Dataset Information

Prognostic Significance of CSN2, CD8, and MMR Status-Associated Nomograms in Patients with Colorectal Cancer.

ABSTRACT:

Background

COP9 signalosome subunit 2 (CSN2) is believed to be involved in human cancer, but its prognostic significance in colorectal cancer (CRC) has not been elucidated.

Patients and methods

We retrospectively analyzed the expression of CSN2 andCD8+ tumor-infiltrating lymphocytes (TILs), and mismatch repair (MMR) status in 267 paraffin-embedded specimens using immunohistochemistry in a training cohort. A number of risk factors were used to form nomograms to evaluate survival, and Harrell's concordance index (C-index) was used to evaluate the predictive accuracy. Further validation was performed in an independent cohort of 238cases.

Results

Low CSN2 expression and a low number of CD8 + TILs were significantly associated with diminished disease-free survival (DFS) and overall survival (OS) in CRC patients, and patients with MMR-deficient CRC had enhanced DFS and OS. Moreover, the multivariate Cox analysis identified CSN2, CD8 + TILs, and MMR status as independent prognostic factors for DFS and OS. Using these three markers and four clinicopathological risk variables, two nomograms were constructed and validated for predicting DFS and OS (C-index: training cohort, 0.836 (95% CI:0.804-0.868) and 0.841 (0.808-0.874), respectively; validation cohort, 0.801 (0.760-843) and 0.843 (0.806-0.881), respectively).

Conclusions

CSN2, CD8+ TILs, and MMR status were independent prognostic factors. The nomograms could be used to generate individualized predictions for DFS and OS.

SUBMITTER: Zhu B

PROVIDER: S-EPMC6080638 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Prognostic Significance of CSN2, CD8, and MMR Status-Associated Nomograms in Patients with Colorectal Cancer.

Zhu Bing B Zhang Pei P Liu Mulin M Jiang Congqiao C Liu Hao H Fu Jun J

Translational oncology 20180731 5

<h4>Background</h4>COP9 signalosome subunit 2 (CSN2) is believed to be involved in human cancer, but its prognostic significance in colorectal cancer (CRC) has not been elucidated.<h4>Patients and methods</h4>We retrospectively analyzed the expression of CSN2 andCD8+ tumor-infiltrating lymphocytes (TILs), and mismatch repair (MMR) status in 267 paraffin-embedded specimens using immunohistochemistry in a training cohort. A number of risk factors were used to form nomograms to evaluate survival, a ...[more]

PMID: 30075461

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Project description:PurposeTo evaluate the relationship between the DNA mismatch repair (MMR) status and histone lysine-specific demethylase 6A (KDM6A) on the prognosis of colorectal cancer (CRC).MethodsAbout 594 patients with CRC from The Cancer Genome Atlas (TCGA) were enrolled in this retrospective study. Subsequently, a series of different classification tests for MMR status, cancer types, and target gene expression was conducted.ResultsAfter filtering out the KDMs group of genes, we selected KDM6A as the target gene. A significant difference in the performance of KDM6A in tumor and normal tissues were confirmed. Our results showed a lower KDM6A expression, lower KDM6A exon expression, and higher KDM6A DNA methylation than their corresponding normal tissues in colon adenocarcinoma (COAD). Notably, the main MMR genes were highly expressed in tumor tissues than normal tissues both in COAD and rectum adenocarcinoma (READ). Moreover, proficient DNA mismatch repair (pMMR) was found to be an important poor prognostic factor in COAD (p = 0.0064) and the low KDM6A expression was an important factor for poor prognosis in READ (p = 0.0217). Based on these results, we consequently relate MMR status with KDM6A expression in predicting the prognosis of patients with CRC. Moreover, patients with pMMR exhibited a low KDM6A expression in COAD (p = 0.0250). Samples were divided into two groups based on the KDM6A expression. Interestingly, the group with low KDM6A expression showed no difference between pMMR and deficient DNA mismatch repair (dMMR) in prognosis, whereas the group with high KDM6A expression was closely related to MMR status in OS (p = 0.0082). Besides, COAD patients with high KDM6A expression and pMMR status had poor OS (p = 0.0082).ConclusionsThe KDM6A/MMR classification-based subtypes of low KDM6A expression/READ, high KDM6A expression/pMMR, and COAD/pMMR were associated with poor prognosis. This classification can be a novel prognostic approach in CRC.

Dataset Information

Prognostic Significance of CSN2, CD8, and MMR Status-Associated Nomograms in Patients with Colorectal Cancer.

Background

Patients and methods

Results

Conclusions

Publications

Prognostic Significance of CSN2, CD8, and MMR Status-Associated Nomograms in Patients with Colorectal Cancer.

Similar Datasets

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