Kajsa Björner, Wei-Na Chen, Venkata Ram Gannavarapu, Fredrik Axling, Miklos Gulyas, Mohammad Abdul Halim, Dominic-Luc Webb, Per M Hellström
{"title":"高iNOS和IL-1β免疫反应是结肠炎相关结直肠癌肿瘤的特征,但不能预测5年生存率。","authors":"Kajsa Björner, Wei-Na Chen, Venkata Ram Gannavarapu, Fredrik Axling, Miklos Gulyas, Mohammad Abdul Halim, Dominic-Luc Webb, Per M Hellström","doi":"10.48101/ujms.v128.10241","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD; mainly ulcerative colitis and Crohn's disease) is associated with the development of colorectal cancer (CRC) referred to as colitis-associated colorectal cancer (CAC). In inflammatory flares of IBD, the production of luminal nitric oxide (NO) increases due to the increased inducible nitric oxide synthase (iNOS) activity in inflamed tissue. It is believed that iNOS parallels pro-inflammatory interleukin-1β (IL-1β). How these biomarkers relate to CAC pathogenesis or survival is unknown.</p><p><strong>Aim: </strong>The primary aim of this study was to investigate iNOS and IL-1β immunoreactivity in CAC tumors in comparison with CRC and normal colonic mucosa, and the secondary aim was to determine if immunoreactivity correlates with 5-year survival of CAC.</p><p><strong>Methods: </strong>Immunohistochemistry was performed on tissue sections as follows: CAC (<i>n</i> = 59); sporadic CRC (sCRC) (<i>n</i> = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) (<i>n =</i> 22); paracancerous IBD (pIBD) (<i>n =</i> 12). The expression of iNOS and IL-1β was quantified separately for epithelium and stroma. Data were evaluated using the Mann-Whitney U-test and the log-rank test for 5-year Kaplan-Meier survival curves. Results were compared with online mRNA databases.</p><p><strong>Results: </strong>Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS (<i>P</i> < 0.01) and IL-1β (<i>P</i> < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa (<i>P</i> < 0.001), whereas IL-1β was higher (<i>P</i> < 0.05). Immunoreactivity differences of iNOS or IL-1β among CAC patients failed to correlate with 5-year survival. These findings were supported by online mRNA databases.</p><p><strong>Conclusion: </strong>Consistent with high NO production in IBD, there is more iNOS in CAC epithelium, albeit not in stroma. This immunoreactivity difference exists for IL-1β in both epithelium and stroma. The intervention of arginine or iNOS activity for CAC chemotherapy is not straightforward.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"28 ","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10770641/pdf/","citationCount":"0","resultStr":"{\"title\":\"High iNOS and IL-1β immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival.\",\"authors\":\"Kajsa Björner, Wei-Na Chen, Venkata Ram Gannavarapu, Fredrik Axling, Miklos Gulyas, Mohammad Abdul Halim, Dominic-Luc Webb, Per M Hellström\",\"doi\":\"10.48101/ujms.v128.10241\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Inflammatory bowel disease (IBD; mainly ulcerative colitis and Crohn's disease) is associated with the development of colorectal cancer (CRC) referred to as colitis-associated colorectal cancer (CAC). In inflammatory flares of IBD, the production of luminal nitric oxide (NO) increases due to the increased inducible nitric oxide synthase (iNOS) activity in inflamed tissue. It is believed that iNOS parallels pro-inflammatory interleukin-1β (IL-1β). How these biomarkers relate to CAC pathogenesis or survival is unknown.</p><p><strong>Aim: </strong>The primary aim of this study was to investigate iNOS and IL-1β immunoreactivity in CAC tumors in comparison with CRC and normal colonic mucosa, and the secondary aim was to determine if immunoreactivity correlates with 5-year survival of CAC.</p><p><strong>Methods: </strong>Immunohistochemistry was performed on tissue sections as follows: CAC (<i>n</i> = 59); sporadic CRC (sCRC) (<i>n</i> = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) (<i>n =</i> 22); paracancerous IBD (pIBD) (<i>n =</i> 12). The expression of iNOS and IL-1β was quantified separately for epithelium and stroma. Data were evaluated using the Mann-Whitney U-test and the log-rank test for 5-year Kaplan-Meier survival curves. Results were compared with online mRNA databases.</p><p><strong>Results: </strong>Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS (<i>P</i> < 0.01) and IL-1β (<i>P</i> < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa (<i>P</i> < 0.001), whereas IL-1β was higher (<i>P</i> < 0.05). Immunoreactivity differences of iNOS or IL-1β among CAC patients failed to correlate with 5-year survival. These findings were supported by online mRNA databases.</p><p><strong>Conclusion: </strong>Consistent with high NO production in IBD, there is more iNOS in CAC epithelium, albeit not in stroma. This immunoreactivity difference exists for IL-1β in both epithelium and stroma. The intervention of arginine or iNOS activity for CAC chemotherapy is not straightforward.</p>\",\"PeriodicalId\":23458,\"journal\":{\"name\":\"Upsala journal of medical sciences\",\"volume\":\"28 \",\"pages\":\"\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-01-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10770641/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Upsala journal of medical sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.48101/ujms.v128.10241\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Upsala journal of medical sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.48101/ujms.v128.10241","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
High iNOS and IL-1β immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival.
Background: Inflammatory bowel disease (IBD; mainly ulcerative colitis and Crohn's disease) is associated with the development of colorectal cancer (CRC) referred to as colitis-associated colorectal cancer (CAC). In inflammatory flares of IBD, the production of luminal nitric oxide (NO) increases due to the increased inducible nitric oxide synthase (iNOS) activity in inflamed tissue. It is believed that iNOS parallels pro-inflammatory interleukin-1β (IL-1β). How these biomarkers relate to CAC pathogenesis or survival is unknown.
Aim: The primary aim of this study was to investigate iNOS and IL-1β immunoreactivity in CAC tumors in comparison with CRC and normal colonic mucosa, and the secondary aim was to determine if immunoreactivity correlates with 5-year survival of CAC.
Methods: Immunohistochemistry was performed on tissue sections as follows: CAC (n = 59); sporadic CRC (sCRC) (n = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) (n = 22); paracancerous IBD (pIBD) (n = 12). The expression of iNOS and IL-1β was quantified separately for epithelium and stroma. Data were evaluated using the Mann-Whitney U-test and the log-rank test for 5-year Kaplan-Meier survival curves. Results were compared with online mRNA databases.
Results: Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS (P < 0.01) and IL-1β (P < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa (P < 0.001), whereas IL-1β was higher (P < 0.05). Immunoreactivity differences of iNOS or IL-1β among CAC patients failed to correlate with 5-year survival. These findings were supported by online mRNA databases.
Conclusion: Consistent with high NO production in IBD, there is more iNOS in CAC epithelium, albeit not in stroma. This immunoreactivity difference exists for IL-1β in both epithelium and stroma. The intervention of arginine or iNOS activity for CAC chemotherapy is not straightforward.
期刊介绍:
Upsala Journal of Medical Sciences is published for the Upsala Medical Society. It has been published since 1865 and is one of the oldest medical journals in Sweden.
The journal publishes clinical and experimental original works in the medical field. Although focusing on regional issues, the journal always welcomes contributions from outside Sweden.
Specially extended issues are published occasionally, dealing with special topics, congress proceedings and academic dissertations.