Epithelial Human Leukocyte Antigen-DR Expression Predicts Reduced Recurrence Rates and Prolonged Survival in Rectal Cancer Patients

Bruin, Elza C. de; Velde, Cornelis J.H. van de; Krieken, J. Han J.M. van; Marijnen, Corrie A.M.; Medema, Jan Paul

doi:10.1158/1078-0432.ccr-07-1597

Cited by 22 publications

(16 citation statements)

References 36 publications

(29 reference statements)

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“…27 The transcription of MHC II genes is tightly regulated by CIITA in healthy B cells with dysregulation of CIITA observed in tumors. 18 Our results indicate that high CIITA expression is associated with an increased risk of death.…”

Section: Discussionmentioning

confidence: 99%

Role of Inflammatory Related Gene Expression in Clear Cell Renal Cell Carcinoma Development and Clinical Outcomes

Tan

Hildebrandt

et al. 2011

Journal of Urology

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Purpose Renal cell carcinoma is the eighth most common cancer in the United States and clear cell renal carcinoma is the most common type. Many signaling pathways are implicated in clear cell renal carcinoma development, including the inflammation pathway. However, less is known about how gene expression variation in this pathway influences clear cell renal carcinoma development and clinical outcomes. Materials and Methods Gene expression in tumor and adjacent normal tissues from 93 patients was detected using a genome-wide expression array. A panel of 661 inflammation related genes was then analyzed. Differential expression patterns between tumor and normal tissues were identified. Association with recurrence or survival was evaluated with genes showing significant association tested further in a validation set of 258 tumors using an independent platform (quantitative real-time polymerase chain reaction). Results We identified 151 genes with at least a two-fold change in gene expression between adjacent normal tissue and tumor, of which most were up-regulated in tumors. A total of 20 genes significantly associated with recurrence and/or overall survival were selected for further validation. In the replication data set high expression of GADD45G was significantly associated with a 2.09-fold (95% CI 1.08 – 6.14, p = 0.034) increased risk of recurrence while high CARD9, NCF2 and CIITA expression was significantly associated with a 2.52-fold (95% CI 1.24 –5.12, p = 0.010), 2.26-fold (95% CI 1.12– 4.58, p = 0.023) and 2.11-fold (95% CI 1.05– 4.27, p = 0.037) increased risk of death, respectively. Conclusions Results suggest that inflammation gene expression may be significant prognostic biomarkers for the risk of recurrence (GADD45G) and death (CARD9, CIITA and NCF2) in patients with clear cell renal carcinoma.

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Section: Discussionmentioning

confidence: 99%

Role of Inflammatory Related Gene Expression in Clear Cell Renal Cell Carcinoma Development and Clinical Outcomes

Tan

Hildebrandt

et al. 2011

Journal of Urology

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“…Previous studies suggested that immunohistochemically detectable HLA-DRB1 expression is associated with better prognosis in patients with colorectal cancer [10, 11, 12]. The relationship between HLA-DRB1 and AIDs has also been reported.…”

Section: Introductionmentioning

confidence: 97%

Hypomethylation of HLA-DRB1 and its clinical significance in psoriasis

Zong

Han

et al. 2016

Oncotarget

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Increasing evidences indicate that the abnormal DNA methylation is involved in the pathogenesis of psoriasis. A number of SNPs in HLA-DRB1 have been found being associated with the risk of psoriasis, however it is unclear that metylation status within HLA-DRB1 in psoriasis. Here, DNA and RNA were obtained from epidermis of 56 patients with plaque psoriasis and 28 healthy volunteers served as the control group. For the first time, we discovered mean methylation rate for HLA-DRB1 is 52.2%, 64.3% and 68.1% in epidermis from psoriatic lesions, psoriatic non-lesions and healthy controls, respectively. HLA-DRB1 methylation in psoriatic lesions is significantly lower than in psoriatic non-lesions (t = 13.077, p < 0.001). However, there is no significant difference for HLA-DRB1 methylation between in psoriatic non-lesions and in healthy controls (t = 1.046, p = 0.299). HLA-DRB1 methylation in psoriatic lesions is negatively correlated to PASI score (r = -0.431, p = 0.001). HLA-DRB1 methylation in psoriatic lesions of the patients with onset age=18 years is significantly lower than the other patients (t = 3.968, p < 0.001). Meanwhile, HLA-DRB1 mRNA expression is significantly increased in psoriatic lesions comparing to psoriatic non-lesions (t = 12.119, p < 0.001). There are no significant difference for HLA-DRB1 mRNA expression between in psoriatic non-lesions and in healthy controls (t = 1.172, p = 0,245). Moreover, HLA-DRB1 mRNA expression is negatively associated with HLA-DRB1 methylation in psoriatic lesions (r = 0.932, p < 0.001). In conclusions, our results showed hypomethylation of HLA-DRB1 is associated with HLA-DRB1 mRNA expression and severity of the disease, indicating that hypomethylation of HLA-DRB1 may play roles in the pathogenesis of psoriasis.

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“…In rectal cancer specifically, only a few studies reported on the role of the immune system, in which expression of HLA Class I was related to a better prognosis [26,27]. Recently, more studies showed differences in biology between colon- and rectal cancer [28-30].…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of HLA class I, HLA-E, HLA-G and Tregs in rectal cancer: a retrospective cohort study

et al. 2014

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BackgroundEvasion of immune surveillance and suppression of the immune system are important hallmarks of tumorigenesis. The goal of this study was to establish distinct patterns that reflect a rectal tumors’ immune-phenotype and to determine their relation to patient outcome.MethodsThe study population consisted of 495 Stage I-IV non-preoperatively treated rectal cancer patients of which a tissue micro array (TMA) was available. Sections of this TMA were immunohistochemically stained and quantified for presence of Foxp3+ cells (Tregs) and tumor expression of HLA Class I and non-classical HLA-E and HLA-G. All markers were, separate and combined, analyzed for clinical prognostic value.ResultsExpression of HLA class I (DFS HR 0.637 (0.458-0.886), p = 0.013), Foxp3+ infiltration above median (OS HR 0.637 (0.500-0.813), p < 0.001 and DFS HR 0.624 (0.491-0.793), p < 0.001) and expression of HLA-G (DFS HR 0.753 (0.574-0.989), p = 0.042) were related to a better clinical prognosis. When these markers were combined, patients with 2 or 3 markers associated with poor prognosis (loss of HLA Class I, Foxp3+ below median, and weak HLA-G expression), showed a significantly worse survival (OS and DFS p < 0.001). This immune-phenotype was an independent predictor for DFS (HR 1.56 (1.14-2.14), p = 0.019).ConclusionsIn conclusion, rectal tumors showing loss of HLA class I expression, Foxp3+ infiltration below median and weak HLA-G expression were related to a worse OS and DFS. Combining these immune markers lead to the creation of tumor immune-phenotypes , which related to patient outcome and were significant independent clinical prognostic markers in rectal cancer.

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Epithelial Human Leukocyte Antigen-DR Expression Predicts Reduced Recurrence Rates and Prolonged Survival in Rectal Cancer Patients

Cited by 22 publications

References 36 publications

Role of Inflammatory Related Gene Expression in Clear Cell Renal Cell Carcinoma Development and Clinical Outcomes

Role of Inflammatory Related Gene Expression in Clear Cell Renal Cell Carcinoma Development and Clinical Outcomes

Hypomethylation of HLA-DRB1 and its clinical significance in psoriasis

Prognostic value of HLA class I, HLA-E, HLA-G and Tregs in rectal cancer: a retrospective cohort study

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