Evaluation of Hepatic-Metastasis Risk of Colorectal Cancer upon the Protein Signature of PI3K/AKT Pathway

2008 ◽  
Vol 7 (8) ◽  
pp. 3507-3515 ◽  
Author(s):  
Bin Kang ◽  
Chunyi Hao ◽  
Hongyi Wang ◽  
Jun Zhang ◽  
Rui Xing ◽  
...  
2007 ◽  
Vol 23 (6) ◽  
pp. 477
Author(s):  
Sang Chul Yun ◽  
Hyung Chul Kim ◽  
Chong Woo Chu ◽  
Eung Jin Shin ◽  
Moo Jun Baek ◽  
...  

2021 ◽  
Author(s):  
Zhewen Zheng ◽  
Xue Zhang ◽  
Jian Bai ◽  
Long Long ◽  
Di Liu ◽  
...  

Abstract BackgroundPhosphoglucomutase 1(PGM1) is known for its involvement in cancer pathogenesis. However, its biological role in colorectal cancer (CRC) is unknown. Here, we studied the functions and mechanisms of PGM1 in CRC.Methods We verified PGM-1 as a DEG by a comprehensive strategy of the TCGA-COAD dataset mining and computational biology. Relative levels of PGM-1 in CRC tumors and adjoining peritumoral tissue were identified by qRT-PCR, WB, and IHC staining in a tissue microarray. PGM1 functions were analyzed using CCK8, EdU, colony formation, cell cycle, apoptosis, and Transwell migration and invasion assays. The influence of PGM1 was further investigated using tumor formation in vivo.ResultsPGM1 mRNA and protein were both reduced in CRC and the reduction was related to CRC pathology and overall survival. PGM1 knockdown stimulated both proliferation and colony formation, promoting cell cycle arrest and apoptosis while overexpression has opposite effects in CRC cells both in vivo and in vitro. Furthermore, we lined the actions of PGM1 to the PI3K/ AKT pathway. ConclusionWe verified that PGM1 suppresses CRC through the PI3K/ AKT pathway. These results suggest the potential for targeting PGM1 in CRC therapies.


2012 ◽  
Vol 59 (3) ◽  
pp. 218 ◽  
Author(s):  
Kwan Ho Lee ◽  
Hyung Ook Kim ◽  
Chang Hak Yoo ◽  
Byung Ho Son ◽  
Yong Lai Park ◽  
...  

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Mingyu Zhang ◽  
Huijie Jiang ◽  
Rongjun Zhang ◽  
Hailong Xu ◽  
Hao Jiang ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ziyao Li ◽  
Shaofei Li ◽  
Hangbo Tao ◽  
Yixiang Zhan ◽  
Kemin Ni ◽  
...  

Abstract Background There have been controversial voices on if hepatitis B virus infection decreases the risk of colorectal liver metastases or not. This study aims to the find the association between HBV infection and postoperative survival of colorectal cancer and the risk of liver metastases in colorectal cancer patients. Methods Patients who underwent curative surgical resection for colorectal cancer between January 2011 and December 2012 were included. Patients were grouped according to anti-HBc. Differences in overall survival, time to progress, and hepatic metastasis-free survival between groups and significant predictors were analyzed. Results Three hundred twenty-seven colorectal cancer patients were comprised of 202 anti-HBc negative cases and 125 anti-HBc positive cases, and anti-HBc positive cases were further divided into high-titer anti-HBc group (39) and low-titer anti-HBc group (86). The high-titer anti-HBc group had significantly worse overall survival (5-Yr, 65.45% vs. 80.06%; P < .001), time to progress (5-Yr, 44.26% vs. 84.73%; P < .001), and hepatic metastasis-free survival (5-Yr, 82.44% vs. 94.58%; P = .029) than the low-titer group. Multivariate model showed anti-HBc ≥ 8.8 S/CO was correlated with poor overall survival (HR, 3.510; 95% CI, 1.718–7.17; P < .001), time to progress (HR, 5.747; 95% CI, 2.789–11.842; P < .001), and hepatic metastasis-free survival (HR, 3.754; 95% CI, 1.054–13.369; P = .041) in the anti-HBc positive cases. Conclusions Higher titer anti-HBc predicts a potential higher risk of liver metastases and a worse survival in anti-HBc positive colorectal cancer patients.


2020 ◽  
Author(s):  
Junwei Tang ◽  
Yifei Feng ◽  
Yuanjian Huang ◽  
Ziwei Xu ◽  
Dongsheng Zhang ◽  
...  

Abstract Background Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “skip” lymph vascular invasion on hepatic metastasis, who presenting poor prognosis. We aiming to investigate the potential mechanism for the “skip” lymph vascular invasion on hepatic metastasis in colorectal cancer. Methods The microarray was applied for screening the transcription landscape of circRNA in lymph node negative CRC patients with synchronous liver metastasis (LNLM1) or without liver metastasis (LNLM0). The gain- and loss-of-function experiments was conducted in CRC cell lines and animal models. The RNA pull-down, RNA immunoprecipitation n was further employed in exploring the detailed mechanism of circRNA and associated target genes. Results We identified the aberrant increased circRNA circ_0124554 (also entitled as circ-LNLM) in tumor tissues of LNLM1 patients comparing with either the tumor tissues of LNLM0 or adjacent tissues of LNLM1. Circ-LNLM1 expression was highly corrected with liver metastasis and vascular invasion. Ectopic expression of cytoplasmic located circ-LNLM could promote invasion of CRC cells and induced the liver metastasis in animal models through the direct binding with AKT. The phosphorylation of AKT (T308/S473) was activated due to the blocked ubiquitination site of Lys in 0-52aa peptide of circ-LNLM. Endogenous plasma expression of circ-LNLM induced poor prognosis of LNLM1 and could distinguish LNLM1 patients from LNLM0. Conclusions The circ-LNLM blocked the ubiquitination of AKT could promote the early metastasis especially for the lymph node-negative colorectal cancer patients with synchronous liver metastasis. The circ-LNLM might be prognosis and diagnosis biomarker for LNLM1 patients.


10.19082/7364 ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 7364-7369
Author(s):  
Manar Mutlag Alharthi ◽  
Anwar Saeed Alzahrani ◽  
Shaikhah A-Jumaiah ◽  
Mohammed Saad Alqahtani

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15545-e15545
Author(s):  
Honghua Peng ◽  
Tianhao Mu ◽  
Yaping Sheng ◽  
Yingmei Li ◽  
Peiguo Cao

e15545 Background: Hepatic metastasis is the most common site of distant spread from colorectal cancer. About 15-25% patients with colorectal cancer harbors hepatic metastasis. The molecular mechanism and predicting biomarkers in colorectal cancer are still not fully understood. Methods: 57 Chinese colorectal cancer patients were enrolled in a cohort study. Samples of primary tumor were collected in these patients and underwent whole exome sequencing. Mutation profiles of primary tumors between the patients with metastasis and those without metastasis were analyzed and compared. Results: In the cohort, 54.4% (31/57) patients presented hepatic metastasis at the time of diagnosis, while 45.6% (26/57) did not. The patients were divided into 2 groups—with hepatic metastasis and without hepatic metastasis. The mutation landscape of primary tumor indicated that the Top 3 most frequently mutated genes of both groups were the same and presented mutated TP53, APC, and KRAS. 2. Interestingly, compared with the patients without hepatic metastasis, the patients with hepatic metastasis presented a higher frequency of mutated TCF7L2 (35.5% vs 3.85%) and TRIM77 (16.1% vs 0%). Moreover, in the patients with hepatic metastasis, the patients with TRIM77 mutation in primary tumor showed a worse overall survival (p < 0.0001). Conclusions: TCF7L2 and TRIM77 may be identified as potential candidate predicting biomarkers for hepatic metastasis in colorectal patients. In addition, mutated TRIM 77 predicted a poor overall survival in hepatic metastasis from colorectal cancer.


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