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Article: Metaproteomic Profile of the Colonic Luminal Microbiota From Patients With Colon Cancer.

Tanca, Alessandro / Abbondio, Marcello / Fiorito, Giovanni / Pira, Giovanna / Sau, Rosangela / Manca, Alessandra / Muroni, Maria Rosaria / Porcu, Alberto / Scanu, Antonio Mario / Cossu-Rocca, Paolo / De Miglio, Maria Rosaria / Uzzau, Sergio

Frontiers in microbiology

2022 Volume 13, Page(s) 869523

Abstract: Recent studies have provided evidence of interactions among the gut microbiota (GM), local host immune cells, and intestinal tissues in colon carcinogenesis. However, little is known regarding the functions exerted by the GM in colon cancer (CC), ... ...

Abstract	Recent studies have provided evidence of interactions among the gut microbiota (GM), local host immune cells, and intestinal tissues in colon carcinogenesis. However, little is known regarding the functions exerted by the GM in colon cancer (CC), particularly with respect to tumor clinical classification and lymphocyte infiltration. In addition, stool, usually employed as a proxy of the GM, cannot fully represent the original complexity of CC microenvironment. Here, we present a pilot study aimed at characterizing the metaproteome of CC-associated colonic luminal contents and identifying its possible associations with CC clinicopathological features. Colonic luminal contents were collected from 24 CC tissue specimens immediately after surgery. Samples were analyzed by shotgun metaproteomics. Almost 30,000 microbial peptides were quantified in the samples, enabling the achievement of the taxonomic and functional profile of the tumor-associated colonic luminal metaproteome. Upon sample aggregation based on tumor stage, grade, or tumor-infiltrating lymphocytes (TILs), peptide sets enabling discrimination of sample groups were identified through discriminant analysis (DA). As a result,
Language	English
Publishing date	2022-04-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2022.869523
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Article ; Online: Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers, Signaling Pathways and miRNAome.

Angius, Andrea / Scanu, Antonio Mario / Arru, Caterina / Muroni, Maria Rosaria / Rallo, Vincenzo / Deiana, Giulia / Ninniri, Maria Chiara / Carru, Ciriaco / Porcu, Alberto / Pira, Giovanna / Uva, Paolo / Cossu-Rocca, Paolo / De Miglio, Maria Rosaria

International journal of molecular sciences

2021 Volume 22, Issue 4

Abstract: Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small ... ...

Abstract	Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of CCSCs, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.
MeSH term(s)	Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Disease Progression ; Epithelial-Mesenchymal Transition/genetics ; Epithelial-Mesenchymal Transition/physiology ; Feedback, Physiological ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Models, Biological ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Signal Transduction
Chemical Substances	Biomarkers, Tumor ; MicroRNAs
Language	English
Publishing date	2021-02-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22041603
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Article: Molecular Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 Isolates From Central Inner Sardinia.

Malune, Paolo / Piras, Giovanna / Monne, Maria / Fiamma, Maura / Asproni, Rosanna / Fancello, Tatiana / Manai, Antonio / Carta, Franco / Pira, Giovanna / Fancello, Patrizia / Rosu, Valentina / Uras, Antonella / Mereu, Caterina / Mameli, Giuseppe / Lo Maglio, Iana / Garau, Maria Cristina / Palmas, Angelo Domenico

Frontiers in microbiology

2022 Volume 12, Page(s) 827799

Abstract: Background: The SARS-CoV-2 pandemic stimulated an outstanding global sequencing effort, which allowed to monitor viral circulation and evolution. Nuoro province (Sardinia, Italy), characterized by a relatively isolated geographical location and a low ... ...

Abstract	Background: The SARS-CoV-2 pandemic stimulated an outstanding global sequencing effort, which allowed to monitor viral circulation and evolution. Nuoro province (Sardinia, Italy), characterized by a relatively isolated geographical location and a low population density, was severely hit and displayed a high incidence of infection. Methods: Amplicon approach Next Generation Sequencing and subsequent variant calling in 92 respiratory samples from SARS-CoV-2 infected patients involved in infection clusters from March 2020 to May 2021. Results: Phylogenetic analysis displayed a coherent distribution of sequences in terms of lineage and temporal evolution of pandemic. Circulating lineage/clade characterization highlighted a growing diversity over time, with an increasingly growing number of mutations and variability of spike and nucleocapsid proteins, while viral RdRp appeared to be more conserved. A total of 384 different mutations were detected, of which 196 were missense and 147 synonymous ones. Mapping mutations along the viral genome showed an irregular distribution in key genes. Conclusion: The analysis of the 92 viral genome highlighted evolution over time and identified which mutations are more widespread than others. The high number of sequences also permits the identification of subclusters that are characterized by subtle differences, not only in terms of lineage, which may be used to reconstruct transmission clusters. The disclosure of viral genetic diversity and timely identification of new variants is a useful tool to guide public health intervention measures.
Language	English
Publishing date	2022-01-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2021.827799
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Article ; Online: Impact on breast cancer susceptibility and clinicopathological traits of common genetic polymorphisms in

Floris, Matteo / Pira, Giovanna / Castiglia, Paolo / Idda, Maria Laura / Steri, Maristella / De Miglio, Maria Rosaria / Piana, Andrea / Cossu, Andrea / Azara, Antonio / Arru, Caterina / Deiana, Giovanna / Putzu, Carlo / Sanna, Valeria / Carru, Ciriaco / Serra, Antonello / Bisail, Marco / Muroni, Maria Rosaria

Oncology letters

2022 Volume 24, Issue 4, Page(s) 331

Abstract: Common variants of genes involved in DNA damage correction [tumor protein p53 ( ...

Abstract	Common variants of genes involved in DNA damage correction [tumor protein p53 (
Language	English
Publishing date	2022-08-08
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2573196-8
ISSN	1792-1082 ; 1792-1074
ISSN (online)	1792-1082
ISSN	1792-1074
DOI	10.3892/ol.2022.13451
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Article ; Online: Deciphering clinical significance of BCL11A isoforms and protein expression roles in triple-negative breast cancer subtype.

Angius, Andrea / Pira, Giovanna / Cossu-Rocca, Paolo / Sotgiu, Giovanni / Saderi, Laura / Muroni, Maria Rosaria / Virdis, Patrizia / Piras, Daniela / Vincenzo, Rallo / Carru, Ciriaco / Coradduzza, Donatella / Uras, Maria Gabriela / Cottu, Pierina / Fancellu, Alessandro / Orrù, Sandra / Uva, Paolo / De Miglio, Maria Rosaria

Journal of cancer research and clinical oncology

2022 Volume 149, Issue 7, Page(s) 3951–3963

Abstract: Purpose: Triple negative breast cancer (TNBC) is an aggressive clinical tumor, accounting for about 25% of breast cancer (BC) related deaths. Chemotherapy is the only therapeutic option to treat TNBC, hence a detailed understanding of the biology and ... ...

Abstract	Purpose: Triple negative breast cancer (TNBC) is an aggressive clinical tumor, accounting for about 25% of breast cancer (BC) related deaths. Chemotherapy is the only therapeutic option to treat TNBC, hence a detailed understanding of the biology and its categorization is required. To investigate the clinical relevance of BCL11A in TNBC subtype, we focused on gene and protein expression and its mutational status in a large cohort of this molecular subtype. Methods: Gene expression profiling of BCL11A and its isoforms (BCL11A-XL, BCL11A-L and BCL11A-S) has been determined in Luminal A, Luminal B, HER2-enriched and TNBC subtypes. BCL11A protein expression has been analyzed by immunohistochemistry (IHC) and its mutational status by Sanger sequencing. Results: In our study, BCL11A was significantly overexpressed in TNBC both at transcriptional and translational levels compared to other BC molecular subtypes. A total of 404 TNBCs were selected and examined showing a high prevalence of BCL11A-XL (37.3%) and BCL11A-L (31.4%) isoform expression in TNBC, associated with a 26% of BCL11A protein expression levels. BCL11A protein expression predicts scarce LIV (HR = 0.52; 95% CI, 0.29-0.92, P = 0.03) and AR downregulation (HR = 0.37; 95% CI, 0.16-0.88; P = 0.02), as well as a higher proliferative index in TNBC cells. BCL11A-L expression is associated with more aggressive TNBC histological types, such as medullary and metaplastic carcinoma. Conclusion: Our finding showed that BCL11A protein expression acts as an unfavorable prognostic factor in TNBC patients, especially in non luminal TNBCs subgroups. These results may yield a better treatment strategy by providing a new parameter for TNBC classification.
MeSH term(s)	Humans ; Female ; Triple Negative Breast Neoplasms/pathology ; Breast Neoplasms/pathology ; Clinical Relevance ; Breast/pathology ; Transcription Factors ; Immunohistochemistry ; Prognosis ; Repressor Proteins/genetics
Chemical Substances	Transcription Factors ; BCL11A protein, human ; Repressor Proteins
Language	English
Publishing date	2022-08-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-022-04301-w
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Article: Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype.

Angius, Andrea / Cossu-Rocca, Paolo / Arru, Caterina / Muroni, Maria Rosaria / Rallo, Vincenzo / Carru, Ciriaco / Uva, Paolo / Pira, Giovanna / Orrù, Sandra / De Miglio, Maria Rosaria

Cancers

2020 Volume 12, Issue 11

Abstract: Development of new research, classification, and therapeutic options are urgently required due to the fact that TNBC is a heterogeneous malignancy. The expression of high molecular weight cytokeratins identifies a biologically and clinically distinct ... ...

Abstract	Development of new research, classification, and therapeutic options are urgently required due to the fact that TNBC is a heterogeneous malignancy. The expression of high molecular weight cytokeratins identifies a biologically and clinically distinct subgroup of TNBCs with a basal-like phenotype, representing about 75% of TNBCs, while the remaining 25% includes all other intrinsic subtypes. The triple negative phenotype in basal-like breast cancer (BLBC) makes it unresponsive to endocrine therapy, i.e., tamoxifen, aromatase inhibitors, and/or anti-HER2-targeted therapies; for this reason, only chemotherapy can be considered an approach available for systemic treatment even if it shows poor prognosis. Therefore, treatment for these subgroups of patients is a strong challenge for oncologists due to disease heterogeneity and the absence of unambiguous molecular targets. Dysregulation of the cellular miRNAome has been related to huge cellular process deregulations underlying human malignancy. Consequently, epigenetics is a field of great promise in cancer research. Increasing evidence suggests that specific miRNA clusters/signatures might be of clinical utility in TNBCs with basal-like phenotype. The epigenetic mechanisms behind tumorigenesis enable progress in the treatment, diagnosis, and prevention of cancer. This review intends to summarize the epigenetic findings related to miRNAome in TNBCs with basal-like phenotype.
Language	English
Publishing date	2020-11-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12113298
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Article ; Online: Fecal Microbiota Signatures in Celiac Disease Patients With Poly-Autoimmunity.

Bibbò, Stefano / Abbondio, Marcello / Sau, Rosangela / Tanca, Alessandro / Pira, Giovanna / Errigo, Alessandra / Manetti, Roberto / Pes, Giovanni Mario / Dore, Maria Pina / Uzzau, Sergio

Frontiers in cellular and infection microbiology

2020 Volume 10, Page(s) 349

Abstract: To date, reliable tests enabling the identification of celiac disease (CD) patients at a greater risk of developing poly-autoimmune diseases are not yet available. We therefore aimed to identify non-invasive microbial biomarkers, useful to implement ... ...

Abstract	To date, reliable tests enabling the identification of celiac disease (CD) patients at a greater risk of developing poly-autoimmune diseases are not yet available. We therefore aimed to identify non-invasive microbial biomarkers, useful to implement diagnosis of poly-autoimmunity. Twenty CD patients with poly-autoimmunity (cases) and 30 matched subjects affected exclusively by CD (controls) were selected. All patients followed a varied gluten-free diet for at least 1 year. Fecal microbiota composition was characterized using bacterial 16S ribosomal RNA gene sequencing. Significant differences in gut microbiota composition between CD patients with and without poly-autoimmune disease were found using the edgeR algorithm. Spearman correlations between gut microbiota and clinical, demographic, and anthropometric data were also examined. A significant reduction of
MeSH term(s)	Autoimmune Diseases ; Autoimmunity ; Celiac Disease ; Feces ; Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S/genetics
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2020-07-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2020.00349
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Article ; Online: Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in breast cancer: a Sardinian preliminary case-control study.

Castiglia, Paolo / Sanna, Valeria / Azara, Antonio / De Miglio, Maria R / Murgia, Luciano / Pira, Giovanna / Sanges, Francesca / Fancellu, Alessandro / Carru, Ciriaco / Bisail, Marco / Muroni, Maria Rosaria

International journal of medical sciences

2019 Volume 16, Issue 8, Page(s) 1089–1095

Abstract: Two common polymorphisms in the MTHFR gene, C677T and A1298C, are associated with reduced enzyme activity and may be associated with breast cancer susceptibility. We performed a case-control study to investigate the association between the two SNPs in ... ...

Abstract	Two common polymorphisms in the MTHFR gene, C677T and A1298C, are associated with reduced enzyme activity and may be associated with breast cancer susceptibility. We performed a case-control study to investigate the association between the two SNPs in the MTHFR gene and risk of breast cancer. In total, 58 breast cancer patients and 58 unaffected controls were enrolled in the study. Polymerase chain reaction/restriction fragment length polymorphism technique (PCR-RFLP) was conducted to determine the genotypes. No significant differences were found in the genotypes of the two polymorphisms of the MTHFR gene between cases and controls. The OR and 95% CI for the 677CC, 677CT and 677TT genotypes were 1.00, 0.95 (0.39-2.31) and 0.87 (0.27-2.80), respectively; those of the 1298AA, 1298AC and 1298CC genotypes were 1.00, 0.59 (0.26-1.36) and 0.78 (1.32-4.66) respectively. Furthermore, it has been shown in patients with breast cancer a risk of presenting with an aggressive biophenotype about twice or three times higher in the presence of the C677T and A1298C polymorphisms, respectively. Finally, the A1298Cpolymorphism is significantly associated with increased recurrence risk of lymph node-positive breast cancer. Our study has not shown a significant association between MTHFR gene polymorphisms and breast cancer risk. However, it highlighted the key-role played by the presence of mutant alleles for both polymorphisms in increasing the risk of developing more aggressive phenotypes; moreover, specifically in A1298C, it might also lead to a higher risk of developing lymph node metastasis.
MeSH term(s)	Adult ; Aged ; Body Mass Index ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Humans ; Italy ; Lymphatic Metastasis/genetics ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Middle Aged ; Polymorphism, Single Nucleotide
Chemical Substances	MTHFR protein, human (EC 1.5.1.20) ; Methylenetetrahydrofolate Reductase (NADPH2) (EC 1.5.1.20)
Language	English
Publishing date	2019-07-22
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2151424-0
ISSN	1449-1907 ; 1449-1907
ISSN (online)	1449-1907
ISSN	1449-1907
DOI	10.7150/ijms.32162
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Article ; Online: Multiple Signatures of the JC Polyomavirus in Paired Normal and Altered Colorectal Mucosa Indicate a Link with Human Colorectal Cancer, but Not with Cancer Progression.

Uleri, Elena / Piu, Claudia / Caocci, Maurizio / Ibba, Gabriele / Sanges, Francesca / Pira, Giovanna / Murgia, Luciano / Barmina, Michele / Giannecchini, Simone / Porcu, Alberto / Serra, Caterina / Scanu, Antonio M / De Miglio, Maria R / Dolei, Antonina

International journal of molecular sciences

2019 Volume 20, Issue 23

Abstract: The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, ... ...

Abstract	The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient's cohorts, and methods. Studies of simultaneous detection, quantification, and characterization of JCV presence/expression in paired samples of normal/altered tissues of the same patient are lacking. Therefore, we simultaneously quantified JCV presence (DNA) and expression (mRNA and protein) of T-antigen (
MeSH term(s)	Adenocarcinoma/metabolism ; Adenocarcinoma/pathology ; Adenocarcinoma/virology ; Adenoma/metabolism ; Adenoma/pathology ; Adenoma/virology ; Aged ; Antigens, Viral, Tumor/metabolism ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Colonic Neoplasms/virology ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/virology ; DNA, Viral/genetics ; Disease Progression ; Female ; Humans ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Intestinal Mucosa/virology ; JC Virus/pathogenicity ; Male ; Middle Aged ; Polyomavirus Infections/metabolism ; Polyomavirus Infections/pathology ; Polyomavirus Infections/virology ; Tumor Virus Infections/metabolism ; Tumor Virus Infections/pathology ; Tumor Virus Infections/virology
Chemical Substances	Antigens, Viral, Tumor ; DNA, Viral
Language	English
Publishing date	2019-11-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20235965
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Article ; Online: Landscape of transcriptome variations uncovering known and novel driver events in colorectal carcinoma.

Pira, Giovanna / Uva, Paolo / Scanu, Antonio Mario / Rocca, Paolo Cossu / Murgia, Luciano / Uleri, Elena / Piu, Claudia / Porcu, Alberto / Carru, Ciriaco / Manca, Alessandra / Persico, Ivana / Muroni, Maria Rosaria / Sanges, Francesca / Serra, Caterina / Dolei, Antonia / Angius, Andrea / De Miglio, Maria Rosaria

Scientific reports

2020 Volume 10, Issue 1, Page(s) 432

Abstract: We focused on an integrated view of genomic changes in Colorectal cancer (CRC) and distant normal colon tissue (NTC) to test the effectiveness of expression profiling on identification of molecular targets. We performed transcriptome on 16 primary ... ...

Abstract	We focused on an integrated view of genomic changes in Colorectal cancer (CRC) and distant normal colon tissue (NTC) to test the effectiveness of expression profiling on identification of molecular targets. We performed transcriptome on 16 primary coupled CRC and NTC tissues. We identified pathways and networks related to pathophysiology of CRC and selected potential therapeutic targets. CRC cells have multiple ways to reprogram its transcriptome: a functional enrichment analysis in 285 genes, 25% mutated, showed that they control the major cellular processes known to promote tumorigenesis. Among the genes showing alternative splicing, cell cycle related genes were upregulated (CCND1, CDC25B, MCM2, MCM3), while genes involved in fatty acid metabolism (ACAAA2, ACADS, ACAT1, ACOX, CPT1A, HMGCS2) were downregulated. Overall 148 genes showed differential splicing identifying 17 new isoforms. Most of them are involved in the pathogenesis of CRC, although the functions of these variants remain unknown. We identified 2 in-frame fusion events, KRT19-KRT18 and EEF1A1-HSP90AB1, encoding for chemical proteins in two CRC patients. We draw a functional interactome map involving integrated multiple genomic features in CRC. Finally, we underline that two functional cell programs are prevalently deregulated and absolutely crucial to determinate and sustain CRC phenotype.
MeSH term(s)	Aged ; Aged, 80 and over ; Alternative Splicing ; Base Sequence ; Colon/cytology ; Colon/metabolism ; Colon/pathology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Female ; Gene Expression Profiling ; Genomics ; Humans ; Male ; Middle Aged ; Mutation ; RNA-Seq
Language	English
Publishing date	2020-01-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-57311-z
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