scholarly journals Identifying metastasis-initiating miRNA-target regulations of colorectal cancer from expressional changes in primary tumors

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jongmin Lee ◽  
Hye Kyung Hong ◽  
Sheng-Bin Peng ◽  
Tae Won Kim ◽  
Woo Yong Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Mirna Target ◽  
Target Genes ◽  
Expression Profiles ◽  
Statistical Significance ◽  
Primary Tumors ◽  
Significant Difference

Abstract Colorectal cancer (CRC) is prevalent with high mortality, with liver metastasis contributing as a major factor that worsens the survival of patients. The roles of miRNAs in CRC have been elucidated, subsequent to recent studies that suggest the involvement of miRNAs in cancer biology. In this study, we compare the miRNA and gene expression profiles of primary tumors between two groups of patients (with and without liver metastasis) to identify the metastasis-initiating microRNA-target gene regulations. Analysis from 33 patients with metastasis and 14 patients without metastasis revealed that 17 miRNAs and their 198 predicted target genes are differentially expressed, where the target genes showed association with cancer progression and metastasis with statistical significance. In order to evaluate the clinical implications of the findings, we classified CRC patients of independent data into two groups based on the identified miRNA-target regulations, where one group was closer to primary tumors with metastasis than the other group. The comparison of survival showed statistically significant difference, thereby implying the roles of the identified miRNA-target regulations in cancer progression and metastasis. The identification of metastasis-initiating miRNA-target regulations in this study will lead to better understanding of the roles of miRNAs in CRC progression.

Overexpression of GLUT1 in Colorectal Cancer is Independently Associated with Poor Prognosis

2011 ◽  
Vol 26 (3) ◽  
pp. 166-172 ◽  
Author(s):  
Yang-Mei Shen ◽  
Gunnar Arbman ◽  
Birgit Olsson ◽  
Xiao-Feng Sun
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Poor Prognosis ◽  
Glucose Transporter ◽  
Normal Mucosa ◽  
Stage I ◽  
Primary Tumors ◽  
Glucose Transporter 1 ◽  
Significant Difference ◽  
Glut1 Expression

Background To investigate the expression of glucose transporter 1 (GLUT1) in colorectal cancer (CRC) and its relationship to clinicopathological variables. Methods The expression of GLUT1 in 163 primary tumors together with the corresponding normal mucosa, and 36 liver metastases was examined using real-time PCR. Results The mean value of GLUT1 was higher in primary tumors (50.390 ± 68.648) than in the corresponding normal mucosa (20.437 ± 28.703, p<0.0001), while there was no significant difference in GLUT1 expression between CRC and liver metastasis (50.390 ± 68.648 vs 52.277 ± 52.482, p=0.190). In CRCs, GLUT1 expression was higher in poorly differentiated than in well and moderately differentiated tumors (p=0.022), and higher in stage III + IV than in stage I + II tumors (p=0.035). The patients with high-expressed GLUT1 had a worse prognosis than those with low-expressed GLUT1 independently of gender, age, tumor site, stage and differentiation (p=0.026, RR 2.737, 95% CI 1.126–6.651) in stage I-III CRCs. In liver metastasis, GLUT1 expression was higher in larger tumors than in smaller ones (p=0.025). Conclusions Overexpression of GLUT1 in stage I-III CRCs was independently associated with poor prognosis.

scholarly journals The Dual Role of MicroRNAs in Colorectal Cancer Progression

2018 ◽  
Vol 19 (9) ◽  
pp. 2791 ◽  
Author(s):  
Lei Ding ◽  
Zhenwei Lan ◽  
Xianhui Xiong ◽  
Hongshun Ao ◽  
Yingting Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Profiles ◽  
Dual Role ◽  
Aberrant Expression ◽  
Cellular Environment ◽  
Incidence And Mortality ◽  
Context Specific

Colorectal cancer (CRC) is responsible for one of the major cancer incidence and mortality worldwide. It is well known that MicroRNAs (miRNAs) play vital roles in maintaining the cell development and other physiological processes, as well as, the aberrant expression of numerous miRNAs involved in CRC progression. MiRNAs are a class of small, endogenous, non-coding, single-stranded RNAs that bind to the 3’-untranslated region (3′-UTR) complementary sequences of their target mRNA, resulting in mRNA degradation or inhibition of its translation as a post-transcriptional regulators. Moreover, miRNAs also can target the long non-coding RNA (lncRNA) to regulate the expression of its target genes involved in proliferation and metastasis of CRC. The functions of these dysregulated miRNAs appear to be context specific, with evidence of having a dual role in both oncogenes and tumor suppression depending on the cellular environment in which they are expressed. Therefore, the unique expression profiles of miRNAs relate to the diagnosis, prognosis, and therapeutic outcome in CRC. In this review, we focused on several oncogenic and tumor-suppressive miRNAs specific to CRC, and assess their functions to uncover the molecular mechanisms of tumor initiation and progression in CRC. These data promised that miRNAs can be used as early detection biomarkers and potential therapeutic target in CRC patients.

scholarly journals Keap1 deletion accelerates mutant K-ras/p53-driven cholangiocarcinoma

2020 ◽  
Vol 318 (3) ◽  
pp. G419-G427 ◽  
Author(s):  
Tatsuhide Nabeshima ◽  
Shin Hamada ◽  
Keiko Taguchi ◽  
Yu Tanaka ◽  
Ryotaro Matsumoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Progression ◽  
Stress Responses ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Related Factor ◽  
Loss Of Function ◽  
P53 Expression ◽  
Nrf2 Activation

The activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) pathway contributes to cancer progression in addition to oxidative stress responses. Loss-of-function Keap1 mutations were reported to activate Nrf2, leading to cancer progression. We examined the effects of Keap1 deletion in a cholangiocarcinoma mouse model using a mutant K-ras/ p53 mouse. Introduction of the Keap1 deletion into liver-specific mutant K-ras/ p53 expression resulted in the formation of invasive cholangiocarcinoma. Comprehensive analyses of the gene expression profiles identified broad upregulation of Nrf2-target genes such as Nqo1 and Gstm1 in the Keap1-deleted mutant K-ras/ p53 expressing livers, accompanied by upregulation of cholangiocyte-related genes. Among these genes, the transcriptional factor Sox9 was highly expressed in the dysplastic bile duct. The Keap-Nrf2-Sox9 axis might serve as a novel therapeutic target for cholangiocarcinoma. NEW & NOTEWORTHY The Keap1-Nrf2 system has a wide variety of effects in addition to the oxidative stress response in cancer cells. Addition of the liver-specific Keap1 deletion to mice harboring mutant K-ras and p53 accelerated cholangiocarcinoma formation, together with the hallmarks of Nrf2 activation. This process involved the expansion of Sox9-positive cells, indicating increased differentiation toward the cholangiocyte phenotype.

scholarly journals The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases

2018 ◽  
Vol 19 (12) ◽  
pp. 3711 ◽  
Author(s):  
Ovidiu Balacescu ◽  
Daniel Sur ◽  
Calin Cainap ◽  
Simona Visan ◽  
Daniel Cruceriu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Cancer Progression ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Cancer Management ◽  
Incidence And Mortality ◽  
The Impact

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality rate. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial–mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.

Carcinoembryonic antigen and matrix metalloproteinase 2 serum and peritoneal washes concentration in staging and prognosis in colorectal cancer patients

2018 ◽  
Vol 90 (5) ◽  
pp. 36-43
Author(s):  
Tomasz Guzel ◽  
Dagmara Mirowska-Guzel ◽  
Gustaw Lech ◽  
Marek Wroński ◽  
Marzena Iwanowska ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Matrix Metalloproteinase ◽  
Tumor Staging ◽  
Statistical Significance ◽  
Matrix Metalloproteinase 2 ◽  
Curative Surgery ◽  
P Concentration ◽  
Preoperative Serum ◽  
Significant Difference

Abstract Purpose: The aim of the study was to determine of carcinoembryonal antigen and matrix metalloproteinase 2 peritoneal washes and serum concentration in patients suffering from colorectal cancer concerning tumor staging and 5-year survival rate in these patients. Methods: 80 patients who underwent curative surgery for colorectal cancer were included into the study. Preoperative serum and intraoperative peritoneal washes CEA and MMP-2 concentrations were measured. Results: Concerning tumor penetration CEA-s and CEA-p concentration was higher in subsequent stages from T2 to T4. Both CEA-s and CEA-p concentration was lower in T2 comparing to T3 and T4. Significant difference of CEA-s and CEA-p was noted between T2 and T4 stages. MMP2-s concentration was higher in T3 comparing to T2, the highest MMP2-p concentration was in T4, with no statistical significance. Concerning nodular status significant difference of CEA-s was noted between N0 and N1. For CEA-p significance was found between N0 and N2 as between N1 and N2. MMP2-s concentration was the highest in N1, MMP2-p concentration was the highest in T4, with no statistical significance. 5-year survival rate for all patients was 63,53%. There were significant differences in CEA-s and CEA-p concentration between patients with negative and positive 5-year survival. Conclusion: Intraoperative peritoneal washes concentration of CEA may potentially serve as an important factor for more precise colorectal cancer staging. CEA-p and CEA-s concentration correlates with survival rate in patients suffering from colorectal cancer and can be useful as an additional prognostic factor. Usefulness of MMP2 measurement still requires further studies.

Personalized therapy for metastatic colorectal cancer: A closer possibility?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4131-4131
Author(s):  
M. Pierobon ◽  
V. Calvert ◽  
M. Lipsky ◽  
K. Sheehan ◽  
R. Speer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Liver Metastasis ◽  
Signaling Pathways ◽  
Hepatic Metastases ◽  
Protein Microarrays ◽  
Western World ◽  
Specific Cell ◽  
Molecular Fingerprint ◽  
Primary Tumors

4131 Background: Colorectal cancer (CRC) is the second leading cause of cancer related death in the Western world, and survival rate is closely associated with the development of metastases. Personalized targeted therapies promise to have a dramatic impact on the treatment of cancer over the next decade. The molecular fingerprint of a patient’s tumor is the basis for specific targeted therapy. Most often, we are not measuring what we are treating. If we choose therapy based on the primary tumor, but we are treating the metastasis, we are likely giving the wrong therapy if the two microenvironments are not equivalent. In this study we employed reverse phase protein microarrays (RPPA) to compare the protein kinases signal pathway derangements in the primary CRC and in its synchronous liver metastasis. Methods: Pure cell populations of 34 cases of patient-matched CRC and hepatic metastases (collected at the same surgical time) were isolated through laser capture microdissection and then lysed. The lysed cells were evaluated using RPPA technology that allowed us to analyze the activation status of 80 different kinases. Data analysis was performed using commercially available software. Results: Of the 80 kinases only 20 endpoints were significantly (p< 0.05) altered between the two populations. These endpoints were contained within just a few signaling pathways, including the PI3K-AKT prosurvival pathway and the c-kit/PDGFr/c-abl growth factor pathway. We noted a significant increase in phosphorylation of AKT along with a decrease in phosphorylation of PTEN in the liver metastasis compared to the matched primary tumors. This is in keeping with what is known about AKT since phosphorylation of PTEN serves to destabilize the protein, which serves as a natural upstream suppressor of AKT kinase. Conclusions: Specific cell signaling pathways, such as the PI3K-AKT and the c-kit/PDGFr/c-abl growth factor signaling pathway, are significantly altered and activated in hepatic metastasis compared to the primary colorectal site. Since the data reveals elevation in kinase activity increases on a pathway-wide level, a rational hypothesis can be developed whereby combinations of drugs such as an AKT- mTOR inhibitor and/or Gleevec may be an effective and novel therapeutic strategy for the treatment of metastatic CRC. No significant financial relationships to disclose.

scholarly journals Identification of Hub Genes Related to Liver Metastasis of Colorectal Cancer by Integrative Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Sicheng Liu ◽  
Yaguang Zhang ◽  
Su Zhang ◽  
Lei Qiu ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Expression Profiles ◽  
Interaction Network ◽  
Rank Aggregation ◽  
Marker Genes ◽  
Peroxisome Proliferator ◽  
Hub Genes ◽  
Peroxisome Proliferator Activated Receptor ◽  
New Biomarkers

Liver metastasis of colorectal cancer (LMCRC) severely damages patient health, causing poor prognosis and tumor relapse. Marker genes associated with LMCRC identified by previous study did not meet therapeutic demand. Therefore, it is necessary to identify new biomarkers regulating the metastasis network and screen potential drugs for future treatment. Here, we identified that cell adhesion molecules and peroxisome proliferator-activated receptor (PPAR) signaling pathway were significantly enriched by analyzing the integrated-multiple expression profiles. Moreover, analysis with robust rank aggregation approach revealed a total of 138 differentially expressed genes (DEGs), including 108 upexpressed and 30 downexpressed genes. With establishing protein–protein interaction network, we also identified the subnetwork significantly enriching the metastasis-associated hub genes including ALB, APOE, CDH2, and ORM1. ESR2, FOXO3, and SRY were determined as key transcription factors regulating hub genes. In addition, ADH-1, epigallocatechin, CHEMBL1945287, and cochinchinenin C were predicted as potential therapeutic drugs. Moreover, the antimigration capacity of ADH-1 and epigallocatechin were confirmed in CRC cell lines. In conclusion, our findings not only offer opportunities to understand metastasis mechanism but also identify potential therapeutic targets for CRC.

scholarly journals The olfactory receptor gene OR56A4 is differentially expressed based on disease stage in breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Olfactory Receptor ◽  
Expression Profiles ◽  
Receptor Gene ◽  
Gene Expression Profiles ◽  
Stage I ◽  
Stage Iii ◽  
Disease Stage ◽  
Primary Tumors

To understand the transcriptional behavior that accompanies breast cancer progression, we compared the global gene expression profiles of 100 tumors at stages I, II and III using two independent published microarray datasets (1, 2). We found that the olfactory receptor, family 56, subfamily A, member 4 OR56A4 was among the genes whose expression was most different when comparing stage I, stage II, and stage III primary tumors from patients with breast cancer. OR56A4 expression was lower in stage III tumors as opposed to stage I tumors.

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