Characterization of integrin αL methylation in peripheral blood mononuclear cells from colon cancer patients with sepsis

doi:10.3877/cma.j.issn.1674-1358.2025.05.003

Abstract

Abstract:

Objective

To investigate the methylation characteristics of the integrin αL (ITGAL) promoter region in peripheral blood mononuclear cells (PBMCs) and its diagnostic value in patients with colon cancer complicated with sepsis.

Methods

Total of 209 patients initially diagnosed with colon cancer in the Second People’s Hospital of Nantong from March 1st, 2022 to March 31st, 2023 were selected and divided into simple colon cancer group (117 cases) and colon cancer with sepsis group (92 cases) based on the presence of sepsis complications, while 50 healthy subjects were selected as control group. The methylation levels at seven sites of the ITGAL promoter region in peripheral blood were analyzed by methylation-specific polymerase chain reaction (MSP). The levels of procalcitonin (PCT), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) of patients in both groups were detected by Chemiluminescence method and compared by one-way ANOVA among multiple groups. The diagnostic value of various indicators for sepsis of patients with colon cancer were evaluated by receiver operating characteristic (ROC) curves. The associations of gender, age, pathological grade, TNM stage, treatment method, PCT, IL-6, neutrophil-to-lymphocyte ratio (NLR) and ITGAL levels with the risk of sepsis in patients with colon cancer were analyzed by multivariate Logistic regression models.

Results

The methylation levels at ITGAL sites 40, 128 and 342 were significantly higher of patients in colon cancer with sepsis group compared with simple colon cancer group (t=3.69, 2.51, 4.76, P=0.017, 0.032, 0.010), but the methylation level at ITGAL-310 was significantly lower (t=5.19, P < 0.001), all with significant differences. The combined diagnosis of PCT, NLR, IL-6 and TNF-α showed the highest area under ROC curve (0.902), followed by PCT (0.857), ITGAL (0.842) and IL-6 (0.783). Multivariate Logistic regression analysis showed that age (OR=1.075, 95%CI: 1.022-1.060, P=0.041), TNM stage (OR=1.056, 95%CI: 1.009-9.894, P=0.047), treatment method (OR=3.933, 95%CI: 1.482-10.442, P=0.006), PCT (OR=1.353, 95%CI: 0.002-6.818, P=0.031) and ITGAL (OR=2.014, 95%CI: 0.000-5.726, P=0.014) were all influencing factors of the occurrence of sepsis in patients with colon cancer.

Conclusions

ITGAL and inflammatory factors are involved in the progression of sepsis in colon cancer and serve as sensitive biomarkers for the diagnosis of colon cancer-associated sepsis. PBMC-ITGAL methylation has discriminative diagnostic significance for colon cancer complicated with sepsis.

Key words: Colon cancer, Sepsis, Peripheral blood mononuclear cell, Integrin alpha L, Procalciton

Wei Zhang, Mingliang Shao, Jianhua Sun, Shirong Dai, Jinna Wu. Characterization of integrin αL methylation in peripheral blood mononuclear cells from colon cancer patients with sepsis[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2025, 19(05): 271-278.

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https://zhsyhlcgrbzz.cma-cmc.com.cn/EN/Y2025/V19/I05/271

Figures/Tables 6

引物名称	引物序列（5′→3′）	引物长度（bp）
S1-MF	GTTATTGGAGAAATGTTTATTTAAATC	141
S1-MR	TCTCACCATTACATTCCAACCT
S1-UF	GTTATTGGAGAAATGTTTATTTAAATT	141
S1-UR	TCTCACCATTACATTCCAACCT
S2-MF	GGTTATTTATATGTTATTGGAGAAATG	148
S2-MR	CCATTACATTCCAACCTAAACG
S2-UF	GGTTATTTATATGTTATTGGAGAAATG	149
S2-UR	ACCATTACATTCCAACCTAAACA
S3-MF	TAAGTAGTTGGGATTATAGGTATGC	160
S3-MR	CACACCTCTAATCCTAACCCTATA
S3-UF	TTAAGTAGTTGGGATTATAGGTATGT	161
S3-UR	CACACCTCTAATCCTAACCCTATA
S4-MF	TTAGGTTGGAATGTAATGGTGAGA	140
S4-MR	CAAAAATACAAAAATTAACCAAACG
S4-UF	TTAGGTTGGAATGTAATGGTGAGA	141
S4-UR	CCAAAAATACAAAAATTAACCAAACA
S5-MF	GTTAATTTTTGTATTTTTGGTAGAGAC	122
S5-MR	CACACCTCTAATCCTAACCCTATA
S5-UF	GTTAATTTTTGTATTTTTGGTAGAGAT	122
S5-UR	CACACCTCTAATCCTAACCCTATA
S6-MR	AAATCACCTAAAATCAAAAATTCG
S6-UF	TTTTTAAGTAGTTGGGATTATAGGTAT	125
S6-UR	TAAATCACCTAAAATCAAAAATTCA
S7-MF	TTTTTAAGTAGTTGGGATTATAGGTAT	155
S7-MR	AATCCTAACCCTATAAAAAACCG
S7-UF	TTTTTAAGTAGTTGGGATTATAGGTAT	156
S7-UR	TAATCCTAACCCTATAAAAAACCA

指标	单纯结肠癌组（117例）	结肠癌合并脓毒症组（92例）	统计量	P值
年龄（ $x ¯$ ±s，岁）	67.42±0.13	69.13±0.15	t=0.81	0.605
性别（男/女，例）	84/33	71/21	χ²=1.02	0.924
临床分期 [例（%）]
Ⅰ～Ⅱ	39（18.66）	42（20.09）	χ²=1.18	0.803
Ⅲ～Ⅳ	78（37.32）	50（23.93）	χ²=1.06	0.905
病理分级 [例（%）]
高分化	38（18.18）	32（15.31）	χ²=1.49	0.624
中分化	37（17.70）	31（14.83）	χ²=1.51	0.616
低分化	42（20.09）	29（13.88）	χ²=1.74	0.551
治疗方式 [例（%）]
手术切除	74（35.41）	60（28.71）	χ²=1.14	0.813
化疗	43（20.57）	32（15.31）	χ²=1.02	0.914

指标	单纯结肠癌组（117例）	结肠癌合并脓毒症组（92例）	统计量	P值
年龄（ $x ¯$ ±s，岁）	67.42±0.13	69.13±0.15	t=0.81	0.605
性别（男/女，例）	84/33	71/21	χ²=1.02	0.924
临床分期 [例（%）]
Ⅰ～Ⅱ	39（18.66）	42（20.09）	χ²=1.18	0.803
Ⅲ～Ⅳ	78（37.32）	50（23.93）	χ²=1.06	0.905
病理分级 [例（%）]
高分化	38（18.18）	32（15.31）	χ²=1.49	0.624
中分化	37（17.70）	31（14.83）	χ²=1.51	0.616
低分化	42（20.09）	29（13.88）	χ²=1.74	0.551
治疗方式 [例（%）]
手术切除	74（35.41）	60（28.71）	χ²=1.14	0.813
化疗	43（20.57）	32（15.31）	χ²=1.02	0.914

指标	对照组（50例）	单纯结肠癌组（117例）	结肠癌合并脓毒症组（92例）	F值	P值
甲基化水平（%）
ITGAL-40	12.14±1.02	23.37±1.52	36.60±1.46	3.69	0.017
ITGAL-128	18.25±0.69	20.07±1.15	33.15±1.19	2.51	0.030
ITGAL-238	11.20±1.03	13.18±1.34	15.04±0.84	0.53	0.070
ITGAL-246	10.47±1.21	15.28±1.05	13.62±1.42	0.16	0.091
ITGAL-278	18.32±0.48	30.19±1.26	29.48±0.52	1.64	0.057
ITGAL-310	11.93±0.55	40.16±1.26	23.52±1.24	5.19	0.001
ITGAL-342	20.05±0.75	34.29±0.61	44.19±0.94	4.76	0.010
炎症因子
PCT（pg/ml）	0.04±0.01	2.85±0.53	7.19±0.12	1.82	0.042
TNF-α（pg/ml）	1.5 3±0.24	4.72±0.39	13.49±0.54	2.16	0.040
IL-6（ng/ml）	3.10±0.21	16.04±0.83	5.32±0.21	0.84	0.051
NLR	1.15±0.01	3.74±0.51	1.42±0.47	3.57	0.682

指标	Cut-off值	灵敏度（%）	特异度（%）	准确率（%）	AUC
ITGAL	2.40	73.52	76.07	78.90	0.783
TNF-α	2.03	81.97	72.74	62.03	0.909
IL-6	0.57	89.33	39.21	72.67	0.657
PCT	4.31	52.17	61.17	63.81	0.590
NLR	0.97	46.16	76.47	39.11	0.662
联合诊断	—	89.60	78.23	82.09	0.939

影响因素	β值	S.E.值	Wald χ²值	OR值	95%CI	P值
性别	0.424	0.517	3.144	0.533	0.372～1.339	0.621
年龄	0.040	0.442	11.375	1.075	1.022～1.060	0.041
病理分级	0.598	0.483	2.482	0.818	0.687～4.809	0.228
TNM分期	2.403	0.374	10.264	1.056	1.009～9.894	0.047
治疗方式	1.370	0.522	9.574	3.933	1.482～10.442	0.006
PCT	3.027	0.506	5.024	1.353	0.002～6.818	0.031
IL-6	0.404	0.371	3.953	0.041	0.103～9.514	0.314
NLR	0.108	0.491	1.182	0.897	0.587～1.373	0.687
ITGAL	－4.245	0.513	7.361	2.014	0.000～5.726	0.014
TNF-α	0.042	0.406	1.453	0.048	0.000～11.294	0.428

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