scholarly journals Consensus molecular subtypes of primary colon tumors and their hepatic metastases

2021 ◽  
pp. FSO722
Author(s):  
Yee Chen Lau ◽  
Sebastian Schmeier ◽  
Frank Frizelle ◽  
Rachel Purcell
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Molecular Subtypes ◽  
Expression Profiles ◽  
Hepatic Metastases ◽  
Gene Expression Profiles ◽  
Colorectal Tumors ◽  
Primary Colorectal Cancer ◽  
Primary Tumors ◽  
Primary Colon

Aim: This pilot study aimed to evaluate the congruency in consensus molecular subtypes (CMS) of primary colorectal cancer and corresponding hepatic metastasis (HM). Materials & methods: RNA was extracted from both primary colorectal cancer and HM from ten patients, sequenced to establish gene-expression profiles and classified into CMS. Clinical data were collected retrospectively. Results: Of the ten patients recruited, nine had primary tumors that were classifiable: seven were CMS2, one was CMS3 and one was CMS4. Five had incongruent classification in the corresponding HM. Three out of the five patients with incongruent classification had received adjuvant chemotherapy prior to hepatic resection. Conclusion: A change in CMS type between matched primary and metastatic colorectal tumors is common and may be attributable to chemotherapy.

Epigenetically regulated gene expression profiles reveal four molecular subtypes with prognostic and therapeutic implications in colorectal cancer

2020 ◽  
Author(s):  
Xiaokang Wang ◽  
Jinfeng Liu ◽  
Danwen Wang ◽  
Maohui Feng ◽  
Xiongzhi Wu
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Metabolic Activity ◽  
Poor Prognosis ◽  
Molecular Subtypes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Epigenetic Mechanisms ◽  
Regulated Gene Expression ◽  
Marked Proliferation

Abstract Transcriptomic deregulation by epigenetic mechanisms plays a crucial role in the heterogeneous progression of colorectal cancer (CRC). Herein, we first demonstrated that the frequencies of the aberrancies of DNA methylation-correlated (METcor) and microRNA (miRNA)-correlated (MIRcor) genes were significantly co-regulated. Next, through integrative clustering of the expression profiles of METcor and MIRcor genes, four molecular subtypes were identified in CRC patients from The Cancer Genome Atlas and then validated in four independent datasets. More importantly, the four subtypes were well characterized and showed distinct clinical and molecular features: (i) S-I: high metabolic activity, sensitive to 5-fluorouracil-based chemotherapy and good prognosis; (ii) S-II: moderate metabolic activity, marked proliferation, frequent KRAS mutation and intermediate prognosis; (iii) S-III: moderate metabolic activity, marked proliferation, promoter DNA hypermethylation, high mutation burden, frequent BRAF and EGFR mutations, moderate levels of epithelial-mesenchymal transition (EMT) and transforming growth factor β (TGFβ) signals, immune-inflamed phenotype, sensitive to cetuximab and death protein-1 inhibitor treatment and relatively poor prognosis and (iv) S-IV: miRNA overexpression, stem/serrated/mesenchymal-like properties, hypoxia, high levels of EMT and TGFβ signals, immune-excluded phenotype and poor prognosis. Overall, this study established a molecular classification based on epigenetically regulated gene expression profiles, thereby providing a better understanding of the epigenetic mechanisms underlying CRC heterogeneity.

scholarly journals Tribbles Gene Expression Profiles in Colorectal Cancer

2021 ◽  
Vol 3 (4) ◽  
pp. 218-236
Author(s):  
Mónica T. Fernandes ◽  
Victor Yassuda ◽  
José Bragança ◽  
Wolfgang Link ◽  
Bibiana I. Ferreira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Early Stage ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Bioinformatic Analysis ◽  
Future Research ◽  
Data Sets ◽  
Experimental Conditions ◽  
Primary Tumors

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death due to cancer in the world. Therefore, the identification of novel druggable targets is urgently needed. Tribbles proteins belong to a pseudokinase family, previously recognized in CRC as oncogenes and potential therapeutic targets. Here, we analyzed the expression of TRIB1, TRIB2, and TRIB3 simultaneously in 33 data sets from CRC based on available GEO profiles. We show that all three Tribbles genes are overrepresented in CRC cell lines and primary tumors, though depending on specific features of the CRC samples. Higher expression of TRIB2 in the tumor microenvironment and TRIB3 overexpression in an early stage of CRC development, unveil a potential and unexplored role for these proteins in the context of CRC. Differential Tribbles expression was also explored in diverse cellular experimental conditions where either genetic or pharmacological approaches were used, providing novel hints for future research. This comprehensive bioinformatic analysis provides new insights into Tribbles gene expression and transcript regulation in CRC.

scholarly journals Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Peter W. Eide ◽  
Seyed H. Moosavi ◽  
Ina A. Eilertsen ◽  
Tuva H. Brunsell ◽  
Jonas Langerud ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Principal Components ◽  
Prognostic Value ◽  
Tumor Heterogeneity ◽  
Molecular Subtypes ◽  
R Package ◽  
Data Set ◽  
Primary Tumors ◽  
External Data

AbstractGene expression-based subtypes of colorectal cancer have clinical relevance, but the representativeness of primary tumors and the consensus molecular subtypes (CMS) for metastatic cancers is not well known. We investigated the metastatic heterogeneity of CMS. The best approach to subtype translation was delineated by comparisons of transcriptomic profiles from 317 primary tumors and 295 liver metastases, including multi-metastatic samples from 45 patients and 14 primary-metastasis sets. Associations were validated in an external data set (n = 618). Projection of metastases onto principal components of primary tumors showed that metastases were depleted of CMS1-immune/CMS3-metabolic signals, enriched for CMS4-mesenchymal/stromal signals, and heavily influenced by the microenvironment. The tailored CMS classifier (available in an updated version of the R package CMScaller) therefore implemented an approach to regress out the liver tissue background. The majority of classified metastases were either CMS2 or CMS4. Nonetheless, subtype switching and inter-metastatic CMS heterogeneity were frequent and increased with sampling intensity. Poor-prognostic value of CMS1/3 metastases was consistent in the context of intra-patient tumor heterogeneity.

Gene Expression Profiles as Predictors of Poor Outcomes in Stage II Colorectal Cancer: A Systematic Review and Meta-analysis

2009 ◽  
Vol 8 (4) ◽  
pp. 207-214 ◽  
Author(s):  
An-Ting T. Lu ◽  
Shelley R. Salpeter ◽  
Anthony E. Reeve ◽  
Steven Eschrich ◽  
Patrick G. Johnston ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Systematic Review ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Gene Expression Profiles ◽  
Stage Ii ◽  
Stage Ii Colorectal Cancer ◽  
Poor Outcomes

Analysis of Gene Expression Profiles Reveals Novel Correlations With the Clinical Course of Colorectal Cancer

2007 ◽  
Vol 16 (11) ◽  
pp. 535-548 ◽  
Author(s):  
Duccio Cavalieri ◽  
Piero Dolara ◽  
Enrico Mini ◽  
Cristina Luceri ◽  
Cinzia Castagnini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Clinical Course ◽  
Expression Profiles ◽  
Gene Expression Profiles

Abstract 5711: Gene expression profiles inBRAF V600Emutant colorectal cancer and association withSFRP2methylation status

2017 ◽  
Author(s):  
Kazuya Yasui ◽  
Takeshi Nagasaka ◽  
Toshiaki Toshima ◽  
Takashi Kawai ◽  
Kunitoshi Shigeyasu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Expression Profiles ◽  
Gene Expression Profiles

Different gene expression profiles in metastasizing midgut carcinoid tumors

2011 ◽  
Vol 18 (4) ◽  
pp. 479-489 ◽  
Author(s):  
Katarina Edfeldt ◽  
Peyman Björklund ◽  
Göran Åkerström ◽  
Gunnar Westin ◽  
Per Hellman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Metastases ◽  
Tumor Progression ◽  
Expression Profile ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Carcinoid Tumors ◽  
Disease Course ◽  
Primary Tumors ◽  
Midgut Carcinoid

The genetic events leading the progression of midgut carcinoid tumors are largely unknown. The disease course varies from patient to patient, and there is a lack of reliable prognostic markers. In order to 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 seven liver metastases from a total of 19 patients. 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 real-time PCR. Self-organizing maps demonstrated three clusters: 11 primary tumors separated in one cluster, five LN metastases in another cluster, whereas all seven liver metastases, seven primary, and 12 LN metastases formed a third cluster. There was no correlation between indolent and progressive behavior. The primary tumors with Ki67 >5%, with low frequency of the carcinoid syndrome, and a tendency toward shorter survival grouped together. Primary tumors differed in expression profile from their associated LN metastases; thus, there is evidence for genetic changes from primary tumors to metastases.ACTG2, GREM2, REG3A, TUSC2, RUNX1, TPH1, TGFBR2, andCDH6were 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 differences in gene expression profiles and novel genes that may be of importance in midgut carcinoid tumor progression.

Translation of gene expression profiles into a nine antibody IHC multivariate index assay for colorectal carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21042-21042
Author(s):  
M. T. Schreeder ◽  
R. S. Seitz ◽  
R. Beck ◽  
B. Z. Ring ◽  
D. T. Ross
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Early Stage Disease ◽  
Primary Tumors ◽  
Pathologic Stage ◽  
Predicting Outcome ◽  
Antibody Panel

21042 Introduction: Pathologic stage is the most powerful predictor of outcome in colorectal cancer. However, in early stage disease there continues to be a need for better identification of patients at high risk of disease progression after surgical resection. We have undertaken a large scale effort translating gene expression profiles into immunohistochemical biomarkers that classify carcinoma in novel ways. Herein we report the identification of a colorectal tailored antibody “panel of diversity” that distinguishes tumor heterogeneity and propose a multivariate index assay (MIA) for predicting outcome. Methods: 744 stage I-III consecutive colon cancer patients treated by the CCIH between 1992 and 2000 were identified. Clinical followup through 2005 was obtained from the tumor registry and verified by chart review . Tissue micorarrays (TMA) were constructed from these patients resected primary tumors. Over 700 antibodies targeted by carcinoma gene expression experiments or literature review were first screened on a 30 case TMA. Of these, 34 were selected as showing subjectively high quality stains and the ability to classify patient populations. These antibodies were used to stain the clinical TMA and scored using a semi-quantitative scale. We used a number of approaches including Cox, RPART, and Bayesian to derive candidate MIA's to predict recurrence. Results: 13 antibodies showed a significant or near significant association with either overall recurrence or recurrence at 5 years. We have previously shown these antibodies to have similar prognostic abilities in other solid tumor carcinomas. We propose a model combining nine markers (p53, CCNA2, TFF3, RERG, AKR1C1, TLE3, IRX3, SYP, TTC7) as an MIA for predicting outcome in Stage II patients. The model is independent of pathologic stage. Conclusions: This colon tailored antibody ‘panel of diversity’ is a tool for characterizing the biologic diversity in colon cancer cohorts. The identification of nine prognostic markers that can be effectively combined using an MIA suggests that combination of multiple markers will be useful for developing sensitive and specific prognostic assays. The model proposed herein should be validated using additional cohorts to evaluate its overall clinical utility. No significant financial relationships to disclose.

The relationship between tumor budding, tumor microenvironment, and survival in patients with primary operable colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 581-581
Author(s):  
Hester Catharina Van Wyk ◽  
Antonia K. Roseweir ◽  
Ditte Anderson ◽  
Elizabeth Sutton ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Differential Gene Expression ◽  
Evaluation Method ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Venous Invasion ◽  
Tumour Microenvironment ◽  
Differential Gene ◽  
Tumour Budding

581 Background: Tumour budding is an independent prognostic factor in colorectal cancer and has recently been defined by the International Consensus Conference on Tumour Budding. The aim was to use the ITBCC budding evaluation method to examine relationships between tumour budding, tumour factors, tumour microenvironment, gene expression profiles and survival in patients with primary operable CRC. Methods: Hematoxylin and Eosin (H&E) stained slides of 953 CRC patients, diagnosed between 1997 and 2007 were evaluated for tumour budding according to the ITBCC-criteria. The tumour microenvironment was evaluated using tumour stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumour inflammatory cell infiltrate. Differential gene expression was assessed using TempO-Seq gene expression profiling (BioSpyder Technologies Inc., CA, USA) using the Surrogate+Tox targeted panel (2,733 genes selected for biological diversity, maximal information content, and widespread pathway coverage). Results: High budding (n = 269/ 28%) was significantly associated with TNM stage (P < 0.001), venous invasion (P < 0.001), weak KM grade (P < 0.001), high TSP (P < 0.001) and reduced cancer specific survival (CSS) (HR = 5.04; 95% confidence interval [CI], 3.50-9.51; P < 0.001) and was independent of venous invasion, KM grade, and Ki67 proliferation index. RNA expression analysis was employed using TempO-Seq to determine differential gene expression between tumours with (n = 8) and without budding (n = 18). Three genes were identified as significantly differentially expressed: S100A2 (S100 calcium binding protein A2) was upregulated by 2.9 fold (padj < 0.00001); REG1A (regenerating family member 1 alpha) was downregulated by 4.7 fold (padj < 0.01) and LCN2 (lipocalin 2) was downregulated by 2.2 fold (padj < 0.01). Conclusions: Tumour budding stratifies patients’ survival in primary operable colorectal cancer and associates with differing gene expression profiles and factors of the tumour. Therefore, the ITBCC budding evaluation method should be used to assess tumour budding as supplement the TNM staging system and can help to further subdivide colorectal cancer into new prognostic groups.

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