World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://wjon.elmerpub.com

Original Article

Volume 16, Number 1, February 2025, pages 104-112

Methylation of SOX1 and PAX1 Are Risk Factors and Potential Biomarkers for Cervical Lesions

Figure 1. H&E staining images of patients in each group (× 100). (a) Inflammation group. (b) LSIL group. (c) HSIL group. (d) CSCC group. H&E: hematoxylin and eosin stain; LSIL: low-grade squamous intraepithelial lesion; HSIL: high-grade squamous intraepithelial lesion; CSCC: cervical squamous cell carcinoma.

Figure 2. Methylation index of PAX1 (a) and SOX1 (b) in paraffin-embedded tissue samples of 139 patients undergoing cervical biopsy. LSIL: low-grade squamous intraepithelial lesion; HSIL: high-grade squamous intraepithelial lesion; CSCC: cervical squamous cell carcinoma; M-index: methylation index; PAX1^m: PAX1 methylation; SOX1^m: SOX1 methylation.

Figure 3. Methylation positivity rates of PAX1 and SOX1 in paraffin-embedded tissue samples of 139 patients undergoing cervical biopsy. (a) Methylation positivity rates of PAX1 and SOX1 in cervical biopsy tissue samples of patients in different stages. (b) Methylation positivity rates of PAX1 and SOX1 in cervical biopsy tissue samples of patients in different age groups. (c) Methylation positivity rates of PAX1 and SOX1 in cervical biopsy tissue samples of patients with HPV infection. LSIL: low-grade squamous intraepithelial lesion; HSIL: high-grade squamous intraepithelial lesion; CSCC: cervical squamous cell carcinoma; HPV: human papillomavirus; M-index: methylation index; PAX1^m: PAX1 methylation; SOX1^m: SOX1 methylation.

**Table 1.** The Clinical Characteristics of the 139 Patients
Parameter	Chronic cervicitis	LSIL	HSIL	CSCC
LSIL: low-grade squamous intraepithelial lesion; HSIL: high-grade squamous intraepithelial lesion; CSCC: cervical squamous cell carcinoma; HPV: human papillomavirus.
Number of patients	32	30	50	27
Age
≤ 39	12	15	29	6
40 - 59	14	10	19	18
≥ 60	6	5	2	3
HPV
Positive	2	19	46	24
Negative	30	11	4	3

Table 1. The Clinical Characteristics of the 139 Patients

Parameter

Chronic cervicitis

LSIL

HSIL

CSCC

LSIL: low-grade squamous intraepithelial lesion; HSIL: high-grade squamous intraepithelial lesion; CSCC: cervical squamous cell carcinoma; HPV: human papillomavirus.

Number of patients

Age

≤ 39

40 - 59

≥ 60

HPV

Positive

Negative

**Table 2.** Methylation Index of *PAX1* and *SOX1*
Group	PAX1	SOX1
****P < 0.0001. M-index: methylation index; LSIL: low-grade squamous intraepithelial lesion; HSIL: high-grade squamous intraepithelial lesion; CSCC: cervical squamous cell carcinoma.
Inflammation	0 (0, 0)		0 (0, 0)
LSIL	0 (0, 0.45)	0.1095	0 (0, 0)	0.1718
HSIL	0.9150 (0, 50.01)	< 0.0001****	0 (0, 36.21)	< 0.0001****
CSCC	1,259 (514.7, 5,176)	< 0.0001****	1,743 (625, 3,711)	< 0.0001****

Table 2. Methylation Index of PAX1 and SOX1

Group

PAX1

SOX1

M-index

****P < 0.0001. M-index: methylation index; LSIL: low-grade squamous intraepithelial lesion; HSIL: high-grade squamous intraepithelial lesion; CSCC: cervical squamous cell carcinoma.

Inflammation

0 (0, 0)

LSIL

0 (0, 0.45)

0.1095

0 (0, 0)

0.1718

HSIL

0.9150 (0, 50.01)

< 0.0001****

0 (0, 36.21)

< 0.0001****

CSCC

1,259 (514.7, 5,176)

< 0.0001****

1,743 (625, 3,711)

< 0.0001****

**Table 3.** Methylation Positivity Rates of *PAX1* and *SOX1* in Cervical Biopsy Tissue Samples of 139 Patients
	PAX1^m	SOX1^m	PAX1^m + SOX1^m
PAX1^m: PAX1 methylation; SOX1^m: SOX1 methylation; LSIL: low-grade squamous intraepithelial lesion; HSIL: high-grade squamous intraepithelial lesion; CSCC: cervical squamous cell carcinoma; HPV: human papillomavirus; CI: confidence interval.
Age
≤ 39	30	17	0.27	2.59	30	17	0.65	0.86	25	22	0.9	0.21
	-63.83%	-36.17%			-63.83%	-36.17%			-53.19%	-46.81%
40 - 59	23	24			26	21			24	23
	-48.94%	-51.06%			-55.32%	-44.68%			-51.06%	-48.94%
≥ 60	6	7			7	6			6	7
	-46.15%	-53.85%			-53.85%	-46.15%			-46.15%	-53.85%
HPV
Negative	12	6	0.28	1.16	13	5	0.21	1.59	11	7	0.32	0.98
	-66.67%	-33.33%			-72.22%	-27.78%			-61.11%	-38.89%
Positive	47	42			50	39			43	46
	-52.81%	-47.19%			-56.18%	-43.82%			-48.31%	-51.69%
Cervix
Inflammation	31	1	< 0.0001	65.8	31	1	< 0.0001	50.7	30	2	< 0.0001	60.8
	-96.88%	-3.13%			-96.88%	-3.13%			-93.75%	-6.25%
LSIL	27	3			27	3			26	4
	-90.00%	-10.00%			-90.00%	-10.00%			-86.67%	-13.33%
HSIL	28	22			30	20			24	26
	-56.00%	-44.00%			-60.00%	-40.00%			-48.00%	-52.00%
CSCC	3	24			6	21			3	24
	-11.11%	-88.89%			-22.22%	-77.78%			-11.11%	-88.89%

Table 3. Methylation Positivity Rates of PAX1 and SOX1 in Cervical Biopsy Tissue Samples of 139 Patients

PAX1^m

SOX1^m

PAX1^m + SOX1^m

Negative

Positive

χ²

Negative

Positive

χ²

Negative

Positive

χ²

PAX1^m: PAX1 methylation; SOX1^m: SOX1 methylation; LSIL: low-grade squamous intraepithelial lesion; HSIL: high-grade squamous intraepithelial lesion; CSCC: cervical squamous cell carcinoma; HPV: human papillomavirus; CI: confidence interval.

Age

≤ 39

0.27

2.59

0.65

0.86

0.9

0.21

-63.83%

-36.17%

-63.83%

-36.17%

-53.19%

-46.81%

40 - 59

-48.94%

-51.06%

-55.32%

-44.68%

-51.06%

-48.94%

≥ 60

-46.15%

-53.85%

-46.15%

-53.85%

HPV

Negative

0.28

1.16

0.21

1.59

0.32

0.98

-66.67%

-33.33%

-72.22%

-27.78%

-61.11%

-38.89%

Positive

-52.81%

-47.19%

-56.18%

-43.82%

-48.31%

-51.69%

Cervix

Inflammation

< 0.0001

65.8

< 0.0001

50.7

< 0.0001

60.8

-96.88%

-3.13%

-96.88%

-3.13%

-93.75%

-6.25%

LSIL

-90.00%

-10.00%

-90.00%

-10.00%

-86.67%

-13.33%

HSIL

-56.00%

-44.00%

-60.00%

-40.00%

-48.00%

-52.00%

CSCC

-11.11%

-88.89%

-22.22%

-77.78%

-11.11%

-88.89%

**Table 4.** Sensitivity, Specificity, and Odds Ratios (ORs) of HPV Detection, *PAX1* Methylation Detection, and *SOX1* Methylation Detection in 139 Patients
	Sensitivity	Specificity	OR	P	95% CI
PAX1^m: PAX1 methylation; SOX1^m: SOX1 methylation; LSIL: low-grade squamous intraepithelial lesion; HSIL: high-grade squamous intraepithelial lesion; CSCC: cervical squamous cell carcinoma; HPV: human papillomavirus; CI: confidence interval.
Inflammation/LSIL
HPV	63.33%	93.75%	25.91	< 0.0001	5.17 - 129.94
PAX1^m	10.00%	96.88%	3.44	0.27	0.34 - 35.09
SOX1^m	10.00%	96.88%	3.44	0.27	0.34 - 35.09
PAX1^m + SOX1^m	13.33%	93.75%	2.31	0.35	0.39 - 13.64
Inflammation/HSIL
HPV	92.00%	93.75%	172.5	< 0.0001	29.72 - 1,001.24
PAX1^m	44.00%	96.88%	24.36	< 0.0001	3.08 - 192.67
SOX1^m	40.00%	96.88%	20.67	< 0.0001	2.61 - 163.80
PAX1^m + SOX1^m	52.00%	93.75%	16.25	< 0.0001	3.50 - 75.43
Inflammation/CSCC
HPV	88.89%	93.75%	120	< 0.0001	18.53 - 777.02
PAX1^m	88.89%	96.88%	248	< 0.0001	24.25 - 2,536.38
SOX1^m	77.78%	96.88%	108.5	< 0.0001	12.16 - 967.80
PAX1^m + SOX1^m	88.89%	93.75%	120	< 0.0001	18.53 - 777.02

Table 4. Sensitivity, Specificity, and Odds Ratios (ORs) of HPV Detection, PAX1 Methylation Detection, and SOX1 Methylation Detection in 139 Patients

Sensitivity

Specificity

95% CI

Inflammation/LSIL

HPV

63.33%

93.75%

25.91

< 0.0001

5.17 - 129.94

PAX1^m

10.00%

96.88%

3.44

0.27

0.34 - 35.09

SOX1^m

10.00%

96.88%

3.44

0.27

0.34 - 35.09

PAX1^m + SOX1^m

13.33%

93.75%

2.31

0.35

0.39 - 13.64

Inflammation/HSIL

HPV

92.00%

93.75%

172.5

< 0.0001

29.72 - 1,001.24

PAX1^m

44.00%

96.88%

24.36

< 0.0001

3.08 - 192.67

SOX1^m

40.00%

96.88%

20.67

< 0.0001

2.61 - 163.80

PAX1^m + SOX1^m

52.00%

93.75%

16.25

< 0.0001

3.50 - 75.43

Inflammation/CSCC

HPV

88.89%

93.75%

120

< 0.0001

18.53 - 777.02

PAX1^m

88.89%

96.88%

248

< 0.0001

24.25 - 2,536.38

SOX1^m

77.78%

96.88%

108.5

< 0.0001

12.16 - 967.80

PAX1^m + SOX1^m

88.89%

93.75%

120

< 0.0001

18.53 - 777.02