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Peroxireduxin-4 is over-expressed in colon cancer and its down-regulation leads to apoptosis

ABSTRACT: The objective of this study was to gain insights into the biological basis of colon cancer progression by characterizing gene expression differences between normal colon epithelium, corresponding colorectal primary tumors and metastases. We found a close similarity in gene expression patterns between primary tumors and metastases, indicating a correlation between gene expression and morphological characteristics. PRDX4 was identified as highly expressed both in primary colon tumors and metastases, and selected for further characterization. Our study revealed that Prdx4 (PrxIV, AOE372) shows functional similarities to other Prx family members by negatively effecting apoptosis induction in tumor cells. In addition, our studies link Prdx4 with Hif-1M-NM-1, a key regulatory factor of angiogenesis. Targeting Prdx4 may be an attractive approach in cancer therapy, as its inhibition is expected to lead to induction of apoptosis and blockade of Hif-1M-NM-1-mediated tumor angiogenesis. mRNA expression profiling of normal colon epithelium (5), primary colon tumors (12 with 1 replicate) and either lymph node metastases (9 with 2 replicates) or liver metastases (2) and cell lines (4) from twelve colon cancer patients.

ORGANISM(S): Homo sapiens

SUBMITTER: Norbert Schweifer

PROVIDER: E-GEOD-26571 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Peroxireduxin-4 is over-expressed in colon cancer and its down-regulation leads to apoptosis

Project description:The objective of this study was to gain insights into the biological basis of colon cancer progression by characterizing gene expression differences between normal colon epithelium, corresponding colorectal primary tumors and metastases. We found a close similarity in gene expression patterns between primary tumors and metastases, indicating a correlation between gene expression and morphological characteristics. PRDX4 was identified as highly expressed both in primary colon tumors and metastases, and selected for further characterization. Our study revealed that Prdx4 (PrxIV, AOE372) shows functional similarities to other Prx family members by negatively effecting apoptosis induction in tumor cells. In addition, our studies link Prdx4 with Hif-1α, a key regulatory factor of angiogenesis. Targeting Prdx4 may be an attractive approach in cancer therapy, as its inhibition is expected to lead to induction of apoptosis and blockade of Hif-1α-mediated tumor angiogenesis.

2011-06-01 | GSE26571 | GEO

Gene expression profiling of primary tumors, lymph node and liver metastases in midgut carcinoid tumors.

Project description:In order to clarify the gene expression and identify genes involved in tumor progression, gene expression profiling was performed on tumor specimens. Samples comprised 18 primary tumors, 17 lymph node (LN) metastases and 7 liver metastases. Patients were grouped according to clinical data and histopathology into indolent or progressive course. RNA was subjected to a spotted oligo microarray and B-statistics were performed. Differentially expressed genes were verified using quantitative RT-PCR. Self-organising maps demonstrated three clusters. Eleven primary tumors separated in one cluster, 5 LN metastases in another whereas all liver metastases, 7 primary and 12 LN metastases, formed a third cluster. There was no correlation between indolent and progressive behaviour. The primary tumors with Ki67 > 5%, with low frequency of the carcinoid syndrome and a tendency towards shorter survival grouped together. Primary tumors differed in expression profile from their associated LN metastases. ACTG2, GREM2, REG3A, TUSC2, RUNX1, TPH1, TGFBR2 and CDH6 were differentially expressed between clusters and subgroups of tumors. The expression profile that assembles tumors as being genetically similar on the RNA expression level may not be concordant with the clinical disease course. This study reveals different gene expression profiles and novel genes not previously known to be involved in neuroendocrine tumorigenesis, and which may be of importance for tumor progression. Gene expression comparisons between 18 primary tumors, 17 lymph node metastases and 7 liver metastases.

2011-02-10 | E-GEOD-27162 | biostudies-arrayexpress

Association of microRNAs with colon tumor metastases

2014-08-01 | GSE44121 | GEO

Identification of brain metastasis vulnerabilities using METPlatform

Project description:Exclusion of cancer patients with brain metastases from clinical trials is a major cause of the limited therapeutic options available for secondary brain tumors. Here, we report a novel drug-screening platform (METPlatform) based on organotypic cultures that allows identifying anti-metastatic compounds in a preparation that includes the tumor microenvironment. By applying this approach to brain metastasis, we identified HSP90 as a promising therapeutic target. A blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases from melanoma, lung and breast adenocarcinoma with distinct oncogenomic profiles at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis of brain metastases treated with the chaperone inhibitor revealed non-canonical clients of HSP90 as potential novel mediators of brain metastasis and actionable mechanisms of resistance driven by autophagy. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is fully compatible with human samples. We envision that METPlatform could be established as a clinically relevant strategy to personalize the management of metastatic disease in the brain and elsewhere.

2022-03-17 | PXD020092 | Pride

Association of microRNAs with colon tumor metastases

Project description:We compared the expression of microRNAs in primary colon tumors with their paired liver metastases using the Nanostring human microRNA assays version 1 23 microRNAs were found to be differentially expressed between colon primary tumors and their paired metastases Total mRNA was extracted from flash frozen primary colon tumors and paired metastases. 18 tissues from 9 donors were used for this study. 100 ng of RNA was hybridized to Nanostring Human 0microRNA assays version 1.0. Data was normalized according to manufacterer's recommendation. This included background substraction and normalizing to the geometric mean of the highest 75 microRNAs.

2014-08-01 | E-GEOD-44121 | biostudies-arrayexpress

ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone

Project description:Bone is the primary site of breast cancer metastasis and complications associated with bone metastases can lead to a significantly decreased quality of life in these patients. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. Methods: To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene expression profiles from laser capture micro-dissected trephine biopsies of both breast cancer bone metastases and primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared to primary mammary tumors. Results: ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary mammary tumors. In addition, ABCC5 was significantly up-regulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 significant reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers. Conclusions: Our data, for the first time, suggests that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for the efficient bone resorption mediated by osteoclasts. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis. primary breast tumors vs. bone trephine biopsies

2012-11-09 | E-GEOD-39494 | biostudies-arrayexpress

Specific extracellular matrix remodeling signature of colon hepatic metastases

Project description:To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment. 57 samples of patients with stage IV colorectal cancer. We compared using Affymetrix chips gene expression profiles between primary tumors and hepatic metastases

2013-09-01 | E-GEOD-49355 | biostudies-arrayexpress

Specific extracellular matrix remodeling signature of colon hepatic metastases [HG-U133B]

2014-10-15 | E-GEOD-62321 | biostudies-arrayexpress

Expression data from xenograft tumors derived from LoVo colon cancer lines +/- constitutive LIN28B expression

Project description:We sought to elucidate functions of LIN28B and potential mechanisms whereby it may promote metastasis by comparing the gene expression profile of LIN28B metastases to primary tumors. Accordingly, we performed microarray analysis on total RNA isolated from empty vector tumors, LIN28B-LoVo tumors, and LIN28B-LoVo metastases Constitutive LIN28B expression was achieved in the LoVo (ATCC #CCL-229) colon cancer cell line via retroviral transduction of MSCV-PIG-LIN28B. xenografts were produced via injection of 1x106 cells subcutaneously into the rear flanks of nude mice. Microarrays were conducted on primary tumors from empty vector and LIN28B-expressing cells, as well as metastases derived from primary tumors constitutively expressing LIN28B. (Note: metastases did not occur with empty vector tumors)

2010-12-29 | E-GEOD-26335 | biostudies-arrayexpress

Molecular Profiling of Metastatic Prostate Carcinoma Reveals Substantial Inter-individual and Limited Intra-individual Diversity: Implications for Precision Oncology

Project description:Prostate cancers exhibit a spectrum of molecular aberrations of which a substantial subset are amenable to targeted therapeutics. To determine the diversity of somatic alterations present in metastasis within and between individuals we characterized the genomic landscapes of 176 tumors acquired from 63 men. In contrast to the considerable variation across individuals, the molecular diversity of tumors within an individual was substantially less: alterations in putative drivers of cancer growth and cell cycle progression status were highly concordant. While androgen receptor activity was inversely related to proliferation, the expression of Fanconi Anemia complex genes was strongly associated with increased cell cycle progression. Inhibition of FANCA, FANCC, FANCD2 and BRCA2 expression reduced prostate cancer growth. The limited molecular diversity across metastases may result from bottlenecks imposed by the dissemination process, limited evolutionary time between metastatic seeding and tumor sampling, intermixing of tumor clones, and selection resulting from treatment pressures. Though exceptions exist, evaluating a single metastasis provides a reasonable assessment of the key molecular processes that occur throughout the spectrum of disseminated tumors within an individual, and may be used for selecting treatments based on predicted molecular vulnerabilities. Custom Agilent 44K whole human genome expression oligonucleotide microarrays were used to profile 171 CRPC tumors from 63 patients. RNA was amplified prior to hybridization against a common reference pool of prostate tumor cell lines.

2015-12-18 | E-GEOD-74685 | biostudies-arrayexpress

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