver metastases, and liver metastatic lesions. microRNAs (miRNAs) have been shown to have a potential for cancer diagnosis lately. The main objective of this study is to identify a novel biomarker serum miRNA from the patients with colorectal cancer (CRC). Microarray analysis of miRNA expression was performed using paired pre- and post- operative serum from 10 CRC patients. Two miRNAs (let-7a, miR-199a-3p) decreased significantly in the post-operative serum when compared to pre-operative serum (P=0.015 and 0.029, respectively). Microarrays were performed for the testing cohort of primary CRC lesions (n=28) and liver metastatic lesions (n=8).
Project description:The patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received bevacizumab therapy as first line or second line treatment. Responders and nonresponders were determined based on RECIST and confirmed by CT or MRI. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. Colorectal cancer patients who had undergone surgical resection of colorectal cancer were studied. To identify molecular signatures to predict response to bevacizumab, gene expression profiles were compared between Reponder and Non-responder.
Project description:The patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received modified FOLFOX6. Responders and nonresponders were determined based on the best observed response at the end of the first-line treatment, mFOLFOX6. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. Colorectal cancer patients who had undergone surgical resection of colorectal cancer were studied. To identify molecular signatures to predict response to mFOLFOX6 regimen, gene expression profiles were compared between Reponder and Non-responder. Some patients are overlapped with Bevacizumab therapy.
Project description:<p>BRCA1 mutations are a hallmark of hereditary ovarian cancer, strongly linked to deficiencies in homologous recombination (HR) DNA repair and impaired DNA replication fork protection. However, its roles in cancer progression beyond maintaining genomic integrity remain poorly understood. Through metabolomics approaches, we found BRCA1-deficiency strikingly increased choline metabolism. Loss of BRCA1 promotes choline uptake through upregulating choline transporter-like protein 4 (CTL4). BRCA1 directly binds and recruits EZH2-mediated H3K27Me3 deposition to CTL4 promoter. CTL4 was therefore overexpressed in ovarian cancer tissues with BRCA1 mutations. Furthermore, BRCA1-deficiency significantly promotes ovarian cancer invasion, while inhibition of CTL4 reverses the high metastatic potential of BRCA1-deficient ovarian cancer cells, suggesting the functionality and specificity of CTL4 as a therapeutic target. Additionally, we discovered that phosphocholine, the choline metabolite increased by CTL4 overexpression, interacted with and stabilized the epithelial-to-mesenchymal transition inducer FAM3C in BRCA1-deficient ovarian cancer cells. Importantly, we identified a potent CTL4 inhibitor, DT-13, which significantly reduces choline metabolism and effectively suppresses metastasis in BRCA1-deficient ovarian cancers. Therefore, our study uncovers a mechanism underlying metastasis in BRCA1-deficient cancers and identifies CTL4 as a therapeutic target for metastatic ovarian cancer patients with BRCA1 mutations.</p>
Project description:Colorectal cancer (CRC) is a commonly occurring cancer worldwide. Metastasis and recurrence are the major causes of cancer-related death. CRC progression is a multistep process, and extensive efforts have been made to identify the genomic and transcriptomic alterations that occur during this process. However, whether primary tumors and metastatic lesions possess distinct biological features remains unclear. We established 74 patient-derived organoids (PDOs) from primary tumors and patient-matched metastatic and recurrent lesions.