Dataset Information

Prognostic Role of KRAS mRNA Expression in Breast Cancer.

ABSTRACT: Purpose:We investigated the prognostic role of KRAS mRNA expression in breast cancer using The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Methods:Clinical and biological data of 1,093 breast cancers from TCGA database and 1,904 breast cancers from METABRIC database were analyzed. Overall survival (OS) and breast cancer-specific survival (BCSS) were determined. Results:The group with high KRAS mRNA expression showed worse survival than the group with low KRAS mRNA expression regarding both OS (p = 0.012 in TCGA, p < 0.001 in METABRIC) and BCSS (p = 0.001 in METABRIC). According to multivariate analysis, the level of KRAS mRNA expression was an independent prognostic factor in both TCGA (hazard ratio [HR], 1.570; 95% confidence interval [CI], 1.026-2.403; p = 0.038) and METABRIC (HR, 1.254; 95% CI, 1.087-1.446; p = 0.002) databases. The prognostic impact of mRNA expression was effective only for luminal A subtype (p < 0.001 in METABRIC). Positive correlation was observed between mRNA expression and copy number alteration (CNA) (r = 0.577, p < 0.001 in TCGA; ? = 0.343, p < 0.001 in METABRIC). Methylation showed negative correlations with both mRNA expression and CNA (r = -0.272, p < 0.001 in TCGA). The expression of mRNA had little association with the mutation status in breast cancers, having a mutation frequency of approximately 0.6%. Conclusion:KRAS mRNA expression was significantly associated with breast cancer prognosis. It was found to be an independent prognostic factor for breast cancer. Prognostic role of KRAS mRNA expression was effective only in luminal A subtype. Further studies are needed to validate the prognostic role of KRAS mRNA expression in breast cancer, thus paving a way for clinical application of KRAS in practice.

SUBMITTER: Hwang KT

PROVIDER: S-EPMC6933029 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Prognostic Role of <i>KRAS</i> mRNA Expression in Breast Cancer.

Hwang Ki-Tae KT Kim Byoung Hyuck BH Oh Sohee S Park So Yeon SY Jung Jiwoong J Kim Jongjin J Choi In Sil IS Jeon Sook Young SY Kim Woo-Young WY

Journal of breast cancer 20191201 4

<h4>Purpose</h4>We investigated the prognostic role of <i>KRAS</i> mRNA expression in breast cancer using The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases.<h4>Methods</h4>Clinical and biological data of 1,093 breast cancers from TCGA database and 1,904 breast cancers from METABRIC database were analyzed. Overall survival (OS) and breast cancer-specific survival (BCSS) were determined.<h4>Results</h4>The group with high <i>KRAS</ ...[more]

PMID: 31897329

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Project description:Extracellular, cancer-specific methylated DNA has been shown to be a prognostic marker when detected in serum or plasma. In this study we investigated the effect of treating cancer cells with differentially methylated CpG DNA. When breast cancer cell lines were treated with methylated CpG DNA, a consistent upregulation of CHAC1 mRNA expression was observed. CHAC1 was recently described to be a novel component of the unfolded protein response pathway. To elucidate the role of CHAC1 mRNA expression in cancer in more detail, we analyzed expression of this gene in breast (n=107) and ovarian cancer (n=107) and found a strong correlation with tumor differentiation. Poorly differentiated tumors exhibited higher CHAC1 expression levels (p=0.004 for breast and p=0.031 for ovarian cancer). Additionally, hormone receptor (HR)-negative breast cancers (p<0.001) and advanced stage disease ovarian cancers (p=0.026) also demonstrated high CHAC1 mRNA levels. mRNA expression analysis of the two known CHAC1 isoforms showed a strong association of expression above the median with poor outcome in breast cancer patients in a multivariate analysis (isoform a: relative risk (RR) of death 3.2 (95% CI 1.6-6.5; p<0.01); RR of relapse 3.9 (95% CI 1.6-9.8; p<0.01); isoform b: relative risk (RR) of death 3.5 (95% CI 1.6-7.3; p<0.01); RR of relapse 6.6 (95% CI 2.4-18.5; p<0.01)). Univariate analysis in ovarian cancer showed that CHAC1 mRNA expression above the median was associated with a poor relapse free survival (p=0.03). In younger ovarian cancer patients (age < median age), a high CHAC1 mRNA expression was associated with overall survival (p=0.007) and relapse free survival (p=0.015). Finally, we show that downregulation of CHAC1 by small interfering RNA suppressed breast cancer cell migration and proliferation, whereas overexpression resulted in an observed increase in these cellular behaviours. This is the first report demonstrating that a gene (CHAC1) whose expression is triggered by methylated, but not unmethylated DNA, is involved in tumour biology. Human breast cancer cell lines (BT-20, Hs578T) were treated with methylated and unmethylated DNA oligos, and differentially expressed genes were identified between treatments with methylated and un-methylated oligos.

Project description:BackgroundCyclooxygenases (COX) play a key role in prostaglandin metabolism and are important for tumor development and progression. The aim of this study was to analyze the prognostic impact of COX-2 expression in a cohort of lymph node-negative breast cancer patients not treated in the adjuvant setting.MethodsCOX-2 expression was determined by immunohistochemistry (IHC) in tumor tissue of 193 node-negative breast cancer patients. Additionally, mRNA expression was determined in corresponding tumor samples using microarray based gene-expression data. Univariate and multivariate Cox regression analyses adjusted for age at diagnosis, tumor size, histological grade, human epithelial growth factor receptor 2 (HER2), estrogen receptor (ER) and progesterone receptor (PR) were performed to evaluate the association of both COX-2 protein and mRNA expression with survival. Survival rates were determined by the Kaplan-Meier method. Correlations between COX-2 expression and established prognostic factors were analyzed using the Chi-square test. A potential correlation between COX-2 protein expression and COX-2 mRNA expression was assessed utilizing the Kruscal-Wallis-H-test.ResultsCOX-2 protein expression was positive in 24.9% of the breast cancer samples. Univariate analysis showed that COX-2 protein expression was associated with shorter disease-free survival (DFS) (P = 0.0001), metastasis-free survival (MFS) (P = 0.002) as well as breast cancer specific overall survival (OS) (P = 0.043). In multivariate analysis COX-2 expression retained its significance independent of established prognostic factors for shorter DFS (P < 0.001, HR = 2.767, 95% CI = 1.563-4.901) and for inferior MFS (P = 0.002, HR = 2.7, 95% CI = 1.469-5.263) but not for OS (P = 0.096, HR = 1.929, 95% CI = 0.889-4.187). In contrast, COX-2 mRNA expression was not related to survival and failed to show a correlation with protein expression (P = 0.410).ConclusionsThe present findings support the hypothesis that COX-2 protein but not mRNA expression is associated with an unfavorable outcome in node-negative breast cancer.

Dataset Information

Prognostic Role of KRAS mRNA Expression in Breast Cancer.

Publications

Prognostic Role of <i>KRAS</i> mRNA Expression in Breast Cancer.

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