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Hammarström, Sten
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Publications (10 of 69) Show all publications
Hammarström, S. (2019). Biomarker mRNAs as prognostic tools for lymph node analysis in colorectal cancer. Biomarkers in Medicine, 13(10), 801-803
Open this publication in new window or tab >>Biomarker mRNAs as prognostic tools for lymph node analysis in colorectal cancer
2019 (English)In: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 13, no 10, p. 801-803Article in journal, Editorial material (Other academic) Published
Keywords
lymphnode analysis, mRNA expression levels, selection of multiple biomarkers, tumor aggressiveness, tumor cell load
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-162680 (URN)10.2217/bmm-2019-0203 (DOI)000478997900001 ()31240946 (PubMedID)
Available from: 2019-09-02 Created: 2019-09-02 Last updated: 2019-09-02Bibliographically approved
AbdelMageed, M., Ali, H., Ohlsson, L., Lindmark, G., Hammarström, M.-L., Hammarström, S. & Sitohy, B. (2019). The Chemokine CXCL16 Is a New Biomarker for Lymph Node Analysis of Colon Cancer Outcome. International Journal of Molecular Sciences, 20(22), Article ID 5793.
Open this publication in new window or tab >>The Chemokine CXCL16 Is a New Biomarker for Lymph Node Analysis of Colon Cancer Outcome
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2019 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 22, article id 5793Article in journal (Refereed) Published
Abstract [en]

hemokines are important in the development and progression of tumors. We investigated the expression of CXCL14 and CXCL16 in colon cancer. Expression of mRNA was assessed in primary tumors and lymph nodes and CXCL16 mRNA levels were correlated to patient’s survival. Protein expression was investigated by two-color immunofluorescence and immunomorphometry. CXCL14 and CXCL16 mRNA levels and protein expression were significantly higher in colon cancer primary tumors compared to apparently normal colon tissue. Positive cells were tumor cells, as revealed by anti-CEA and anti-EpCAM staining. CXCL16, but not CXCL14, mRNA levels were significantly higher in hematoxylin and eosin positive (H&E(+)) compared to H&E(−) colon cancer lymph nodes or control nodes (P < 0.0001). CXCL16 mRNA was expressed in 5/5 colon cancer cell lines while CXCL14 was expressed significantly in only one. Kaplan-Meier analysis revealed that colon cancer patients with lymph nodes expressing high or very high levels (7.2 and 11.4 copies/18S rRNA unit, respectively) of CXCL16 mRNA had a decreased mean survival time of 30 and 46 months at the 12-year follow-up (P = 0.04, P = 0.005, respectively). In conclusion, high expression of CXCL16 mRNA in regional lymph nodes of colon cancer patients is a sign of a poor prognosis.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
chemokines, CXCL17, CEA, EpCAM, qRT-PCR, immunohistochemistry, immunomorphometry
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-167031 (URN)10.3390/ijms20225793 (DOI)000502786800275 ()31752131 (PubMedID)
Funder
Swedish Research CouncilVästerbotten County Council
Available from: 2020-01-09 Created: 2020-01-09 Last updated: 2020-01-09Bibliographically approved
Rashad, Y., Olsson, L., Israelsson, A., Öberg, Å., Lindmark, G., Hammarström, M.-L., . . . Sitohy, B. (2018). Lymph node CXCL17 messenger RNA: A new prognostic biomarker for colon cancer. Tumor Biology, 40(9), Article ID 1010428318799251.
Open this publication in new window or tab >>Lymph node CXCL17 messenger RNA: A new prognostic biomarker for colon cancer
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2018 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 40, no 9, article id 1010428318799251Article in journal (Refereed) Published
Abstract [en]

Lymph node metastasis is the most important prognostic characteristic of colorectal cancer. Carcinoembryonic antigen messenger RNA was shown to detect tumor cells that have disseminated to lymph nodes of colorectal cancer patients and to be at least as good as the hematoxylin and eosin method to predict survival in colorectal cancer patients. CXCL17 was recently shown to be ectopically expressed in colon cancer tumors. Therefore, CXCL17 may serve as prognostic marker alone or in combination with carcinoembryonic antigen. CXCL17 and carcinoembryonic antigen messenger RNA levels were determined using quantitative reverse transcription polymerase chain reaction with RNA copy standard in 389 lymph nodes of 120 colon cancer patients (stages I–IV) and 67 lymph nodes of 12 control patients with inflammatory bowel disease as well as in 68 primary tumors and 30 normal colon tissue samples. Lymph nodes of colon cancer patients were analyzed for CXCL17 and carcinoembryonic antigen protein expression by immunohistochemistry. CXCL17 messenger RNA was expressed in primary tumors at high levels, while it was barely detected in normal colon tissue (p < 0.0001). Similarly, CXCL17 messenger RNA levels were significantly higher in hematoxylin- and eosin-positive (hematoxylin and eosin (+)) lymph nodes compared to hematoxylin- and eosin-negative nodes (p < 0.0001). CXCL17 messenger RNA levels were investigated in lymph nodes grouped according to carcinoembryonic antigen messenger RNA levels: low (–), intermediate (int), and high (+). CXCL17 messenger RNA levels were higher in the carcinoembryonic antigen (int) and carcinoembryonic antigen (+) groups compared to the carcinoembryonic antigen (−) group (p = 0.03 and p < 0.0001, respectively). In lymph nodes of stage III and IV patients, CXCL17 messenger RNA levels correlated with carcinoembryonic antigen messenger RNA levels (p < 0.0001, r = 0.56 and p = 0.0002, r = 0.66, respectively). Staining of consecutive lymph node sections for CXCL17 and carcinoembryonic antigen demonstrated that the same cells expressed both proteins. Altogether, these results indicate that CXCL17 in lymph nodes is expressed by tumor cells. Patients were grouped according to the CXCL17 mRNA levels in the highest lymph node with low levels (−) and high levels (+). CXCL17(+) CC patients showed 2.2 fold increased risk for recurrence (P = 0.03) and decreased mean disease-free survival time of 33 months compared to CXCL17(−) CC patients (P = 0.03). CXCL17(+) carcinoembryonic antigen (int) colon cancer patients showed increased risk for recurrence by 8.3 fold (p = 0.04) and decreased mean disease-free survival time of 46 months compared to CXCL17(−) carcinoembryonic antigen (int) colon cancer patient at follow-up after 12 years (p = 0.02). The presence of tumor cells expressing CXCL17 in regional lymph nodes is a sign of poor prognosis. Analysis of CXCL17 messenger RNA is particularly useful to detect less differentiated colon cancer tumors expressing relatively low carcinoembryonic antigen messenger RNA levels. Thus, CXCL17 messenger RNA in combination with carcinoembryonic antigen messenger RNA may be used as a complementary tool to the hematoxylin and eosin method for detection of poorly differentiated, aggressive tumors.

Place, publisher, year, edition, pages
Sage Publications, 2018
Keywords
CXCL17, carcinoembryonic antigen, cumulative survival curve, disseminated tumor cells, recurrence risk
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-159263 (URN)10.1177/1010428318799251 (DOI)30198422 (PubMedID)2-s2.0-85054132105 (Scopus ID)
Available from: 2019-05-23 Created: 2019-05-23 Last updated: 2019-06-14Bibliographically approved
Pietz, G., De, R., Hedberg, M., Sjöberg, V., Sandström, O., Hernell, O., . . . Hammarström, M.-L. (2017). Immunopathology of childhood celiac disease: Key role of intestinal epithelial cells. PLoS ONE, 12(9), Article ID e0185025.
Open this publication in new window or tab >>Immunopathology of childhood celiac disease: Key role of intestinal epithelial cells
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 9, article id e0185025Article in journal (Refereed) Published
Abstract [en]

BACKGROUND & AIMS: Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria.

METHODS: Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels. Two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers, were utilized to assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells.

RESULTS: More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were significantly upregulated in intestinal epithelial cells at active celiac disease. Of these genes, 70% were upregulated by interferon-γ via the IRF1 pathway. Most interestingly, IRF1 was also upregulated by celiac disease-associated bacteria. The NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes, was expressed in intestinal epithelial cells.

CONCLUSION: A key factor in the epithelial reaction in celiac disease appears to be over-expression of IRF1 that could be inherent and/or due to presence of undesirable microbes that act directly on IRF1. Dual activation of IRF1 and IRF1-regulated genes, both directly and via the interleukin-18 dependent inflammasome would drastically enhance the inflammatory response and lead to the pathological situation seen in active celiac disease.

National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-139860 (URN)10.1371/journal.pone.0185025 (DOI)000411339900076 ()28934294 (PubMedID)
Available from: 2017-09-25 Created: 2017-09-25 Last updated: 2018-06-09Bibliographically approved
Ohlsson, L., Hammarström, M.-L., Lindmark, G., Hammarström, S. & Sitohy, B. (2016). Ectopic expression of the chemokine CXCL17 in colon cancer cells. British Journal of Cancer, 114(6), 697-703
Open this publication in new window or tab >>Ectopic expression of the chemokine CXCL17 in colon cancer cells
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2016 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, no 6, p. 697-703Article in journal (Refereed) Published
Abstract [en]

Background: The novel chemokine CXCL17 acts as chemoattractant for monocytes, macrophages and dendritic cells. CXCL17 also has a role in angiogenesis of importance for tumour development. Methods: Expression of CXCL17, CXCL10, CXCL9 and CCL2 was assessed in primary colon cancer tumours, colon carcinoma cell lines and normal colon tissue at mRNA and protein levels by real-time qRT-PCR, immunohistochemistry, two-colour immunofluorescence and immunomorphometry. Results: CXCL17 mRNA was expressed at 8000 times higher levels in primary tumours than in normal colon (P<0.0001). CXCL17 protein was seen in 17.2% of cells in tumours as compared with 0.07% in normal colon (P = 0.0002). CXCL10, CXCL9 and CCL2 mRNAs were elevated in tumours but did not reach the levels of CXCL17. CXCL17 and CCL2 mRNA levels were significantly correlated in tumours. Concordant with the mRNA results, CXCL10-and CXCL9-positive cells were detected in tumour tissue, but at significantly lower numbers than CXCL17. Two-colour immunofluorescence and single-colour staining of consecutive sections for CXCL17 and the epithelial cell markers carcinoembryonic antigen and BerEP4 demonstrated that colon carcinoma tumour cells indeed expressed CXCL17. Conclusions: CXCL17 is ectopically expressed in primary colon cancer tumours. As CXCL17 enhances angiogenesis and attracts immune cells, its expression could be informative for prognosis in colon cancer patients.

Keywords
CXCL17, CXCL10, CXCL9, CCL2, colon cancer, prognosis, immunomorphometry, qRT-PCR
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-119285 (URN)10.1038/bjc.2016.4 (DOI)000372523500013 ()26889977 (PubMedID)
Available from: 2016-05-16 Created: 2016-04-15 Last updated: 2018-06-07Bibliographically approved
Sjöberg, V., Hollén, E., Pietz, G., Magnusson, K.-E., Fälth-Magnusson, K., Sundström, M., . . . Hammarström, M.-L. (2014). Noncontaminated dietary oats may hamper normalization of the intestinal immune status in childhood celiac disease. Clinical and Translational Gastroenterology, 5, Article ID e58.
Open this publication in new window or tab >>Noncontaminated dietary oats may hamper normalization of the intestinal immune status in childhood celiac disease
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2014 (English)In: Clinical and Translational Gastroenterology, ISSN 2155-384X, E-ISSN 2155-384X, Vol. 5, article id e58Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Life-long, strict gluten-free diet (GFD) is the only treatment for celiac disease (CD). Because there is still uncertainty regarding the safety of oats for CD patients, the aim was to investigate whether dietary oats influence the immune status of their intestinal mucosa.

METHODS: Paired small intestinal biopsies, before and after >11 months on a GFD, were collected from children with CD who were enrolled in a randomized, double-blind intervention trial to either of two diets: standard GFD (GFD-std; n=13) and noncontaminated oat-containing GFD (GFD-oats; n=15). Expression levels of mRNAs for 22 different immune effector molecules and tight junction proteins were determined by quantitative reverse transcriptase (RT)-PCR.

RESULTS: The number of mRNAs that remained elevated was higher in the GFD-oats group (P=0.05). In particular, mRNAs for the regulatory T cell (Treg) signature molecules interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1), the cytotoxicity-activating natural killer (NK) receptors KLRC2/NKG2C and KLRC3/NKG2E, and the tight junction protein claudin-4 remained elevated. Between the two groups, most significant differences were seen for claudin-4 (P=0.003) and KLRC3/NKG2E (P=0.04).

CONCLUSIONS: A substantial fraction of pediatric CD patients seem to not tolerate oats. In these patients, dietary oats influence the immune status of the intestinal mucosa with an mRNA profile suggesting presence of activated cytotoxic lymphocytes and Tregs and a stressed epithelium with affected tight junctions. Assessment of changes in levels of mRNA for claudin-4 and KLC3/NKG2E from onset to after a year on oats containing GFD shows promise to identify these CD patients.

National Category
Basic Medicine Pediatrics
Research subject
Immunology
Identifiers
urn:nbn:se:umu:diva-93052 (URN)10.1038/ctg.2014.9 (DOI)000355530800002 ()24964993 (PubMedID)2-s2.0-84903278030 (Scopus ID)
Available from: 2014-09-11 Created: 2014-09-11 Last updated: 2018-06-07Bibliographically approved
Sjöberg, V., Sandström, O., Hedberg, M., Hammarström, S., Hernell, O. & Hammarström, M.-L. (2013). Intestinal T-cell responses in celiac disease: impact of celiac disease associated bacteria. PLoS ONE, 8(1), e53414
Open this publication in new window or tab >>Intestinal T-cell responses in celiac disease: impact of celiac disease associated bacteria
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 1, p. e53414-Article in journal (Refereed) Published
Abstract [en]

A hallmark of active celiac disease (CD), an inflammatory small-bowel enteropathy caused by permanent intolerance to gluten, is cytokine production by intestinal T lymphocytes. Prerequisites for contracting CD are that the individual carries the MHC class II alleles HLA-DQ2 and/or HLA-DQ8 and is exposed to gluten in the diet. Dysbiosis in the resident microbiota has been suggested to be another risk factor for CD. In fact, rod shaped bacteria adhering to the small intestinal mucosa were frequently seen in patients with CD during the "Swedish CD epidemic" and bacterial candidates could later be isolated from patients born during the epidemic suggesting long-lasting changes in the gut microbiota. Interleukin-17A (IL-17A) plays a role in both inflammation and anti-bacterial responses. In active CD IL-17A was produced by both CD8(+) T cells (Tc17) and CD4(+) T cells (Th17), with intraepithelial Tc17 cells being the dominant producers. Gluten peptides as well as CD associated bacteria induced IL-17A responses in ex vivo challenged biopsies from patients with inactive CD. The IL-17A response was suppressed in patients born during the epidemic when a mixture of CD associated bacteria was added to gluten, while the reverse was the case in patients born after the epidemic. Under these conditions Th17 cells were the dominant producers. Thus Tc17 and Th17 responses to gluten and bacteria seem to pave the way for the chronic disease with interferon-γ-production by intraepithelial Tc1 cells and lamina propria Th1 cells. The CD associated bacteria and the dysbiosis they might cause in the resident microbiota may be a risk factor for CD either by directly influencing the immune responses in the mucosa or by enhancing inflammatory responses to gluten.

Place, publisher, year, edition, pages
PLoS, Public Library of Science, 2013
National Category
Pediatrics Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-64525 (URN)10.1371/journal.pone.0053414 (DOI)000313551500069 ()23326425 (PubMedID)
Available from: 2013-01-31 Created: 2013-01-31 Last updated: 2018-06-08Bibliographically approved
Hedberg, M. E., Israelsson, A., Moore, E. R. B., Svensson-Stadler, L., Wai, S. N., Pietz, G., . . . Hammarstrom, S. (2013). Prevotella jejuni sp nov., isolated from the small intestine of a child with coeliac disease. International Journal of Systematic and Evolutionary Microbiology, 63(11), 4218-4223
Open this publication in new window or tab >>Prevotella jejuni sp nov., isolated from the small intestine of a child with coeliac disease
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2013 (English)In: International Journal of Systematic and Evolutionary Microbiology, ISSN 1466-5026, E-ISSN 1466-5034, Vol. 63, no 11, p. 4218-4223Article in journal (Refereed) Published
Abstract [en]

Five obligately anaerobic, Gram-stain-negative, saccharolytic and proteolytic, non-spore-forming bacilli (strains CD3 :27, CD3 :28(T), CD3 :33, CD3 :32 and CD3 :34) are described. All five strains were isolated from the small intestine of a female child with coeliac disease. Cells of the five strains were short rods or coccoid cells with longer filamentous forms seen sporadically. The organisms produced acetic acid and succinic acid as major metabolic end products. Phylogenetic analysis based on comparative 16S rRNA gene sequence analysis revealed close relationships between CD3 : 27, CD3 :28(T) and CD3 :33, between CD3 :32 and Prevotella histicola CCUG 55407(T), and between CD3 :34 and Prevotella melaninogenica CCUG 4944B(T). Strains CD3 : 27, CD3 :28(T) and CD3 :33 were clearly different from all recognized species within the genus Prevotella and related most closely to but distinct from P. melaninogenica. Based on 16S rRNA, RNA polymerase) beta-subunit (rpoB) and 60 kDa chaperonin protein subunit (cpn60) gene sequencing, and phenotypic, chemical and biochemical properties, strains CD3 :27, CD3 :28(T) and CD3 :33 are considered to represent a novel species within the genus Prevotella, for which the name Prevotella jejuni sp. nov. is proposed. Strain CD3 : 28(T) (=CCUG 60371(T)=DSM 26989(T)) is the type strain of the proposed novel species. All five strains were able to form homologous aggregates, in which tube-like structures were connecting individual bacteria cells. The five strains were able to bind to human intestinal carcinoma cell lines at 37 degrees C.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-84790 (URN)10.1099/ijs.0.052647-0 (DOI)000328666600045 ()
Available from: 2014-01-28 Created: 2014-01-20 Last updated: 2018-06-08Bibliographically approved
Hedberg, M. E., Moore, E. R., Svensson-Stadler, L., Hörstedt, P., Baranov, V., Hernell, O., . . . Hammarström, M.-L. (2012). Lachnoanaerobaculum a new genus in Lachnospiraceae; characterization of Lachnoanaerobaculum umeaense gen. nov., sp. nov., isolated from human small intestine, Lachnoanaerobaculum orale gen. nov., sp. nov., isolated from saliva and reclassification of Eubacterium saburreum (Prevot) Holdeman and Moore 1970 as Lachnoanaerobaculum saburreum comb. nov.. International Journal of Systematic and Evolutionary Microbiology, 62(11), 2685-2690
Open this publication in new window or tab >>Lachnoanaerobaculum a new genus in Lachnospiraceae; characterization of Lachnoanaerobaculum umeaense gen. nov., sp. nov., isolated from human small intestine, Lachnoanaerobaculum orale gen. nov., sp. nov., isolated from saliva and reclassification of Eubacterium saburreum (Prevot) Holdeman and Moore 1970 as Lachnoanaerobaculum saburreum comb. nov.
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2012 (English)In: International Journal of Systematic and Evolutionary Microbiology, ISSN 1466-5026, E-ISSN 1466-5034, Vol. 62, no 11, p. 2685-2690Article in journal (Refereed) Published
Abstract [en]

Two new obligately anaerobic Gram-positive, saccharolytic and non-proteolytic spore-forming bacilli (strain CD3:22 and N1) are described. Strain CD3:22 was isolated from a biopsy of the small intestine of a child with celiac disease and strain N1 from the saliva of a healthy young man. The cells of both strains were observed to be filamentous with lengths of approximately 5 to >20 µm, some of them curving and with swellings. The novel organisms produced H2S, NH3, butyric acid and acetic acid as major metabolic end products. Phylogenetic analyses, based on comparative 16S rRNA gene sequencing, revealed close relationships (98 % sequence similarity) between the two isolates, as well as the type strain of Eubacterium saburreum CCUG 28089T and four other Lachnospiraceae bacterium/E. saburreum-like organisms. This group of bacteria were clearly different from any of the 19 known genera in the family Lachnospiraceae. While Eubacterium spp. are reported to be non-spore-forming, reanalysis of E. saburreum CCUG 28089T confirmed that the bacterium, indeed, is able to form spores. Based on 16S rRNA gene sequencing, phenotypic and biochemical properties, CD3:22 (CCUG 58757T) and N1 (CCUG 60305T) represent new species of a new and distinct genus, named Lachnoanaerobaculum, in the family Lachnospiraceae [within the order Clostridiales, class Clostridia, phylum Firmicutes]. Strain CD3:22 is the type strain of the type species, Lachnoanaerobaculum umeaense gen. nov., sp. nov., of the proposed new genus. Strain N1 is the type strain of the species, Lachnoanaerobaculum orale gen. nov., sp. nov. Moreover, E. saburreum CCUG 28089T is reclassified as Lachnoanaerobaculum saburreum comb. nov.

National Category
Microbiology
Identifiers
urn:nbn:se:umu:diva-51168 (URN)10.1099/ijs.0.033613-0 (DOI)22228654 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 222720Swedish Research Council
Available from: 2012-01-11 Created: 2012-01-11 Last updated: 2018-06-08Bibliographically approved
Ohlsson, L., Israelsson, A., Öberg, Å., Palmqvist, R., Stenlund, H., Hammarström, M.-L., . . . Lindmark, G. (2012). Lymph node CEA and MUC2 mRNA as useful predictors of outcome in colorectal cancer. International Journal of Cancer, 130(8), 1833-1843
Open this publication in new window or tab >>Lymph node CEA and MUC2 mRNA as useful predictors of outcome in colorectal cancer
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2012 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 130, no 8, p. 1833-1843Article in journal (Refereed) Published
Abstract [en]

The aim was to explore the utility for staging and prognostic impact of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20), guanylyl cyclase C (GCC), CUB domain protein 1 (CDCP1) and mucin 2 (MUC2) mRNA levels in mesenteric lymph nodes of colorectal cancer (CRC) patients. Lymph nodes were collected at surgery and bisected; one half was subjected to biomarker mRNA analysis using real-time quantitative RT-PCR and the other half to routine histopathology. Lymph nodes from 174 CRC patients and 24 controls were analyzed. The median follow-up time was 59 (range 17-131) months. Cut-off levels were defined by analyzing quintiles by Cox regression model. CEA mRNA showed the best discriminating power between patients with recurrence in CRC after surgery and patients who were apparently disease-free (P=0.015). The risk of recurrence for the CEA(+) patients was 4.6 times greater than for the CEA(-) patients (P<0.0001). The other biomarkers gave lower hazard ratios. Cumulative survival analysis demonstrated that the average survival time was 99 months for CEA(-) patients compared to 39 months for CEA(+) patients, a difference of 60 months (P<0.0001). Six to nine percent of the stage I and II patients [H&E(-)] had CEA(+), CK20(+), GCC(+) and/or MUC2(+) lymph nodes. Two of these patients died from recurrent CRC. Low lymph node MUC2/CEA mRNA ratio identified patients with high risk for recurrence (P=0.011). Thus, qRT-PCR of CEA mRNA is a sensitive method to identify tumor cells in lymph nodes of CRC patients and, in combination with MUC2 mRNA, allows improved prediction of clinical outcome. © 2011 Wiley-Liss, Inc.

Keywords
colorectal cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-49812 (URN)10.1002/ijc.26182 (DOI)21618511 (PubMedID)
Available from: 2011-11-18 Created: 2011-11-18 Last updated: 2018-06-08Bibliographically approved
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