KRT19 is a Promising Prognostic Biomarker and Associates with Immune Infiltrates in Serous Ovarian Cystadenocarcinoma

Figures & data

Table 1 Clinical Characteristics of OV Patients

Characteristics	Low Expression of KRT19	High Expression of KRT19	p value
n	189	190
FIGO stage, n (%)			0.029*
Stage I	1 (0.3%)	0 (0%)
Stage II	10 (2.7%)	13 (3.5%)
Stage III	158 (42%)	137 (36.4%)
Stage IV	20 (5.3%)	37 (9.8%)
Primary therapy outcome, n (%)			0.466
PD	14 (4.5%)	13 (4.2%)
SD	13 (4.2%)	9 (2.9%)
PR	17 (5.5%)	26 (8.4%)
CR	107 (34.7%)	109 (35.4%)
Race, n (%)			0.065
Asian	7 (1.9%)	5 (1.4%)
Black or African American	18 (4.9%)	7 (1.9%)
White	159 (43.6%)	169 (46.3%)
Age, median (IQR)	61 (52, 71)	57 (50, 66)	0.008**

Notes: The number in bold represented significant difference. *p < 0.05; **p < 0.01.

Abbreviations: FIGO stage, International Federation of Gynecology and Obstetrics stage; PD, progressive disease; SD, stable disease; PR, partial remission; CR, complete remission.

Figure 1 Expression patterns of KRT19 in tumors and normal tissues. (A) KRT19 mRNA levels in distinct tumors and normal controls using TCGA and GTEx databases. (B) KRT19 expression in OV and normal ovarian tissues based on TCGA, GTEx and GEO databases. (C) KRT19 protein levels in OV and normal ovarian tissues analyzed by the UALCAN database. (D) Representative results of immunohistochemically stained KRT19 proteins in OV and normal ovarian tissues from Human Protein Atlas. ns, no significant difference; *p < 0.05; **p < 0.01; ***p < 0.001.

Table 2 Correlations Between OS and mRNA Expression of KRT19 Analyzed by Univariate and Multivariate Cox Regression

Characteristics	Total (N)	Univariate Analysis		Multivariate Analysis
		Hazard Ratio (95% CI)	p value	Hazard Ratio (95% CI)	p value
FIGO stage	374
Stage I&Stage II	24	Reference
Stage III	293	2.045 (0.905–4.621)	0.085	2.486 (0.904–6.838)	0.078
Stage IV	57	2.495 (1.057–5.889)	0.037*	2.446 (0.853–7.014)	0.096
Primary therapy outcome	307
PD	27	Reference
SD	22	0.441 (0.217–0.895)	0.023*	0.437 (0.211–0.903)	0.025*
PR	42	0.652 (0.384–1.107)	0.113	0.574 (0.327–1.007)	0.053
CR	216	0.152 (0.093–0.247)	<0.001***	0.148 (0.089–0.247)	<0.001***
Race	364
Asian&Black or African American	37	Reference
White	327	0.637 (0.405–1.004)	0.052	0.662 (0.388–1.129)	0.130
KRT19	377
Low	188	Reference
High	189	1.349 (1.040–1.750)	0.024*	1.519 (1.122–2.057)	0.007**

Notes: The number in bold represented significant difference. *p < 0.05; **p < 0.01; ***p < 0.001.

Abbreviations: OS, overall survival; CI, confidence interval; FIGO stage, International Federation of Gynecology and Obstetrics stage; PD, progressive disease; SD, stable disease; PR, partial remission; CR, complete remission.

Figure 2 Diagnostic and prognostic value of KRT19 in OV. (A–C) Kaplan–Meier curves for OS, PFI and DSS in OV patients. Effects of KRT19 expression on PFI in pathologic stages of OV for FIGO stages I and II (D), FIGO stages III and IV (E), PD and SD (F), PR and CR (G). (H) ROC curve of KRT19 mRNA expression in OV cohort.

Abbreviations: OS, overall survival; PFI, progress free interval; DSS, disease-specific survival; FIGO stage, International Federation of Gynecology and Obstetrics stage; PD, progressive disease; SD, stable disease; PR, partial remission; CR, complete remission; HR, hazard ratio.

Figure 3 Univariate and multivariate regression analysis of KRT19 and clinicopathologic factors with OS in OV patients.

Abbreviations: FIGO stage, International Federation of Gynecology and Obstetrics stage; PD, progressive disease; SD, stable disease; PR, partial remission; CR, complete remission; HR, hazard ratio; CI, confidence interval.

Figure 4 Enrichment hallmarks from the gene set enrichment analysis (GSEA). (A) Apical junction. (B) Inflammatory response. (C) TNFA signaling via NFKB. (D) Epithelial mesenchymal transition.

Abbreviations: NES, normalize enrichment score; FDR, false discovery rate adjustment.

Figure 5 Gene expression and enrichment of KRT19 associated genes in OV. (A) Heatmap of the top 50 genes positively correlated with KRT19 in OV. (B) Heatmap of the top 50 genes negatively correlated with KRT19 in OV. (C) Enrichment of biological processes with KRT19 co-expression genes in OV by GO–KEGG analysis.

Figure 6 Biological processes regulated by the KRT19 gene in OV from CancerSEA. (A) The positive or negative biological function associated with KRT19 in OV by single cell analysis. (B) The association of KRT19 gene with metastasis and invasion of OV cells. (C) Expression distribution with t-SNE plot of KRT19 in OV. ***p < 0.001.

Figure 7 KRT19 gene expression in various ovarian cells. (A) KRT19 expression in different groups of GSE69428; (B) Density plot in different groups of GSE69428; (C) KRT19 expression in different groups of GSE40595; (D) Density plot in different groups of GSE40595.

Figure 8 Association analysis of KRT19 gene expression with immune infiltration. (A) Correlation between KRT19 expression and 24 tumor-infiltrating lymphocytes. (B–G) Correlations of KRT19 level with immune infiltration level of (B) Neutrophils, (C) NK CD56dim cells, (D) Mast cells, (E) DC cells, (F) Th17 cells, (G) iDC cells, (H) Macrophages, (I) Th1 cells, (J) Tem cells.

Figure 9 Correlation analysis between KRT19 expression and immunoinhibitors and immunostimulators in pan-cancers. (A) Correlation heatmap between KRT19 and immunoinhibitors in tumors. (B) Correlation heatmap between KRT19 and immunostimulators in tumors.

Figure 10 Correlation analysis between KRT19 expression and chemokines and receptors in pan-cancers. (A) Correlation heatmap between KRT19 and chemokines in tumors. (B) Correlation heatmap between KRT19 and receptors in tumors.