Zhang N.-H.,Southern Medical University |
Li J.,Sun Yat Sen University |
Li Y.,Sun Yat Sen University |
Zhang X.-T.,Peking University |
And 5 more authors.
Experimental and Therapeutic Medicine | Year: 2012
Although CXCR4 and CD133 have been implicated in the metastatic process of malignant tumors, the clinicopathological significance of their expression in human colon cancer is not fully understood. The present study aimed to examine the expression of the CXCR4 and CD133 proteins in cases of stage II or III colon cancer and the related lymph nodes and to investigate the clinical and prognostic significance of these proteins in colon cancer. Immunohistochemical analysis was performed to examine CXCR4 and CD133 protein expression in paraffin-embedded stage II or III primary colon cancer tissues and matched lymph nodes. The correlation between the expression of the two proteins and clinicopathological parameters and the patient 5-year survival was analyzed. CXCR4 expression was detected in 74 of the 125 tumors (59.2%) and CD133 expression was detected in 45 (36.0%). The co-expression of CXCR4 and CD133 (both CXCR4 and CD133 were positive) was detected in 29 of the 125 tumors (23.2%). Compared with the other combinations, the co-expression of the CXCR4 and CD133 proteins was significantly associated with American Joint Committee on Cancer (AJCC) stage (P=0.029) and lymph node status (P=0.020). Log-rank analysis revealed that AJCC stage (P=0.014), lymph node status (P=0.011), CXCR4 expression (P=0.023), CD133 expression (P=0.034) and the co-expression of the CXCR4 and CD133 proteins (P=0.003) were significant prognostic indicators for the overall survival of patients. The results of the present study show that the co-expression of the CXCR4 and CD133 proteins is a risk factor for poor overall survival in stage II or III colon cancer patients, indicating that the co-expression of the CXCR4 and CD133 proteins contributes to the progression of colon cancer.
Deng Y.-J.,Southern Medical University |
Deng Y.-J.,Guangdong Provincial Key Laboratory of Molecular Tumour Pathology |
Tang N.,Southern Medical University |
Liu C.,Southern Medical University |
And 13 more authors.
Clinical Cancer Research | Year: 2014
Purpose: Cancer stem-like cells have been well accepted to be involved in recurrence and metastasis of cancers, but the prognostic potential of biomarkers integrating with metastasis and cancer stem-like cells for colorectal cancer is unclear. Experimental Design: We identified three proteins, CLIC4, ERp29, and Smac/DIABLO, from metastatic cancer stem-like cells of colorectal cancer and verified the proteins' role in metastatic behaviors. The proteins were detected by IHC in colorectal cancer tumors and matched colonic mucosa from patients with colorectal cancer who underwent radical surgery in the training cohort. The associations between proteins expression levels and five-year disease-specific survival (DSS) were evaluated to predict the survival probability in the training cohort of 421 cases and the validation cohort of 228 cases. Results: A three-protein panel including CLIC4, ERp29, and Smac/DIABLO, which was generated from multivariate analysis by excluding clinicopathologic characteristics from the training cohort, distinguished patients with colorectal cancer into very low-, low-, middle-, and high-risk groups with significant differences in five-year DSS probability (88.6%, 63.3%, 30.4%, 11.4%; P < 0.001). The panel is independent from tumor-node-metastasis staging system and histologic grading to predict prognosis, and also enables classification of validation cohort into four risk stratifications (five-year DSS probability is 98.2%, 80.2%, 25.6%, and 2.7%; P < 0.001). Conclusions: CLIC4, ERp29, and Smac/DIABLO integrated into a novel panel based on cancer stem-like cells in association with metastasis stratify the prognostic risks of colorectal cancer. Prediction of risks with molecular markers will benefit clinicians to make decisions of individual management with postoperative colorectal cancer patients. ©2014 AACR.
Li G.,Southern Medical University |
Liu C.,Southern Medical University |
Yuan J.,Southern Medical University |
Xiao X.,Southern Medical University |
And 8 more authors.
Clinical and Experimental Metastasis | Year: 2010
Single cell progenies (SCPs) inherit biological properties from their isogenetic mother cells. If a single cancer cell can give rise to progenies, which can be passaged sustainably in vitro and produce tumor in xenotransplantation, the cell should be cancer initiating cell. CD133 (Prominin-1, Prom1) is the marker of human colorectal cancer (CRC) stem cells and probably a marker of metastatic cancer stem cells (CSCs). Thirty-three SCPs of CRC cell line SW480 were isolated by limited dilution methods, thirty of which are CD133 positive and three negative. All of the CD133+ SCPs are tumorigenic, and the subcutaneous tumors expanded rapidly, while only 1 of 3 CD133- SCPs developed a minimal tumor in nude mice. Orthotopic transplantation experiments showed that CD133+ SCPs possessed heterogeneity in intestinal wall invasion, lymph node and liver metastases. CD133+ SCPs varied in cell growth, invasive ability, epithelial-mesenchymal-transition and expression of CSCs markers (CD133, CD44, and CXCR4) associated with metastatic potential. CD133- SCPs did not produce secondary transplanted tumor, intestinal invasion and metastasis. The results indicated CD133+ subpopulation of SW480 SCPs bear heterogeneous invasive and metastatic ability, and CRC-CSCs might be a heterogeous subpopulation. © 2010 Springer Science+Business Media B.V.
Hu Z.-Y.,Southern Medical University |
Hu Z.-Y.,Guangdong Provincial Key Laboratory of Molecular Tumour Pathology |
Liu Y.-P.,Southern Medical University |
Liu Y.-P.,Guangdong Provincial Key Laboratory of Molecular Tumour Pathology |
And 9 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2016
Our previous studies have shown that PRKA kinase anchor protein 9 (AKAP-9) is involved in colorectal cancer (CRC) cell proliferation and migration in vitro. However, whether or not AKAP-9 is important for CRC development or metastasis in vivo remains unknown. In the present study, we found that AKAP-9 expression was significantly higher in human colorectal cancer tissues than the paired normal tissues. In fact, AKAP-9 level correlated with the CRC infiltrating depth and metastasis. Moreover, the higher AKAP-9 expression was associated with the lower survival rate in patients. In cultured CRC cells, knockdown of AKAP-9 inhibited cell proliferation, invasion, and migration. AKAP-9 deficiency also attenuated CRC tumor growth and metastasis in vivo. Mechanistically, AKAP-9 interacted with cdc42 interacting protein 4 (CIP4) and regulated its expression. CIP4 levels were interrelated to the AKAP-9 level in CRC cells. Functionally, AKAP-9 was essential for TGF-β1-induced epithelial-mesenchymal transition of CRC cells, and CIP4 played a critical role in mediating the function of AKAP-9. Importantly, CIP4 expression was significantly up-regulated in human CRC tissues. Taken together, our results demonstrated that AKAP-9 facilitates CRC development and metastasis via regulating CIP4-mediated epithelial-mesenchymal transition of CRC cells. © 2016 Elsevier B.V.
Hao J.-M.,Southern Medical University |
Hao J.-M.,Guangdong Provincial Key Laboratory of Molecular Tumour Pathology |
Chen J.-Z.,Southern Medical University |
Chen J.-Z.,Guangdong Provincial Key Laboratory of Molecular Tumour Pathology |
And 10 more authors.
Journal of Pathology | Year: 2010
To understand the molecular mechanisms of metastasis and prognosis of colorectal cancer (CRC), we isolated single cell-derived progenies (SCPs) from SW480 cells in vitro and compared their metastatic potential in an orthotopic CRC tumour model in vivo. Two groups of SCPs with the capability of high and low metastasis, respectively, were obtained. By analysing the gene expression profiles of high (SCP51), low (SCP58) metastatic SCPs, and their parental cell line (SW480/EGFP), we demonstrated that 143 genes were differentially expressed either between SCP51 and SCP58 or between SCP58 and SW480/EGFP. Geneannotation enrichment analysis of DAVID revealed 80 genes in the top ten clusters of the analysis (gene enrichment score >1). Of the 80-gene set, 32 genes are potentially involved in metastasis, as revealed by Geneclip. Five putative metastatic genes (LYN, SDCBP, MAP4K4, DKK1, and MID1) were selected for further validations. Immunohistochemical analysis in a cohort of 181 CRC clinical samples showed that the individual expression of LYN, MAP4K4, and MID1, as well as the five-gene signature, was closely correlated with lymph node metastasis in CRC patients. More importantly, the individual expression of LYN, MAP4K4, SDCBP, and MID1, as well as the five-gene signature, was significantly correlated with overall survival in CRC patients. Thus, our five-gene signature may be able to predict metastasis and survival of CRC in the clinic, and opens new perspectives on the biology of CRC. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.