scholarly journals High MEIS3 expression intimates poor prognosis for clinical stage II/III colorectal cancer patients

Author(s):  
Ma Jian ◽  
Haitao Li ◽  
Meihua Wang ◽  
Jian Chen ◽  
Ming Zhu ◽  
...  

Abstract Background The middle stages colorectal cancer (CRC) patients are severely differentiated, so suitable biomarkers are required to distinguish the cohort with high recurrence risk. We hypothesized that among the specimens retained after surgery, those from cohort who relapsed quickly after surgery may be more capable to find the high-risk markers. Methods A lable-free analysis was employed to identify candidate proteins markers in CRC tissues relapsed within three years since surgery. Combined with MEIS3 immunohistochemistry characteristic, we analyzed MEIS3 (myeloid ecotropic viral insertion site 3) expression level in clinical stages. Kaplan-Meier Analysis was adopted to analyze the correlation between gene expression and 5-year disease-free survival (DFS) of CRC patients. Finally, cell biology methods were employed to analyze molecular mechanism for tumor cell migration and metastasis. Results Through proteomics immunohistochemistry analysis, we identified protein MEIS3 are mainly located in growth front and other highly invasive areas in cancer. And its expression level is closely associated to the clinical stage of CRC. Furthermore, high MEIS3 expression in cancer tissues is closely related to the 5-year DFS expectations of CRC patients. The 5-year DFS of stage II patients with high MEIS3 expression was significantly lower than that of low MEIS3 expression (60.2% % vs 81.1% p < 0.01). The 5-year DFS III patients with high MEIS3 expression was also significantly lower than those of low MEIS3 expression (38.1% vs 56.7% p < 0.01). The analysis on SW480 cells showed that MEIS3 may promote migration and invasion of CRC cells by regulating the expression of LAMB1. Conclusion This study intimates that MEIS3 overexpression is associated to poor prognosis for stage II and III patients, and MEIS3 can promote the CRC cells invasion through regulating LAMB1 expression.

2021 ◽  
Author(s):  
Ma Jian ◽  
Haitao Li ◽  
Meihua Wang ◽  
Ming Zhu ◽  
Ang Li ◽  
...  

Abstract Background The middle stages colorectal cancer (CRC) patients are severely differentiated, so suitable biomarkers are required to distinguish the cohort with high recurrence risk. We hypothesized that among the specimens retained after surgery, those from cohort who relapsed quickly after surgery may be more capable to find the high-risk markers. Methods A lable-free analysis was employed to identify candidate proteins markers in CRC tissues relapsed within three years since surgery. Combined with MEIS3 immunohistochemistry characteristic, we analyzed MEIS3 (myeloid ecotropic viral insertion site 3) expression level in clinical stages. Kaplan-Meier Analysis was adopted to analyze the correlation between gene expression and 5-year disease-free survival (DFS) of CRC patients. Finally, cell biology methods were employed to analyze molecular mechanism for tumor cell migration and metastasis. Results Through proteomics immunohistochemistry analysis, we identified protein MEIS3 are mainly located in growth front and other highly invasive areas in cancer. And its expression level is closely associated to the clinical stage of CRC. Furthermore, high MEIS3 expression in cancer tissues is closely related to the 5-year DFS expectations of CRC patients. The 5-year DFS of stage II patients with high MEIS3 expression was significantly lower than that of low MEIS3 expression (60.2% % vs 81.1% p < 0.01). The 5-year DFS III patients with high MEIS3 expression was also significantly lower than those of low MEIS3 expression (38.1% vs 56.7% p < 0.01). The analysis on SW480 cells showed that MEIS3 may promote migration and invasion of CRC cells by regulating the expression of LAMB1. Conclusion This study intimates that MEIS3 overexpression is associated to poor prognosis for stage II and III patients, and MEIS3 can promote the CRC cells invasion through regulating LAMB1 expression.


2019 ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He

Abstract Background: Angiogenic factor with G-patch and FHA domains 1 (AGGF1) can promote angiogenesis and increasing evidence has highlighted the important roles of AGGF1 in tumorigenesis. However, the differential expression as well as the biological functions of AGGF1 in colorectal cancer (CRC) remain to be established. The purpose of the present study is therefore to identify the effect of AGGF1 on prognosis and metastasis in CRC patients. Methods: The expression level of AGGF1 in CRC was examined by qPCR, western blot and immunohistochemistry in a tissue microarray containing 236 CRC specimens and paired normal mucosae. And the effect of AGGF1 on CRC cell malignance was investigated in our established stable AGGF1 upregulated and knockdown CRC cell lines. Results: The expression level of AGGF1 in CRC tissue was not significantly different to that in adjacent normal mucosa at the mRNA level. However, at the protein level, AGGF1 expression in CRC tissues was significantly higher than in paired normal mucosa, which showed a clear association with TNM stage, AJCC stage, vascular invasion, and differentiation. Further, we revealed an apparent correlation between AGGF1 expression and poorer disease-free survival and overall survival of CRC patients. In addition, we discovered that AGGF1 significantly promoted CRC cell wound healing, migration, and invasion in vitro and distant metastasis in vivo. Conclusions: Our study demonstrates the aberrant overexpression of AGGF1 in CRC and provides a basis on which to explore the application of AGGF1 as a potential therapeutic target for CRC patients, especially for CRC patients with distant metastasis.


2019 ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He

Abstract Abstract Background: Angiogenic factor with G-patch and FHA domains 1 (AGGF1) can promote angiogenesis and increasing evidence has highlighted the important roles of AGGF1 in tumorigenesis. However, the expression patterns as well as the biological functions of AGGF1 in colorectal cancer (CRC) remain to be established. The purpose of the present study is therefore to identify the effect of AGGF1 on prognosis and metastasis in CRC patients. Methods: The expression level of AGGF1 in CRC was examined by qPCR, western blot and immunohistochemistry in a tissue microarray containing 101 CRC specimens. And the effect of AGGF1 on CRC cell malignance was investigated in our established stable AGGF1 upregulated and knockdown CRC cell lines. Results: The expression level of AGGF1 in CRC tissue was not significantly different to that in adjacent normal mucosa at the mRNA level. However, at the protein level, AGGF1 expression in CRC tissues was significantly higher than in paired normal mucosa, which showed a clear association with TNM stage, AJCC stage, vascular invasion, and differentiation. Further, we revealed an apparent correlation between AGGF1 expression and poorer disease-free survival and overall survival of CRC patients. In addition, we discovered that AGGF1 significantly promoted CRC cell wound healing, migration, and invasion in vitro and distant metastasis in vivo . Conclusions: Our study demonstrates the aberrant expression of AGGF1 in CRC and provides a basis on which to explore the application of AGGF1 as a novel prognostic biomarker for CRC patients, especially for CRC patients with distant metastasis.


2019 ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He

Abstract Abstract Background: Angiogenic factor with G-patch and FHA domains 1 (AGGF1) can promote angiogenesis and increasing evidence has highlighted the important roles of AGGF1 in tumorigenesis. However, the expression patterns as well as the biological functions of AGGF1 in colorectal cancer (CRC) remain to be established. The purpose of the present study is therefore to identify the effect of AGGF1 on prognosis and metastasis in CRC patients. Methods: The expression level of AGGF1 in CRC was examined by qPCR, western blot and immunohistochemistry in a tissue microarray containing 101 CRC specimens. And the effect of AGGF1 on CRC cell malignance was investigated in our established stable AGGF1 upregulated and knockdown CRC cell lines. Results: The expression level of AGGF1 in CRC tissue was not significantly different to that in adjacent normal mucosa at the mRNA level. However, at the protein level, AGGF1 expression in CRC tissues was significantly higher than in paired normal mucosa, which showed a clear association with TNM stage, AJCC stage, vascular invasion, and differentiation. Further, we revealed an apparent correlation between AGGF1 expression and poorer disease-free survival and overall survival of CRC patients. In addition, we discovered that AGGF1 significantly promoted CRC cell wound healing, migration, and invasion in vitro and distant metastasis in vivo . Conclusions: Our study demonstrates the aberrant expression of AGGF1 in CRC and provides a basis on which to explore the application of AGGF1 as a novel prognostic biomarker for CRC patients, especially for CRC patients with distant metastasis.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He

Abstract Background Angiogenic factor with G-patch and FHA domains 1 (AGGF1) can promote angiogenesis and increasing evidence has highlighted the important roles of AGGF1 in tumorigenesis. However, the differential expression as well as the biological functions of AGGF1 in colorectal cancer (CRC) remain to be established. The purpose of the present study is therefore to identify the effect of AGGF1 on prognosis and metastasis in CRC patients. Methods The expression level of AGGF1 in CRC was examined by qPCR, western blot and immunohistochemistry in a tissue microarray containing 236 CRC specimens and paired normal mucosae. And the effect of AGGF1 on CRC cell malignance was investigated in our established stable AGGF1 upregulated and knockdown CRC cell lines. Results The expression level of AGGF1 in CRC tissue was not significantly different to that in adjacent normal mucosa at the mRNA level. However, at the protein level, AGGF1 expression in CRC tissues was significantly higher than in paired normal mucosa, which showed a clear association with TNM stage, AJCC stage, vascular invasion, and differentiation. Further, we revealed an apparent correlation between AGGF1 expression and poorer disease-free survival and overall survival of CRC patients. In addition, we discovered that AGGF1 significantly promoted CRC cell wound healing, migration, and invasion in vitro and distant metastasis in vivo. Conclusions Our study demonstrates the aberrant overexpression of AGGF1 in CRC and provides a basis on which to explore the application of AGGF1 as a potential therapeutic target for CRC patients, especially for CRC patients with distant metastasis.


2019 ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He

Abstract Background: Angiogenic factor with G-patch and FHA domains 1 (AGGF1) can promote angiogenesis and increasing evidence has highlighted the important roles of AGGF1 in tumorigenesis. However, the differential expression as well as the biological functions of AGGF1 in colorectal cancer (CRC) remain to be established. The purpose of the present study is therefore to identify the effect of AGGF1 on prognosis and metastasis in CRC patients. Methods: The expression level of AGGF1 in CRC was examined by qPCR, western blot and immunohistochemistry in a tissue microarray containing 101 CRC specimens and paired normal mucosae. And the effect of AGGF1 on CRC cell malignance was investigated in our established stable AGGF1 upregulated and knockdown CRC cell lines. Results: The expression level of AGGF1 in CRC tissue was not significantly different to that in adjacent normal mucosa at the mRNA level. However, at the protein level, AGGF1 expression in CRC tissues was significantly higher than in paired normal mucosa, which showed a clear association with TNM stage, AJCC stage, vascular invasion, and differentiation. Further, we revealed an apparent correlation between AGGF1 expression and poorer disease-free survival and overall survival of CRC patients. In addition, we discovered that AGGF1 significantly promoted CRC cell wound healing, migration, and invasion in vitro and distant metastasis in vivo. Conclusions: Our study demonstrates the aberrant expression of AGGF1 in CRC and provides a basis on which to explore the application of AGGF1 as a novel prognostic biomarker as well as a therapeutic target for CRC patients, especially for CRC patients with distant metastasis.


2019 ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He

Abstract Background: Angiogenic factor with G-patch and FHA domains 1 ( AGGF1 ) can promote angiogenesis and increasing evidence has highlighted the important roles of AGGF1 in tumorigenesis. However, the differential expression as well as the biological functions of AGGF1 in colorectal cancer ( CRC ) remain to be established. The purpose of the present study is therefore to identify the effect of AGGF1 on prognosis and metastasis in CRC patients. Methods: The expression level of AGGF1 in CRC was examined by qPCR, western blot and immunohistochemistry in a tissue microarray containing 236 CRC specimens and paired normal mucosae. And the effect of AGGF1 on CRC cell malignance was investigated in our established stable AGGF1 upregulated and knockdown CRC cell lines. Results: The expression level of AGGF1 in CRC tissue was not significantly different to that in adjacent normal mucosa at the mRNA level. However, at the protein level, AGGF1 expression in CRC tissues was significantly higher than in paired normal mucosa, which showed a clear association with TNM stage, AJCC stage, vascular invasion, and differentiation. Further, we revealed an apparent correlation between AGGF1 expression and poorer disease-free survival and overall survival of CRC patients. In addition, we discovered that AGGF1 significantly promoted CRC cell wound healing, migration, and invasion in vitro and distant metastasis in vivo . Conclusions: Our study demonstrates the aberrant overexpression of AGGF1 in CRC and provides a basis on which to explore the application of AGGF1 as a potential therapeutic target for CRC patients, especially for CRC patients with distant metastasis.


2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.


2005 ◽  
Vol 91 (2) ◽  
pp. 168-172 ◽  
Author(s):  
Mahmut Gumus ◽  
Perran Fulden Yumuk ◽  
Gul Atalay ◽  
Mehmet Aliustaoglu ◽  
Beyza Macunluoglu ◽  
...  

Background Regional lymph node (LN) involvement in colorectal cancer (CRC) identifies the stage and the subset of patients who would benefit from adjuvant chemotherapy. We performed a retrospective analysis to determine if the number of recovered LNs was associated with long-term outcome in patients operated on for stage II and III CRC. Patients and methods Hospital records of 179 patients with CRC followed in our unit from 1997 to April 2003 were reviewed. Results On average 11.68 ± 7.3 LNs were sampled per surgical specimen. Sampling of at least nine LNs appeared to be the minimum number required for accurately predicting LN involvement ( P = 0.002). Three-year rates of disease-free survival (DFS), local recurrence-free survival (LRFS) and overall survival (OS) were lower in patients with fewer than nine LNs sampled ( P = 0.032, P = 0.006 and P = 0.04, respectively). However, this had no impact on the three-year distant metastasis-free survival rate (DMFS) ( P = 0.472). In stage II disease, patients with nine or more LNs dissected had significantly higher three year DFS and LRFS rates than the subgroup with fewer than nine LNs dissected ( P = 0.024 and P = 0.015, respectively), but this did not have any effect on DMFS or OS ( P = 0.406 and P = 0.353, respectively). Conclusion Current protocols provide adjuvant treatment in stage III patients; the problem is to correctly determine stage by recovering as many LNs as possible.


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