| 1. |
- Ling, Agnes, 1976-, et al.
(författare)
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TAP1 down-regulation elicits immune escape and poor prognosis in colorectal cancer
- 2017
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Ingår i: Oncoimmunology. - 2162-4011 .- 2162-402X. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- The anti-tumor immune response has been shown to be of great prognostic importance in colorectal cancer (CRC) and so has the tumors ability for immune evasion. Our aim of this study was to investigate tumor factors that influence immunity. We used a gene expression array to search for potential mechanisms of tumor immune escape. One candidate gene identified was TAP1, involved in antigen presentation by MHC class I. TAP1 protein expression was evaluated by immunohistochemistry in 436 CRC patients of the Colorectal Cancer in Umeå Study cohort. We found a significant association between a downregulated expression of TAP1 and low infiltration of various subtypes of lymphocytes as well as macrophages. A downregulated expression of TAP1 was further found to be independent of molecular characteristics, suggesting TAP1 down-regulation to reach beyond the well described highly immunogenic MSI CRCs. A low expression of TAP1 was also significantly associated with poor prognosis in patients with CRC, a result that stayed significant in tumor front of early stage tumors (stage I-II) through multivariable analyses. Furthermore, we found that TAP1 expression was inversely correlated with methylation at sites in close proximity to the promoter region. In summary, our results show down-regulation of TAP1 to be a general mechanism of tumor immune escape in CRC and a poor prognostic factor in stage I-II CRC patients. We also suggest that methylation of the TAP1 gene may be a putative mechanism for TAP1 downregulation.
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| 2. |
- Rutegård, Martin, et al.
(författare)
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Efficiency of Colorectal Cancer Surveillance in Patients With Ulcerative Colitis : 38 Years' Experience in a Patient Cohort From a Defined Population Area
- 2017
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Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 106:2, s. 133-138
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Ulcerative colitis increases the risk of developing colorectal cancer. Colonoscopic surveillance is recommended although there are no randomized trials evaluating the efficacy of such a strategy. This study is an update of earlier studies from an ongoing colonoscopic surveillance program.MATERIAL AND METHODS: All patients with ulcerative colitis were invited to the surveillance program that started in 1977 at Örnsköldsvik Hospital, located in the northern part of Sweden. Five principal endoscopists performed the colonoscopies and harvested mucosal sampling for histopathological evaluation. Some 323 patients from the defined catchment area were studied from 1977 to 2014. At the end of the study period, 130 patients, including those operated on, had had total colitis for more than 10 years.RESULTS: In total, 1481 colonoscopies were performed on 323 patients during the study period without any major complications. In all, 10 cases of colorectal cancer were diagnosed in 9 patients, of whom 1 died from colorectal cancer. The cumulative incidence of colorectal cancer was 1.4% at 10 years, 2.0% at 20 years, 3.0% at 30 years, and 9.4% at 40 years of disease duration, respectively. The standardized colorectal cancer incidence ratio was 3.01 (95% confidence interval: 1.42-5.91). Major surgery was performed on 65 patients; for 20 of these, the indication for surgery was dysplasia or colorectal cancer. Panproctocolectomy was performed in 43 patients.CONCLUSION: This study supports that colonoscopic surveillance is a safe and effective long-term measure to detect dysplasia and progression to cancer. The low numbers of colorectal cancer-related deaths in our study suggest that early detection of neoplasia and adequate surgical intervention within a surveillance program may reduce colorectal cancer mortality in ulcerative colitis patients.
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| 3. |
- Svenson, Ulrika, et al.
(författare)
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Telomere length in peripheral leukocytes is associated with immune cell tumor infiltration and prognosis in colorectal cancer patients
- 2016
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 37:8, s. 10877-10882
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Tidskriftsartikel (refereegranskat)abstract
- Telomeres are protective structures at the end of chromosomes, essential for chromosomal integrity. A large number of studies have investigated leukocyte telomere length as a possible risk marker for various cancers, colorectal cancer (CRC) included. In contrast, studies investigating leukocyte telomere length in relation to CRC survival are lacking. We previously reported that relative telomere length (RTL) of leukocytes collected at diagnosis predicted survival in patients with breast and kidney cancer. We suggested that these findings might reflect various immunological mechanisms, affected by the presence of a tumor. In the present study, leukocyte RTL was examined in relation to immune cell tumor infiltration and prognosis in 130 patients with CRC diagnosis. RTL was measured with a well-established qPCR method. We found that patients with the highest degree of lymphocyte tumor infiltration had shorter leukocyte RTL. Consistent with our previous findings, short RTL was a favorable prognostic marker in univariate survival analysis. In the current study, RTL did not remain as an independent predictor in multivariate survival analysis, when including metastatic status in the model. However, a non-significant trend towards a similar telomere-associated survival pattern was observed in patients with limited disease. In contrast, for patients who died of other causes than CRC, short RTL was associated with significantly shorter survival time. To our knowledge, this is the first study to investigate an association between leukocyte RTL, immune cell tumor infiltration, and cancer-specific survival in CRC patients. Larger studies are warranted to verify these findings.
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