Low KRT15 expression is associated with poor prognosis in patients with breast invasive carcinoma

Abstract

Although keratin 15 (KRT15) has been indicated to be overexpressed in several types of tumor, its role in breast invasive carcinoma (BRCA) has so far remained elusive. The aim of the present study was to explore KRT15 expression in BRCA based on data obtained from The Cancer Genome Atlas and The Genotype-Tissue Expression. KRT15 expression was compared using a Wilcoxon rank-sum test. Functional enrichment analysis was performed to reveal the biological roles and pathways of KRT15. The association between KRT15 expression and immune-cell infiltration was evaluated via single-sample gene set enrichment analysis (ssGSEA). To investigate the relationship between clinicopathological features and KRT15 expression, the prognostic value of KRT15 and other clinical factors was evaluated using Cox regression analysis and Kaplan-Meier (KM) plots. Subgroup prognostic analysis was also performed using forest plots and KM curves. Finally, a tissue microarray was used to assess KRT15 expression in BRCA tissues. KRT15 expression was significantly lower in BRCA tissues compared with that in normal tissues. Functional enrichment analysis suggested that KRT15-related genes were primarily enriched in the transmembrane transporter complex, cornification and ligand-receptor interactions. Increased KRT15 was associated with several tumor-suppressive pathways. ssGSEA revealed that high KRT15 expression was significantly associated with natural killer-cell, B-cell and mast-cell infiltration. Significant associations were observed between low KRT15 expression and advanced stage clinicopathological factors, as well as unfavorable overall survival (OS) and disease-specific survival. Multivariate Cox regression analysis suggested that KRT15 was an independent prognostic factor for OS (P=0.039; hazard ratio, 0.590; 95% CI, 0.358-0.974). Subgroup prognostic analysis demonstrated that low KRT15 was a reliable predictor of poor OS. Immunohistochemistry of a tissue microarray indicated that positive KRT15 expression rates were significantly higher in normal tissues compared with those in the BRCA tissues. In conclusion, low KRT15 expression was significantly associated with poor prognosis in patients with BRCA. Thus, KRT15 may serve an important role in BRCA progression and may be used as a promising prognostic marker for diagnostic and prognostic analyses in patients with BRCA.

Aspects of the Epigenetic Regulation of EMT Related to Cancer Metastasis

“…Epigenetic silencing of KRT13 genes might be useful for the development of diagnostic markers and novel therapeutic approaches [ 24 ]. KRT15 is associated with tumorigenesis and has different expression characteristics across different types of cancer [ 46 ]. Decreased expression of KRT18 may be dependent on DNA hypermethylation and may serve as a biomarker for the diagnosis of metastasis [ 26 ].…”

Upregulated keratin 15 links to the occurrence of lymphovascular invasion, stromal cervical invasion as well as unfavorable survival profile in endometrial cancer patients

“…[ 12 ] Differently, it is illustrated that KRT15 is downregulated in carcinoma tissue compared with normal tissue from breast cancer patients. [ 14 , 15 , 17 ] KRT15 expression discloses an opposite trend in breast cancer, which might be explained by that: The apoptosis and differentiation of KRT15 would be influenced by endocrine status, hence, we hypothesize that KRT15 expression in breast cancer might be affected by the hormonal environment (such as estrogen, progesterone, etc) [ 18 , 19 ] ; whereas, this speculation needs further investigation in the in vivo and in vitro studies. In the current study, it was discovered that KRT15 was higher in tumor tissue compared with adjacent tissue; meanwhile, it exhibited an acceptable capability in distinguishing tumor tissue from adjacent tissue.…”

“…KRT15 overexpression is linked with immune-cell infiltration of NK cells, mast cells, and B cells whose infiltration might enhance tumor progression in EC. [ 14 ] Thus, KRT15 overexpression is linked with the occurrence of lymphovascular invasion in EC patients. KRT15 upregulation is linked with progressed disease reflected by the occurrence of lymphovascular invasion and stromal cervical invasion; thus, KRT15 upregulation is correlated with higher FIGO stage.…”

“…[20][21][22] Tumor KRT15 is also reported to reflect tumor features such as poor differentiation, metastasis, and advanced clinical stages in several solid carcinomas. [13][14][15] For example, a previous research discloses that upregulated KRT15 is linked with poor differentiation, the occurrence of lymph node metastasis, and a more advanced T stage in colorectal cancer. [12] Besides, another study reveals that KRT15 overexpression is associated with tumor metastasis in breast cancer patients.…”

“…[ 12 ] Another 2 studies also exhibit that KRT15 overexpression is associated with tumor metastasis and poor prognosis in breast cancer patients. [ 14 , 15 ] However, its clinical relevance in EC cancer patients remains elusive; hence, the current study aimed to investigate the KRT15 dysregulation and its correlation with clinical features and survival profile in EC patients.…”