The Combination of circEPSTI1 and MIF Offers Diagnostic Value for Endometrial Cancer

Figures & data

Table 1 Clinicopathological Characteristics of EC Patients and Controls

Characteristics	EC (%)	Healthy Controls (%)
Age
<55	39 (20.97)	60 (32.26)
≥55	147 (79.03)	126 (67.74)
Histological type
Endometrioid	154 (82.80)
Mixed	10 (5.38)
Serous	22 (11.82)
Stage
I	120 (64.52)
II	19 (10.22)
III	32 (17.20)
IV	15 (8.06)
Diabetes
No	102 (54.84)
Yes	46 (24.73)
NA	38 (20.43)
Hypertension
No	65 (34.95)
Yes	98 (52.69)
NA	23 (12.37)
Histologic grade
G1	35 (18.82)
G2	56 (30.11)
G3	88 (47.31)
High grade	7 (3.76)
Menopause status
Indeterminate	11 (5.91)
Peri-Menopause	13 (6.99)
Post-menopause	129 (69.35)
Pre-menopause	18 (9.68)
NA	15 (8.07)
Residual tumor
R0	114 (61.29)
R1	13 (6.99)
R2	9 (4.83)
Rx	23 (12.37)
NA	27 (14.52)

Table 2 Relationships Between circEPSTI1 Expression Levels and Patient Clinicopathological Characteristics

Clinical Characteristics	Number	circEPSTI1 Expression		P value
		Low	High
Age				0.652
<55	39	18	21
≥55	147	75	72
Histological type				0.352
Endometrioid	154	77	77
Mixed	10	6	4
Serous	22	10	12
Stage				0.031
I	120	72	48
II	19	8	11
III	32	9	23
IV	15	4	11
Diabetes				0.186
No	102	59	43
Yes	46	19	27
Hypertension				0.854
No	65	32	33
Yes	98	42	56
Histologic grade				0.029
G1	35	25	10
G2	56	36	20
G3	88	31	57
High grade	7	1	6
Menopause status				0.309
Indeterminate	11	6	5
Peri-Menopause	13	6	7
Post-menopause	129	63	66
Pre-menopause	18	10	8
Residual tumor				0.022
R0	114	70	44
R1	13	8	5
R2	9	3	6
Rx	23	7	16

Table 3 Univariate and Multivariate Cox Analyses of PFS-Related Factors in EC Patients

Variables	Univariate Analysis		p value	Multivariate Analysis		p value
	HR	95% CI		HR	95% CI
Age (Years)	0.521	0.251–0.985	0.351	–	–	–
Histological type	0.481	0.218–0.854	0.311	–	–	–
Stage	1.625	0.529–2.519	0.034	1.458	0.352–2.221	0.035
Diabetes	0.428	0.365–1.258	0.481	–	–	–
Hypertension	0.558	0.118–0.849	0.352	–	–	–
Histologic grade	2.015	0.511–2.719	0.025	1.982	0.658–2.419	0.028
Menopause status	0.522	0.185–0.971	0.246	–	–	–
Residual tumor	1.952	1.152–2.254	0.019	1.845	0.954–2.197	0.021
circEPSTI1 expression	2.512	1.025–3.251	0.011	2.197	0.981–2.971	0.015

Table 4 Univariate and Multivariate Cox Analyses of OS-Related Factors in EC Patients

Variables	Univariate Analysis		p value	Multivariate Analysis		p value
	HR	95% CI		HR	95% CI
Age (Years)	0.452	0.341–0.881	0.391	–	–	–
Histological type	0.512	0.271–0.919	0.291	–	–	–
Stage	1.522	0.418–2.025	0.037	1.441	0.519–1.957	0.041
Diabetes	0.537	0.415–1.192	0.405	–	–	–
Hypertension	0.395	0.251–0.719	0.334	–	–	–
Histologic grade	1.952	0.397–2.518	0.026	1.852	0.418–2.228	0.03
Menopause status	0.494	0.251–0.819	0.319	–	–	–
Residual tumor	1.825	1.002–2.295	0.025	1.719	1.128–2.341	0.027
circEPSTI1 expression	2.417	1.102–3.025	0.014	2.027	1.249–2.843	0.018

Figure 1 Patients with EC exhibit elevated serum levels of circEPSTI1. (A) The genomic loci of circEPSTI1 and the Sanger sequence of junction site of circEPSTI1. (B) Serum samples from EC patients and healthy subjects were assessed to compare serum circEPSTI1 expression, which was found to be elevated in individuals diagnosed with EC. ***P<0.001.

Figure 2 Serum levels of circEPSTI1 are related to the clinicopathological characteristics of patients with EC. Log rank tests were utilized to assess the PFS (A) and OS (B) of patients exhibiting low or high circEPSTI1 expression.

Figure 3 Evaluation of the expression and diagnostic value of MIF in patients with EC. (A) Serum MIF concentrations were elevated in EC patients as compared to healthy subjects. (B) Serum MIF concentrations were able to distinguish between EC patients and control subjects in ROC curve analyses. ***P<0.001.

Figure 4 Serum circEPSTI1 offers diagnostic value for the detection of EC. (A) Serum levels of circEPSTI1 were able to effectively distinguish between EC patients and controls when constructing an ROC curve. (B) An ROC curve analysis was conducted for the combination of circEPSTI1 and MIF to more effectively distinguish between healthy subjects and individuals with EC.