Dataset Information

Elevated serum DAND5 is associated with metastasis and predicts poor prognosis in colorectal cancer.

ABSTRACT: The biologic and clinical significance of DAND5 remains unknown in colorectal cancer (CRC).Herein, we investigated the function of DAND5 and evaluated its clinical significance in both serum and matched primary tumors in patients with CRC.The role of DAND5 was explored in CRC cells and clinical significance of DAND5 was investigated in CRC patients (n = 217) and healthy controls (n = 63).Knockdown of DAND5 significantly decreased CRC cell proliferation, migration and invasion partly associated with epithelial-mesenchymal transition phenotype. Serum DAND5 levels in CRC were significantly higher than in normal controls and accurately distinguished CRC from healthy subjects. High serum DAND5 levels were significantly correlated with tumor differentiation, large tumor size, advanced Tumor Node Metastasis (TNM) stage, lymph node and liver metastasis, high carcinoembryonic antigen level, recurrence, poor overall and disease-free survival. Serum DAND5 level, together with lymph node metastasis, were independent prognostic factors for CRC patients. High DAND5 protein expression in CRC tissues was increased according to TNM stage. A significant positive correlation existed between serum DAND5 levels and matched DAND5 expression in CRC tissues.Our data provide novel evidence for the clinical significance of DAND5 as a potential biomarker for CRC prognosis.

SUBMITTER: Miao X

PROVIDER: S-EPMC5548344 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:PurposeMolecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.Patients and methodsThis study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan-Meier analysis with a log-rank test was used for the survival analysis.ResultsLAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer.ConclusionThese findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients.

Project description:BACKGROUND:In breast cancer, activation of bone morphogenetic protein (BMP) signaling and elevated levels of BMP-antagonists have been linked to tumor progression and metastasis. However, the simultaneous upregulation of BMPs and their antagonist, and the fact that both promote tumor aggressiveness seems contradictory and is not fully understood. METHODS:We analyzed the transcriptomes of the metastatic 66cl4 and the non-metastatic 67NR cell lines of the 4T1 mouse mammary tumor model to search for factors that promote metastasis. CRISPR/Cas9 gene editing was used for mechanistic studies in the same cell lines. Furthermore, we analyzed gene expression patterns in human breast cancer biopsies obtained from public datasets to evaluate co-expression and possible relations to clinical outcome. RESULTS:We found that mRNA levels of the BMP-antagonist Grem1, encoding gremlin1, and the ligand Bmp4 were both significantly upregulated in cells and primary tumors of 66cl4 compared to 67NR. Depletion of gremlin1 in 66cl4 could impair metastasis to the lungs in this model. Furthermore, we found that expression of Grem1 correlated with upregulation of several stem cell markers in 66cl4 cells compared to 67NR cells. Both in the mouse model and in patients, expression of GREM1 associated with extracellular matrix organization, and formation, biosynthesis and modification of collagen. Importantly, high expression of GREM1 predicted poor prognosis in estrogen receptor negative breast cancer patients. Analyses of large patient cohorts revealed that amplification of genes encoding BMP-antagonists and elevation of the corresponding transcripts is evident in biopsies from more than half of the patients and much more frequent for the secreted BMP-antagonists than the intracellular inhibitors of SMAD signaling. CONCLUSION:In conclusion, our results show that GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients. Gremlin1 could represent a novel target for therapy.

Dataset Information

Elevated serum DAND5 is associated with metastasis and predicts poor prognosis in colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets