scholarly journals Elevated expression of AGGF1 predicts poor prognosis and promotes the metastasis of colorectal cancer

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.


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 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.


Chemotherapy ◽  
2022 ◽  
pp. 1-10
Author(s):  
Cheng Yang ◽  
Na Xie ◽  
Zhifei Luo ◽  
Xiling Ruan ◽  
Yixin Zhang ◽  
...  

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.


2017 ◽  
Vol 32 (2) ◽  
pp. 218-223 ◽  
Author(s):  
Xiangke Li ◽  
Feng Wang ◽  
Yan Sun ◽  
Qingxia Fan ◽  
Guangfei Cui

Background Long noncoding RNAs (lncRNAs) are emerging as key molecules in human cancer. In the present study, we explored the role of the lncRNA PANDAR in colorectal cancer (CRC). Methods The relative expression level of lncRNA PANDAR in CRC tissues and cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The associations between PANDAR expression and clinicopathological features of CRC patients were further analyzed. Kaplan-Meier survival analysis was performed to evaluate the value of PANDAR in the prognosis of CRC patients. Furthermore, the biological function of PANDAR on CRC cell growth, apoptosis and mobility was investigated through MTT, flow cytometry, transwell migration and invasion assays in vitro. Results The expression level of PANDAR was higher in CRC tissues and cells compared with adjacent nontumor tissues and normal colonic cell line NCM460. PANDAR expression was significantly correlated with local invasion, lymph node metastasis and TNM stage. Kaplan-Meier analysis showed that patients with high PANDAR expression had poorer overall survival than patients with low PANDAR expression. Multivariate Cox regression analysis indicated that PANDAR might be an independent prognostic factor for CRC patients. Furthermore, PANDAR knockdown significantly inhibited cell proliferation, cycle progression, migration and invasion of CRC in vitro. Conclusions Our results suggest that high expression of PANDAR was involved in CRC progression and could act as an independent biomarker for prognosis of CRC patients.


2017 ◽  
Vol 42 (1) ◽  
pp. 397-406 ◽  
Author(s):  
Qingguo Li ◽  
Yaqi Li ◽  
Junyan Xu ◽  
Sheng Wang ◽  
Ye Xu ◽  
...  

Background: Glycolysis is considered to be the root of cancer development and progression, which involved a multi-step enzymatic reaction. Our study aimed at figuring out which glycolysis enzyme participates in the development of colorectal cancer and its possible mechanisms. Methods: We firstly screened out Aldolase B (ALDOB) by performing qRT-PCR arrays of glycolysis-related genes in five paired liver metastasis and primary colorectal tissues, and further detected ALDOB protein with immunohistochemistry in tissue microarray (TMA) consisting of 229 samples from stage I-III colorectal cancer patients. CRISPR-Cas9 method was adopted to create knock out colon cancer cell lines (LoVo and SW480) of ALDOB. The effect of ALDOB on cell proliferation and metastasis was examined in vitro using colony formation assay as well as transwell migration and invasion assay, respectively. Results: In TMA, there was 64.6% of samples demonstrated strong intensity of ALDOB. High ALDOB expression were associated with poor overall survival and disease-free survival in both univariate and multivariate regression analyses (P<0.05). In vitro functional studies of CCK-8 demonstrated that silencing ALDOB expression significantly (P<0.05) inhibited proliferation, migration and invasion of colon cancer cells. Mechanically, silencing ALDOB activated epithelial markers and repressed mesenchymal markers, indicating inactivation of ALDOB may lead to inhibition of epithelial-mesenchymal transition (EMT). Conclusion: Upregulation of ALDOB promotes colorectal cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in colorectal cancer.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 443-443
Author(s):  
Akihiko Takeda

443 Background: Arm protein lost in epithelial cancers, on chromosome X (ALEX) is a novel subgroup within the armadillo family which has several ARM repeat domain. Our studies have revealed that overexpression of ALEX1 suppressed colony formation ability of stable human colorectal carcinoma cell lines. But clinical significance of ALEX1 expression in colorectal cancer patients is largely unknown. Methods: We examined the expression level of ALEX1 mRNA in matched tissue pairs of normal colorectal mucosa and colorectal tumor tissue by quantitative real-time RT-PCR Tumor specimens along with adjacent normal tissues were obtained from 49 patients with primary colorectal cancer undergoing complete surgical resection of tumors and lymph nodes, followed by adjuvant systemic therapy in some cases. All tissue samples were stored at -80°C until use. The 49 colorectal specimens comprised 26 well-differentiated and 23 moderately-differentiated adenocarcinoma. Corresponding extraneoplastic normal colon tissues from the same 49 patients were also examined. The pathological stages of the patients were as follows: stage I, 9 patients; stage II, 16 patients and stage III, 24 patients by pTNM classification. The post-surgical treatment observation period was from 277 to 3,631 days (1625.0 ± 1033.0 days). Results: In 34 cases out of 49 (69%) colorectal tumor tissues, greater than a 50% reduction of the ALEX1 mRNA level was observed in comparison to adjacent normal mucosa tissues. ALEX1 mRNA was significantly reduced in colorectal tumor tissues than those in normal mucosa (p=0.01459, Mann–Whitney U-test). The 17 cases with higher ALEX1 gene expression (tumor/normal value ³a0.20) significantly revealed a better disease-free survival rate than the other 32 cases (< 0.20; p = 0.045, log-rank test), which showed significant correlations between ALEX1 expression and better prognosis. There was no significant relationship between ALEX1 expression and the other clinicopathological features. Conclusions: Our findings may support that ALEX1 functions as a tumor suppressor in colorectal cancer progression. Examination of ALEX1 expression might be helpful for predicting the prognosis of patients with curative resected colorectal cancer.


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.


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