Circulating microRNAs and serum proteins in breast cancer patients: Diagnostic relevance and grade-specific expression patterns

doi:10.5493/wjem.v15.i3.108034

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World Journal of Experimental Medicine

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Exp Med. Sep 20, 2025; 15(3): 108034
Published online Sep 20, 2025. doi: 10.5493/wjem.v15.i3.108034

Table 1 The clinicopathological features of breast cancer patients, n (%)

Parameters		Groups		χ²	P value
Parameters		Grade II	Grade III	χ²	P value
Estrogen receptor	Positive	20 (80.00)	14 (58.30)	2.706	0.100
Estrogen receptor	Negative	5 (20.00)	10 (41.70)
Progesterone receptor	Positive	22 (88.00)	13 (54.20)	6.868	0.009
Progesterone receptor	Negative	3 (12.00)	11 (45.80)
Human epidermal growth factor receptor 2	Positive	19 (76.00)	10 (41.70)	5.975	0.015
Human epidermal growth factor receptor 2	Negative	6 (24.00)	14 (58.30)
Family history	Positive	12 (48.00)	7 (29.20)	1.829	0.176
Family history	Negative	13 (52.00)	17 (70.80)
Tumor size	1	9 (36.00)	2 (8.30)	10.599	0.014
	2	13 (52.00)	10 (41.70)
	3	0 (0.00)	2 (8.30)
	4	3 (12.00)	10 (41.70)
Lymph nodal involvement	0	18 (72.00)	8 (33.30)	7.772	0.050
	1	5 (20.00)	9 (37.50)
	2	1 (4.00)	4 (16.70)
	3	1 (4.00)	3 (12.50)
Metastasis	0	22 (88.00)	18 (75.00)	1.380	0.240
Metastasis	1	3 (12.00)	6 (25.00)
Metastatic	Yes	3 (12.00)	6 (25.00)	1.380	0.240
	No	22 (88.00)	18 (75.00)
Pathological subtype	Invasive ductal carcinoma	21 (84.00)	24 (100.00)	4.181	0.124
	Invasive lobular carcinoma	2 (8.00)	0 (0.00)
	Other	2 (8.00)	0 (0.00)

Table 2 Relative expression values of the selected panel of microRNAs and levels of serum proteins (8-hydroxy-2′-deoxyguanosine and cancer antigen 15-3) in breast cancer patients and healthy control

Parameters	Groups	Minimum	Maximum	mean ± SD	Median	P value
MiR-21	Control	0.64	1.69	0.94 ± 0.24	0.89	0.000
	Grade II patients	1.28	3.79	2.31 ± 0.73^a	2.11
	Grade III patients	3.78	8.54	6.59 ± 1.47^a^,^b	6.84
MiR-221	Control	0.64	1.87	1.07 ± 0.34	0.95	0.000
	Grade II patients	0.89	2.48	1.47 ± 0.37^a	1.41
	Grade III patients	1.36	4.56	2.53 ± 0.95^a^,^b	2.40
MiR-1246	Control	0.12	2.89	1.08 ± 0.57	1.04	0.000
	Grade II patients	1.21	8.32	3.40 ± 1.57^a	3.31
	Grade III patients	1.67	30.45	12.02 ± 7.85^a^,^b	9.17
MiR-145	Control	0.41	1.09	0.80 ± 0.21	0.88	0.000
	Grade II patients	0.21	0.71	0.38 ± 0.14^a	0.34
	Grade III patients	0.08	0.56	0.22 ± 0.13^a^,^b	0.19
MiR-382	Control	0.26	1.18	0.80 ± 0.26	0.86	0.000
	Grade II patients	0.13	0.79	0.39 ± 0.16^a	0.35
	Grade III patients	0.04	0.79	0.26 ± 0.24^a	0.19
8-hydroxy-2′-deoxyguanosine (Pg/mL)	Control	643.00	2648.00	917.60 ± 515.30	740.00	0.000
	Grade II patients	1849.00	3997.00	3292.92 ± 611.56^a	3096.00
	Grade III patients	1849.00	3997.00	3480.00 ± 662.59^a	3757.00
Cancer antigen 15-3 (U/mL)	Control	15.87	135.60	38.12 ± 41.91	20.67	0.000
	Grade II patients	119.70	420.00	241.94 ± 86.34^a	222.40
	Grade III patients	122.40	435.30	311.00 ± 90.83^a^,^b	319.85

^aP < 0.05, significant difference compared to control at a significant level.

^bP < 0.05, significant difference between grade II and grade III breast cancer patients at a significant level.

MiRNAs: MicroRNAs.

Table 3 Spearman’s correlation coefficient between microRNAs and tumor biomarkers

	MiR-21	MiR-221	MiR-1246	MiR-145	MiR-382	8-OHdG	CA15-3
MiR-21	1.00	0.678^a	0.764^a	-0.738^a	-0.755^a	0.644^a	0.694^a
MiR-221		1.00	0.625^a	-0.600^a	-0.542^a	0.537^a	0.472^a
MiR-1246			1.00	-0.681^a	-0.632^a	0.650^a	0.684^a
MiR-145				1.00	-0.681^a	-0.515^a	-0.663^a
MiR-382					1.00	-0.576^a	-0.500^a
8-OHdG						1.00	0.546^a
CA15-3							1.00

^aP < 0.01, correlation is significant.

CA15-3: Cancer antigen 15-3; MiRNAs: MicroRNAs; 8-OhdG: 8-hydroxy-2′-deoxyguanosine.

Table 4 Diagnostic performance of microRNAs and other tumor biomarkers in breast cancer patients (grade II) relative to the control group

Parameters	Area under the curve	Cut-off value	Sensitivity (%)	Specificity (%)	P value	95%CI
MiR-21	0.988	1.25	100.0	95.0	0.000	0.962-1.000
MiR-221	0.804	1.06	88.0	75.0	0.001	0.664-0.944
MiR-1246	0.974	1.99	92.0	95.0	0.000	0.935-1.000
MiR-145	0.950	0.46	84.0	95.0	0.000	0.893-1.000
MiR-382	0.888	0.77	96.0	75.0	0.000	0.780-0.996
8-OHdG	0.996	1822.00	100.0	95.0	0.000	0.985-1.000
Cancer antigen 15-3	0.982	158.15	88.0	100.0	0.000	0.953-1.000
MiR-145 + MiR-382 + MiR-1246	1.000	-	100.0	100.0	0.000	1.000-1.000
MiR-145 + 8-OHdG	1.000	-	100.0	100.0	0.000	1.000-1.000

MiRNAs: MicroRNAs; 8-OhdG: 8-hydroxy-2′-deoxyguanosine.

Table 5 Diagnostic performance of microRNAs and other tumor biomarkers in breast cancer patients (grade III) relative to the control group

Parameters	Area under the curve	Cut-off value	Sensitivity (%)	Specificity (%)	P value	95%CI
MiR-21	1.000	2.73	100.0	100.0	0.000	1.000-1.000
MiR-221	0.946	1.20	100.0	75.0	0.000	0.886-1.000
MiR-1246	0.990	2.035	95.8	95.0	0.000	0.969-1.000
MiR-145	0.978	0.35	87.5	100.0	0.000	0.945-1.000
MiR-382	0.950	0.305	79.2	95.0	0.000	0.894-1.000
8-hydroxy-2′-deoxyguanosine	0.994	1822.00	100.0	95.0	0.000	0.979-1.000
Cancer antigen 15-3	0.985	178.00	87.5	100.0	0.000	0.961-1.000
MiR-382 + MiR-221	0.992	-	95.8	100.0	0.000	0.973-1.000

MiRNAs: MicroRNAs.

Table 6 Diagnostic performance of microRNAs and other tumor biomarkers for differentiating between breast cancer patients (grade II vs grade III)

Parameters	Area under the curve	Cut-off value	Sensitivity (%)	Specificity (%)	P value	95%CI
MiR-21	0.997	3.79	95.83	100.00	0.001	0.921-1.000
MiR-221	0.843	2.11	75.00	96.00	0.001	0.711-0.931
MiR-1246	1.000	4.26	100.00	100.00	0.001	0.927-1.000
MiR-145	0.941	0.26	91.67	88.00	0.001	0.834-0.988
MiR-382	0.952	0.24	87.50	92.00	0.001	0.849-0.992
8-hydroxy-2′-deoxyguanosine	0.627	3232	79.17	56.00	0.125	0.477-0.761
Cancer antigen 15-3	0.768	235.3	87.50	68.00	0.001	0.626-0.877

MiRNAs: MicroRNAs.

Citation: El-Toukhy SE, Nabih HK, Kamel MM, Elmasry H, El-Daly SM. Circulating microRNAs and serum proteins in breast cancer patients: Diagnostic relevance and grade-specific expression patterns. World J Exp Med 2025; 15(3): 108034
URL: https://www.wjgnet.com/2220-315X/full/v15/i3/108034.htm
DOI: https://dx.doi.org/10.5493/wjem.v15.i3.108034