Zhangjiang Center for Translational Medicine

Shanghai, China

Zhangjiang Center for Translational Medicine

Shanghai, China

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Cheng H.,Fudan University | Liu C.,Fudan University | Jiang J.,Fudan University | Luo G.,Fudan University | And 8 more authors.
International Journal of Cancer | Year: 2017

Cell-free circulating tumor DNA (ctDNA) in plasma has been used as a potential noninvasive biomarker for various tumors. Our study was performed to evaluate the clinical implications of ctDNA detection in patients with metastatic pancreatic cancer. First, we attempted to prospectively screen a panel of 60 genes in cell-free DNA (cfDNA) from ten metastatic pancreatic cancer patients via exome sequencing. Second, droplet digital PCR (ddPCR) was used to identify potential mutations in a cohort of 188 patients with metastatic pancreatic cancer. Finally, to preliminary evaluate the potential role of ctDNA in monitoring tumor responses following chemotherapy, we detected the presence of ctDNA in serial plasma samples from 13 metastatic pancreatic cancer patients (Clinical trial: NCT02017015). The analysis revealed five somatic mutations at BRCA2, EGFR, KDR and ERBB2 gene loci. The frequencies of ctDNA mutation at BRCA2, KDR, EGFR, ERBB2 exon17 and ERBB2 exon27 were 11.7%, 13.8%, 13.3%, 13.3% and 6.4% respectively. Univariate and multivariate analyses identified the ERBB2 exon17 mutation (p = 0.035, HR = 1.61) as an independent factor associated with overall survival among metastatic pancreatic cancer patients. Furthermore, the rate of coincident detection of ctDNA and response to treatment as assessed by CT imaging was 76.9% (10 of 13 cases), and the presence of ctDNA provided the earliest measure of treatment in 6 of 10 patients (60%). ctDNA sequencing may have clinical value for determining metastatic pancreatic cancer treatment and monitoring the tumor response. © 2017 UICC


Wu W.,Xi'an Jiaotong University | Zhang Z.,Zhangjiang Center for Translational Medicine | Gao X.H.,Shanghai University | Shen Z.,Xi'an Jiaotong University | And 10 more authors.
Oncotarget | Year: 2017

Circulating tumor cells (CTC) are useful in early detection of colorectal cancer. This study described a newly developed platform, integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH), to assess CTCs in colorectal cancer. CTCs were detected by SE-iFISH in 40 of 44 preoperative colorectal cancer patients, and yielded a sensitivity of 90.9%, which was significantly higher than CellSearch system (90.9% vs. 43.2%, P=0.033). No significant association was found between tumor stage, survival and preoperative CTC number. CTCs were detected in 10 colorectal cancer patients one week after surgery; seven patients with decreased CTC numbers (compared with preoperative CTC number) were free of recurrence; whereas two of the three patients with increased CTC numbers had tumor recurrence. Moreover, CTCs were detected in 34 colorectal cancer patients three months after surgery; patients with CTC < 2 at three months after surgery had significantly longer Progression Free Survival than those with CTC > =2 (P=0.019); patients with decreased CTC number (compared with preoperative CTC number) had significantly longer Progression Free Survival than those with increased CTC number (P=0.003). In conclusion, CTCs could be detected in various stages of colorectal cancer using SE-iFISH. Dynamic monitoring of CTC numbers could predict recurrence and prognosis.


Chen G.,Fudan University | Shi T.,East China Normal University | Shi L.,Fudan University | Shi L.,Fudan Zhangjiang Center for Clinical Genomics | Shi L.,Zhangjiang Center for Translational Medicine
Science China Life Sciences | Year: 2016

Bioinformatics methods for various RNA-seq data analyses are in fast evolution with the improvement of sequencing technologies. However, many challenges still exist in how to efficiently process the RNA-seq data to obtain accurate and comprehensive results. Here we reviewed the strategies for improving diverse transcriptomic studies and the annotation of genetic variants based on RNA-seq data. Mapping RNA-seq reads to the genome and transcriptome represent two distinct methods for quantifying the expression of genes/transcripts. Besides the known genes annotated in current databases, many novel genes/transcripts (especially those long noncoding RNAs) still can be identified on the reference genome using RNA-seq. Moreover, owing to the incompleteness of current reference genomes, some novel genes are missing from them. Genome- guided and de novo transcriptome reconstruction are two effective and complementary strategies for identifying those novel genes/transcripts on or beyond the reference genome. In addition, integrating the genes of distinct databases to conduct transcriptomics and genetics studies can improve the results of corresponding analyses. © 2016 The Author(s)


Li S.,Xi'an Jiaotong University | Wang L.,Xi'an Jiaotong University | Ma Z.,Xi'an Jiaotong University | Ma Y.,Xi'an Jiaotong University | And 3 more authors.
Oncology Letters | Year: 2015

Lung cancer is the leading cause of cancer‑related mortality worldwide. The majority of lung cancers are sporadic, and familial cases are extremely rare. Previous studies have mainly focused on sporadic lung cancer and identified a large quantity of driver genes. However, familial lung cancers are rarer and studied less. The present study recruited a Chinese family in which multiple members had developed lung squamous carcinoma. To find the causative mutations, whole exome sequencing was conducted using a peripheral blood sample of one lung squamous carcinoma patient, and certain variants were validated in more samples. Whole exome sequencing analysis obtained ~2.0 Gb of data (an average of 60x depth for each targeted base), and further validation experiments identified two functional variants in two cancer‑related genes (c.1218delA:p.E406fs in PDE4DIP and C1342A:p.L448I in CLTCL1). This study therefore provides useful sources for the further study of hereditary lung cancer. © 2015, Spandidos Publications. All rights reserved.


He Q.,Jinan Military General Hospital of PLA | Peng B.,Zhangjiang Center for Translational Medicine | Zhuang D.,Jinan Military General Hospital of PLA | Xiao L.,Jinan Military General Hospital of PLA | And 11 more authors.
Cancer Biomarkers | Year: 2015

BACKGROUND: The molecular classification of breast cancer mainly focuses on estrogen receptor (ER), Progesterone receptor (PgR), and Human Epidermal Growth Factor Receptor 2(HER2/Neu) status detected by immunohistochemistry (IHC) analysis. The β -tubulin isotype III (TUBB3) gene was thought to be a marker of taxane resistance or cancer aggressiveness. METHODS: To evaluate the clinicopathological significance of TUBB3 expression in breast cancer patients, we measured TUBB3 mRNA levels in 92 breast cancer patients by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and examined their correlation with ER, PgR, and HER2 status detected by IHC. RESULTS: We observed a significant positive correlation between the TUBB3 mRNA expression and the immunohistochemical positivity of both PgR (p 0.000) and HER2 (p 0.001). In addition, TUBB3 mRNA expression was associated with lymph nodes status (P 0.008) and tumor stages (0.029), but no correlation was found with other clinicopathological features, such as age, pathohistological grades and tumor size. CONCLUSIONS: In conclusion, TUBB3 expression correlated significantly with molecular markers of breast cancer, such as PgR and HER2, suggesting that TUBB3 mRNA level facilitate the identification of a subset of patients who respond to Taxane treatment in addition to hormonal therapy and trastuzumab. © 2015 - IOS Press and the authors. All rights reserved.


Gao S.,Henan Key Laboratory of Cancer Epigenetic | Zhou F.,Anyang Peoples Hospital | Zhao C.,Fudan Zhangjiang Center for Clinical Genomics | Ma Z.,Henan Key Laboratory of Cancer Epigenetic | And 11 more authors.
Tumor Biology | Year: 2016

Gastric cardia adenocarcinoma (GCA), which occurs at the gastroesophageal boundary, is one of the most malignant types of cancer. Over the past 30 years, the incidence of GCA has increased by approximately sevenfold, which has a more substantial increase than that of many other malignancies. However, as previous studies mainly focus on non-cardia gastric cancer, until now, the mechanisms behind GCA remain largely unknown. MicroRNAs (miRNAs) have been shown to play pivotal roles in carcinogenesis. To gain insight into the molecular mechanisms regulated by miRNAs in GCA development, we investigated miRNA expression profiles using 81 pairs of primary GCAs and corresponding non-tumorigenic tissues. First, 21 pairs of samples were used for microarray analysis, and then another 60 pairs of samples were used for further analysis. Our results showed that 464 miRNAs (237 upregulated, 227 downregulated, false discovery rate FDR <0.05) were differently expressed between GCA and non-tumor tissues. Pearson test and pathway analysis revealed that these dysregulated miRNA correlated coding RNAs may have effects on several cancer-related pathways. Four miRNAs (miR-1244, miR-135b-5p, miR-3196, and miR-628-3p) were found to be associated with GCA differentiation. One miRNA, miR-196a-5p, was found to be associated with age of GCA onset. Further, survival analysis showed that the expression level of miR-135b-5p was associated with GCA survival. Taken together, our study first provided the genome-wide expression profiles of miRNA in GCA and will be good help for further functional studies. © 2016 International Society of Oncology and BioMarkers (ISOBM)


Jiang H.,Shandong University | Wang J.,Shandong University | Yuan D.F.,Zhengzhou University | Fang J.W.,Weifang Traditional Chinese Hospital | Li Z.,Zhangjiang Center for Translational Medicine
Indian Journal of Cancer | Year: 2014

Objective: The aim was to evaluate the feasibility and safety of early chest tube removal after complete video-assisted thoracic lobectomy (CVATL). Methods: Retrospective analysis was performed on effects of chest tube removal on patients with lung cancer after pulmonary lobectomy between November 2013 and October 2014. 154 eligible patients included 97 cases for CVATL and 57 cases for open thoracic lobectomy. Patients with CVATL were divided randomly into experimental group (EG) and control group (CG), in which 51 patients in EG had chest tube removal on the 2 nd day after operation; 46 patients in CG had the tube removal when the drainage volume <100 ml/day. Patients in open thoracic lobectomy group (OG) had the tubes removal as CG. The drainage volumes of the 1 st and 2 nd 24 h after operation, duration of chest tubes, cases of pain alleviation, and recurrent pleural effusions requiring reintervention were measured. Results: The average drainage volume of the 1 st 24 h after operation of CVATL group from EG and CG was significantly reduced than that in OG (260.41 ml vs. 353.16 ml, P < 0.001). The average drainage volume of the 2 nd 24 h after operation of CG was significantly reduced than that in OG (163.91 ml vs. 222.98 ml, P < 0.001). The average duration of chest tube of CG for 2.98 days showed significant different compared with OG for 3.81 days (P < 0.001). Chest tube removal in CVATL group increased more chest pain alleviation than OG (80.4% vs. 56.1%, P = 0.001). The frequencies of recurrent pleural effusions requiring reintervention were 5.88% (3/51), 4.35% (2/46) and 5.26% (3/57), respectively, which had no significant differences between three groups (P = 1.000). Conclusions: Complete video-assisted thoracic lobectomy brings less drainage volume after operation. Early removal of chest tube in CVATL shows feasible and safe and demonstrates that it may reduce postoperative pain and help fast recovery.


PubMed | Zhangjiang Center for Translational Medicine and Jinan Military General Hospital of PLA
Type: Journal Article | Journal: Cancer biomarkers : section A of Disease markers | Year: 2015

The molecular classification of breast cancer mainly focuses on estrogen receptor (ER), Progesterone receptor (PgR), and Human Epidermal Growth Factor Receptor 2(HER2/Neu) status detected by immunohistochemistry (IHC) analysis. The -tubulin isotype III (TUBB3) gene was thought to be a marker of taxane resistance or cancer aggressiveness.To evaluate the clinicopathological significance of TUBB3 expression in breast cancer patients, we measured TUBB3 mRNA levels in 92 breast cancer patients by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and examined their correlation with ER, PgR, and HER2 status detected by IHC.We observed a significant positive correlation between the TUBB3 mRNA expression and the immunohistochemical positivity of both PgR (p= 0.000) and HER2 (p= 0.001). In addition, TUBB3 mRNA expression was associated with lymph nodes status (P= 0.008) and tumor stages (0.029), but no correlation was found with other clinicopathological features, such as age, pathohistological grades and tumor size.In conclusion, TUBB3 expression correlated significantly with molecular markers of breast cancer, such as PgR and HER2, suggesting that TUBB3 mRNA level facilitate the identification of a subset of patients who respond to Taxane treatment in addition to hormonal therapy and trastuzumab.


PubMed | Zhangjiang Center for Translational Medicine and Xi'an Jiaotong University
Type: Journal Article | Journal: Oncology letters | Year: 2015

Lung cancer is the leading cause of cancer-related mortality worldwide. The majority of lung cancers are sporadic, and familial cases are extremely rare. Previous studies have mainly focused on sporadic lung cancer and identified a large quantity of driver genes. However, familial lung cancers are rarer and studied less. The present study recruited a Chinese family in which multiple members had developed lung squamous carcinoma. To find the causative mutations, whole exome sequencing was conducted using a peripheral blood sample of one lung squamous carcinoma patient, and certain variants were validated in more samples. Whole exome sequencing analysis obtained ~2.0 Gb of data (an average of 60x depth for each targeted base), and further validation experiments identified two functional variants in two cancer-related genes (c.1218delA:p.E406fs in PDE4DIP and C1342A:p.L448I in CLTCL1). This study therefore provides useful sources for the further study of hereditary lung cancer.


PubMed | Henan University of Science and Technology, Zhangjiang Center for Translational Medicine, Fudan Zhangjiang Center for Clinical Genomics and Anyang Peoples Hospital
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

Gastric cardia adenocarcinoma (GCA), which occurs at the gastroesophageal boundary, is one of the most malignant types of cancer. Over the past 30years, the incidence of GCA has increased by approximately sevenfold, which has a more substantial increase than that of many other malignancies. However, as previous studies mainly focus on non-cardia gastric cancer, until now, the mechanisms behind GCA remain largely unknown. MicroRNAs (miRNAs) have been shown to play pivotal roles in carcinogenesis. To gain insight into the molecular mechanisms regulated by miRNAs in GCA development, we investigated miRNA expression profiles using 81 pairs of primary GCAs and corresponding non-tumorigenic tissues. First, 21 pairs of samples were used for microarray analysis, and then another 60 pairs of samples were used for further analysis. Our results showed that 464 miRNAs (237 upregulated, 227 downregulated, false discovery rate FDR <0.05) were differently expressed between GCA and non-tumor tissues. Pearson test and pathway analysis revealed that these dysregulated miRNA correlated coding RNAs may have effects on several cancer-related pathways. Four miRNAs (miR-1244, miR-135b-5p, miR-3196, and miR-628-3p) were found to be associated with GCA differentiation. One miRNA, miR-196a-5p, was found to be associated with age of GCA onset. Further, survival analysis showed that the expression level of miR-135b-5p was associated with GCA survival. Taken together, our study first provided the genome-wide expression profiles of miRNA in GCA and will be good help for further functional studies.

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