scholarly journals Differential microRNA expression profiling in primary tumors and matched liver metastasis of patients with colorectal cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (22) ◽  
pp. 35783-35791 ◽  
Author(s):  
Wenhua Li ◽  
Jinjia Chang ◽  
Duo Tong ◽  
Junjie Peng ◽  
Dan Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Expression Profiling ◽  
Microrna Expression ◽  
Primary Tumors

scholarly journals De novo transcriptomic subtyping of colorectal cancer liver metastases in the context of tumor heterogeneity

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Seyed H. Moosavi ◽  
Peter W. Eide ◽  
Ina A. Eilertsen ◽  
Tuva H. Brunsell ◽  
Kaja C. G. Berg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Expression Profiling ◽  
Tumor Heterogeneity ◽  
Progenitor Cell ◽  
De Novo ◽  
Primary Tumors ◽  
Malignant Liver

Abstract Background Gene expression-based subtyping has the potential to form a new paradigm for stratified treatment of colorectal cancer. However, current frameworks are based on the transcriptomic profiles of primary tumors, and metastatic heterogeneity is a challenge. Here we aimed to develop a de novo metastasis-oriented framework. Methods In total, 829 transcriptomic profiles from patients with colorectal cancer were analyzed, including primary tumors, liver metastases, and non-malignant liver samples. High-resolution microarray gene expression profiling was performed of 283 liver metastases from 171 patients treated by hepatic resection, including multiregional and/or multi-metastatic samples from each of 47 patients. A single randomly selected liver metastasis sample from each patient was used for unsupervised subtype discovery by nonnegative matrix factorization, and a random forest prediction model was trained to classify multi-metastatic samples, as well as liver metastases from two independent series of 308 additional patients. Results Initial comparisons with non-malignant liver samples and primary colorectal tumors showed a highly variable degree of influence from the liver microenvironment in metastases, which contributed to inter-metastatic transcriptomic heterogeneity, but did not define subtype distinctions. The de novo liver metastasis subtype (LMS) framework recapitulated the main distinction between epithelial-like and mesenchymal-like tumors, with a strong immune and stromal component only in the latter. We also identified biologically distinct epithelial-like subtypes originating from different progenitor cell types. LMS1 metastases had several transcriptomic features of cancer aggressiveness, including secretory progenitor cell origin, oncogenic addictions, and microsatellite instability in a microsatellite stable background, as well as frequent RAS/TP53 co-mutations. The poor-prognostic association of LMS1 metastases was independent of mutation status, clinicopathological variables, and current subtyping frameworks (consensus molecular subtypes and colorectal cancer intrinsic subtypes). LMS1 was also the least heterogeneous subtype in comparisons of multiple metastases per patient, and tumor heterogeneity did not confound the prognostic value of LMS1. Conclusions We report the first large study of multi-metastatic gene expression profiling of colorectal cancer. The new metastasis-oriented subtyping framework showed potential for clinically relevant transcriptomic classification in the context of metastatic heterogeneity, and an LMS1 mini-classifier was constructed to facilitate prognostic stratification and further clinical testing.

Identification of high-risk Dukes B colorectal cancer by microRNA expression profiling: a preliminary study

2015 ◽  
Vol 17 (7) ◽  
pp. 578-588 ◽  
Author(s):  
M. I. Aslam ◽  
J. Venkatesh ◽  
J. S. Jameson ◽  
K. West ◽  
J. H. Pringle ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Expression Profiling ◽  
Microrna Expression ◽  
Preliminary Study

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.

scholarly journals MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer

2012 ◽  
Vol 106 (7) ◽  
pp. 1320-1330 ◽  
Author(s):  
X T Xu ◽  
Q Xu ◽  
J L Tong ◽  
M M Zhu ◽  
F Nie ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Expression Profiling ◽  
Microrna Expression

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 PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiao-Li Wei ◽  
Xuan Luo ◽  
Hui Sheng ◽  
Yun Wang ◽  
Dong-Liang Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Checkpoint Inhibitors ◽  
Tissue Microarrays ◽  
Tumor Differentiation ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Expression Cluster

Abstract Background The outcomes of immune checkpoint inhibitors in cancer patients with liver metastases are poor, which may be related to a different tumor microenvironment in liver metastases from primary tumors. This study was aimed to analyze PD-L1 expression and the immune microenvironment status in liver metastases and compare the differences of PD-L1 expression between primary tumors and liver metastases of colorectal cancer. Methods 74 cases of pathologically confirmed colorectal cancer with liver metastasis underwent resection from our hospital were included. Tissue microarrays were used for the interpretation of PD-L1 expression, cluster of differentiation 4 (CD4) and CD8 density by immunohistochemistry. We evaluated the disparity between primary tumor and liver metastasis in PD-L1 expression, CD4 and CD8 density and analyzed the factors associated with obvious PD-L1 disparity. Results The expression of PD-L1 was positively related to the density of CD4 and CD8 in liver metastases. The expression of PD-L1 in liver metastases was higher than in primary tumors in certain subgroups, including patients with concurrent liver metastases (n = 63, p = 0.05), patients receiving concurrent resection of primary and metastatic tumors (n = 56, p = 0.04). The two subgroups generally reflected those without inconsistent external influences, such as treatment and temporal factors, between primary tumors and liver metastases. In these subgroups, the intrinsic differences of microenvironment between primary tumors and liver metastases could be identified. Furthermore, tumor differentiation [moderate vs. poor: OR = 0.23, 95% CI: 0.03–0.99, p = 0.05)] were demonstrated to be associated with obvious discordance of PD-L1 expression between primary tumors and liver metastases. Conclusions The expression of PD-L1 in liver metastases was higher than in primary tumors in subgroups, reflecting intrinsic microenvironment differences between primary and metastatic tumors. Obvious discordance of PD-L1 expression between primary tumor and liver metastasis was significantly related to the tumor differentiation.

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