Dataset Information

Combined mRNAs and clinical factors model on predicting prognosis in patients with triple-negative breast cancer.

ABSTRACT:

Objective

Triple-negative breast cancer (TNBC) is aggressive cancer usually diagnosed in young women with no effective prognosis prediction model to use. The present study was performed to develop a useful prognostic model for predicting overall survival (OS) for TNBC patients.

Methods

The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases were used as training and validation data sets, respectively, in which the gene expression levels and clinical prognostic information of TNBC were collected. Differentially expressed genes (DEGs) between TNBC and non-TNBC (NTNBC) were identified with the thresholds of false discovery rate < 0.05 and |log2 Fold Change| > 1. DEGs in AmiGO2 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were retained for further study. Univariate, multivariate Cox, and logistic regression analysis were conducted for detecting DEG signature with the threshold of log-rank P < 0.05. The prognosis models of mRNA signature, clinical factors were constructed and compared.

Results

One five-DEG signature, including CHST4, COCH, CST9, SOX11, and TDGF1 was identified in DEG prognosis model. Stratified analysis showed that the patients aged over 60, with higher pathologic stage (III-IV) and recurrence induced a significantly lower survival rate than those aged below 60, lower pathologic stage and without recurrence. Compared with patients with low-risk scores, those presented high-risk scores demonstrated significantly lower survival rate in the subgroup aged over 60 [HR = 3.780 (1.801-7.933), P < 0.0001]. For patients who obtained a higher pathologic stage and recurrence, high-risk scores were correlated with a significantly lower survival rate than patients with low-risk scores. The five-mRNA signature combined with clinical model (AUC = 0.950) predicted better than single clinical model (AUC = 0.795) or five-mRNA signature model (AUC = 0.823).

Conclusion

Our present study identified a prognostic prediction model (combined with five-mRNA signature and clinical factors) for TNBC patients receiving immunotherapy, which will benefit future research and clinical therapies.

SUBMITTER: Hu Y

PROVIDER: S-EPMC8716048 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionTriple-negative breast cancer (TNBC) is a heterogeneous disease with no definitive prognostic markers. As a major component of tight junctions, claudins (CLDNs) presumably play an important role in carcinogenesis and progression of breast cancer. This study was aimed at determining the relationship between the expression of CLDNs and the clinical outcomes of TNBCs.Materials and methodsThe surgical specimens of primary breast tumors from a consecutive cohort of 173 TNBC patients were retrospectively collected. The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry. Then, the associations between CLDN expression, clinicopathological features, and clinical outcomes were assessed.ResultsPositive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in 44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of CLDN1 expression was related to only lymph node metastasis (P?=?0.014). The rate of CLDN4-positive tumors was significantly increased in tumors of a higher grade (P?=?0.003). Importantly, negative CLDN1 expression was associated with worse relapse-free survival (RFS) in both lymph node positive (LN+) and negative (LN-) cases (both P<0.001). Similarly it was also associated with shorter overall survival (OS)(P?=?0.003 in LN+ cases; P?=?0.018 in LN- cases). In the LN+ subgroup, CLDN2-negative cases had a significantly higher risk of recurrence (P?=?0.008). Multivariate analysis revealed that negative CLDN1 expression was an independent prognostic factor for high risk of both recurrence and death (HR 5.529, 95% CI 2.664-11.475, P<0.001; HR 3.459, 95% CI 1.555-7.696, P?=?0.002). However, neither CLDN4 nor CLDN7 expression was associated with survival.ConclusionIn TNBC, the CLDN1-negative phenotype predicts a high risk of recurrence and death. The absence of CLDN1 expression is strongly suggested to be an independent adverse prognostic factor in this heterogeneous subtype of breast cancer.

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