Synergistic expression of survivin and TK1 in breast cancer tissues and its clinical significance

doi:10.16150/j.1671-2870.2025.05.007

Abstract

Abstract:

Objective This study aims to analyze the expression of survivin/BIRC5 and its related genes in breast cancer, as well as their clinicopathological and prognostic roles. Methods The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze survivin expression differences between breast cancer and normal breast tissues, identify the gene most strongly correlated with survivin, and evaluate their association with breast cancer stages. The Kaplan-Meier plotter database was used to assess the relationship between the expression of survivin and related genes and prognosis of breast cancer patients. Immunohistochemistry (IHC) was performed on 96 postoperative breast cancer tissue specimens, collected from January 2016 to March 2019, to validate the expression of survivin and related genes, analyze their correlation, and assess clinicopathological and prognostic significance (5-year overall survival [OS] rate and 5-year disease-free survival [DFS] rate). Results Bioinformatics analysis of the GEPIA database showed that survivin expression was significantly elevated in breast cancer tissues. The gene with the strongest correlation with its expression was thymidine kinase 1 (TK1), which was also over-expressed in breast cancer tissues. Both of them exhibited synergistic expression, increasing with advanced cancer stages (P<0.05) and correlating negatively with recurrence-free survival in breast cancer patients (P<0.001). IHC results from postoperative tissue samples confirmed a significant positive correlation between survivin and TK1 expression levels. Survivin expression correlated with lymph node metastasis and TNM stage (P<0.01), while TK1 correlated with histological grade, lymph node metastasis, and TNM stage (P<0.05). Survivin and TK1 co-expression was observed in 28 cases (29.17%), showing significant associations with higher histological grade, lymph node metastasis, and advanced-stage disease (P<0.05). In prognostic analysis, the five-year OS rate and five-year DFS rate were 61.5% and 47.9%, respectively. Positive survivin (OS HR=2.225, 95%CI: 1.160-4.271, P=0.016; DFS HR=3.594, 95%CI: 2.018-6.401, P<0.001) and TK1 (OS HR=3.176, 95%CI:1.658-6.083, P<0.001; DFS HR=3.609, 95%CI: 2.057-6.330, P<0.001) predicted poorer prognosis, with co-expression showing higher hazard ratios (5-year OS HR=4.486, 95%CI: 2.335-8.617, P<0.001; 5-year DFS HR=4.469, 95%CI: 2.515-7.942, P<0.001). Conclusions Survivin and TK1 exhibit strong synergistic expression in breast cancer tissues. Their co-expression indicates high grade, lymph node metastasis, advanced stage, and poor prognosis. The combined detection of survivin and TK1 is of great significance for evaluating the clinicopathology and prognosis of breast cancer.

Key words: Breast cancer, Survivin, Thymidine kinase1, Clinicopathology, Prognosis

CLC Number:

R737.9
R446

XU Tu, SHI Chuntao, HAN Wei, YAO Liqian, CHEN Chaobo, FANG Ling, GU Tingting. Synergistic expression of survivin and TK1 in breast cancer tissues and its clinical significance[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(05): 518-528.

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Gene symbol	Genc ID	R
TK1	ENSG00000167900.11	0.82
ALYREF	ENSG00000183684.7	0.70
KIF2C	ENSG00000142945.12	0.64
NCAPH	ENSG00000121152.9	0.64
PLK1	ENSGU000166851.14	0.64
KIF4A	ENSG00000N9088911	0.63
AURKB	ENSG00000178999.12	0.63
TROAP	ENSG00000135451.12	0.63
CCNB2	ENSG00000157456.7	0.63
IPX2	ENSGU0000D88325.15	0.63

Items	Univariate analysis			Multivariate analysis
Items	HR	95%CI	P	HR	95%CI	P
Overall survival
Survivin: Positive vs Negative	2.225	1.160-4.271	0.016	1.130	0.522-2.446	0.756
TK1: Positive vs Negative	3.176	1.658-6.083	<0.001	1.928	0.907-4.100	0.088
Age: ≥56 y vs <56 y	0.992	0.520-1.890	0.980	1.427	0.723-2.817	0.306
Tumor size: >5 cm vs ≤5 cm	1.988	1.037-3.812	0.039	1.327	0.667-2.643	0.421
Histological differentiation: 3 vs 1-2	2.203	1.153-4.208	0.017	1.241	0.623-2.474	0.539
Lymph node metastasis: Yes vs No	4.064	1.439-11.479	0.008	0.929	0.251-3.443	0.913
TNM stage: Ⅲ and Ⅳ vsⅠ and Ⅱ	7.089	3.412-14.728	<0.001	5.705	2.218-14.671	<0.001
Disease-free survival
Survivin: Positive vs Negative	3.594	2.018-6.401	<0.001	2.448	1.201-4.989	0.014
TK1: Positive vs Negative	3.609	2.057-6.330	<0.001	1.997	1.035-3.854	0.039
Age: ≥56 y vs <56 y	0.845	0.484-1.474	0.553	0.829	0.446-1.543	0.555
Tumor size: >5 cm vs ≤5 cm	1.381	0.774-2.461	0.274	1.101	0.578-2.097	0.769
Histological differentiation: 3 vs 1-2	1.344	0.748-2.414	0.322	0.694	0.363-1.325	0.268
Lymph node metastasis: Yes vs No	2.398	1.164-4.940	0.018	0.805	0.316-2.054	0.650
TNM stage: Ⅲ and Ⅳ vs Ⅰ and Ⅱ	5.015	2.802-8.976	<0.001	4.225	1.904-9.376	<0.001

Items	Univariate analysis			Multivariate analysis
Items	HR	95%CI	P	HR	95%CI	P
Overall survival
Survivin+TK1+: Yes vs No	4.486	2.335-8.617	<0.001	2.951	1.455-5.983	0.003
Age: ≥56 y vs <56 y				1.542	0.778-3.055	0.215
Tumor size: >5 cm vs ≤5 cm				1.285	0.646-2.558	0.475
Histological differentiation: 3 vs 1-2				1.064	0.525-2.158	0.863
Lymph node metastasis: Yes vs No				0.887	0.242-3.255	0.857
TNM stage: Ⅲ and Ⅳ vs Ⅰ and Ⅱ				5.806	2.249-14.989	<0.001
Disease-free survival
Survivin+TK1+: Yes vs No	4.469	2.515-7.942	<0.001	3.575	1.875-6.815	<0.001
Age: ≥56 y vs <56 y				0.988	0.547-1.783	0.967
Tumor size: >5 cm vs ≤5 cm				0.945	0.505-1.769	0.860
Histological differentiation: 3 vs 1-2				0.608	0.313-1.181	0.142
Lymph node metastasis: Yes vs No				0.879	0.347-2.225	0.786
TNM stage: Ⅲ and Ⅳ vs Ⅰ and Ⅱ				4.910	2.231-10.805	<0.001