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中华实验和临床感染病杂志(电子版) ›› 2025, Vol. 19 ›› Issue (05) : 271 -278. doi: 10.3877/cma.j.issn.1674-1358.2025.05.003

论著

结肠癌脓毒症患者外周血单个核细胞整合素αL甲基化特征
张巍1, 邵明亮1,†(), 孙建华1, 戴世荣1, 吴金娜2   
  1. 1　226000　南通市，南通市第二人民医院检验科
    2　226300　南通市，南通市中医院乳腺外科
  • 收稿日期:2025-04-08 出版日期:2025-10-15
  • 通信作者: 邵明亮
  • 基金资助:
    江苏省中医药发展计划项目(MS2022092)

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

Wei Zhang1, Mingliang Shao1,†(), Jianhua Sun1, Shirong Dai1, Jinna Wu2   

  1. 1 Department of Laboratory Medicine, The Second People’s Hospital of Nantong, Nantong 226000, China
    2 Department of Breast Surgery, Nantong Hospital of Traditional Chinese Medicine, Nantong 226300, China
  • Received:2025-04-08 Published:2025-10-15
  • Corresponding author: Mingliang Shao
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引用本文：

张巍, 邵明亮, 孙建华, 戴世荣, 吴金娜. 结肠癌脓毒症患者外周血单个核细胞整合素αL甲基化特征[J/OL]. 中华实验和临床感染病杂志(电子版), 2025, 19(05): 271-278.

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/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2025, 19(05): 271-278.

目的

分析结肠癌并发脓毒症患者外周血单个核细胞（PBMC）整合素αL（ITGAL）启动子区域的甲基化特征及其诊断价值。

方法

选取南通市第二人民医院2022年3月1日～2023年3月31日初诊为结肠癌患者共209例，根据是否并发脓毒症分为单纯结肠癌组（117例）和结肠癌合并脓毒症组（92例）；选取同期健康体检者50例作为对照组。采用甲基化特异PCR（MSP）方法分析外周血ITGAL启动子区域7个位点的甲基化水平，采用化学发光法检测单纯结肠癌组和结肠癌并发脓毒症组患者降钙素原（PCT）、白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α表达水平，多组间比较行单因素方差分析。采用受试者工作特征（ROC）曲线分析各项指标对结肠癌患者并发脓毒症的诊断价值。采用多因素Logistic回归分析性别、年龄、病理分级、TNM分期、治疗方式、PCT、IL-6、NLR及ITGAL水平与结肠癌患者并发脓毒症风险的关联。

结果

结肠癌合并脓毒症组患者ITGAL40、128、342位点甲基化水平高于单纯结肠癌组（t=3.69、2.51、4.76，P=0.017、0.032、0.010），ITGAL-310位点甲基化低于单纯结肠癌组（t=5.19、P ＜ 0.001），差异均有统计学意义。PCT、NLR、IL-6和TNF-α联合诊断结肠癌患者并发脓毒症ROC曲线下面积（AUC）值最高（0.902），其次为PCT（0.857）、ITGAL（0.842）和IL-6（0.783）。多因素Logistic回归分析显示，年龄（OR=1.075、95%CI：1.022～1.060、P=0.041）、TNM分期（OR=1.056、95%CI：1.009～9.894、P=0.047）、治疗方式（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）和ITGAL（OR=2.014、95%CI：0.000～5.726、P=0.014）均为结肠癌患者发生脓毒症的影响因素。

结论

ITGAL与炎症因子参与结肠癌脓毒症进展，是诊断结肠癌发生脓毒症的敏感标志物。PBMC-ITGAL甲基化对结肠癌并发脓毒症具有鉴别诊断意义。

关键词: 结肠癌, 脓毒症, 外周血单个核细胞, 整合素αL, 降钙素原
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
表1 ITGAL甲基化引物设计
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
表2 单纯结肠癌组和结肠癌合并脓毒症组患者的一般资料、临床分期和病理分级
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（
±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
表3 单纯结肠癌组和结肠癌合并脓毒症组患者ITGAL甲基化和炎症因子水平（
±s）
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
图1 ITGAL和炎症因子以及各指标联合应用诊断结肠癌患者发生脓毒症的ROC曲线 注：图A～F分别表示ITGAL、IL-6、PCT、TNF-α、NLR以及各指标联合诊断结肠癌患者发生脓毒症ROC曲线
表4 ITGAL和TNF-α等炎症因子对结肠癌患者发生脓毒症的诊断价值
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
表5 结肠癌并发脓毒症影响因素的多因素Logistic回归分析
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
[1]
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2021,71(3):209-249
[2]
Wang SH, Chen YL, Huang SH, et al. Tumor cell-derived ISG15 promotes fibroblast recruitment in oral squamous cell carcinoma via CD11a-dependent glycolytic reprogramming[J]. Oncogenesis,2025,14(1):6.
[3]
Shadman H, Gomrok S, Litle C, et al. A machine learning-based investigation of integrin expression patterns in cancer and metastasis[J]. Sci Rep,2025,15(1):5270.
[4]
Bergqvist M, Park KS, Karimi N, et al. Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells[J]. J Nanobiotechnology,2025,23(1):64.
[5]
Nie LY, Zhao K, Xu C, et al. Identification of potential genes in rheumatoid arthritis-associated interstitial lung disease using RNA-seq and in vitro analyses[J]. Cell Biochem Funct,2025,43(1):e70033.
[6]
Lin FJ, Yang HX, Huang ZW, et al. Magnesium-related gene ITGAL: a key immunotherapy predictor and prognostic biomarker in pan-cancer[J]. Front Pharmacol,2024,15:1464830.
[7]
Veronez LC, Xavier AE, Nagano LF, et al. Identifying prognostic hub genes and key pathways in pediatric adrenocortical tumors through RNA sequencing and Co-expression analysis[J]. Mol Cell Endocrinol,2024,594:112383.
[8]
Liu BB, Fan YH, Zhang XJ, et al. Identification of immune-related genes as potential biomarkers in early septic shock[J]. Int Arch Allergy Immunol,2025,186(3):264-279.
[9]
Cheng J, Ji DR, Ma J, et al. Proteomic analysis of serum small extracellular vesicles identifies diagnostic biomarkers for neuroblastoma[J]. Front Oncol,2024,14:1367159.
[10]
Thierry GR, Baudon EM, Bijnen M, et al. Non-classical monocytes scavenge the growth factor CSF1 from endothelial cells in the peripheral vascular tree to ensure survival and homeostasis[J]. Immunity,2024,57(9):2108-2121. e6.
[11]
Chen LJ, Huang YQ, Zhang N, et al. Single-cell RNA sequencing reveals reduced intercellular adhesion molecule crosstalk between activated hepatic stellate cells and neutrophils alleviating liver fibrosis in hepatitis B virus transgenic mice post menstrual blood-derived mesenchymal stem cell transplantation[J]. Med Comm,2024,5(8):e654.
[12]
Lv JY, Shi SQ, Fu ZY, et al. Exploring the inflammation-related mechanisms of Lingguizhugan decoction on right ventricular remodeling secondary to pulmonary arterial hypertension based on integrated strategy using UPLC-HRMS, systems biology approach, and experimental validation[J]. Phytomedicine,2024,132:155879.
[13]
于欣睿, 曾辉. Janus激酶-信号转导与转录激活因子信号通路与脓毒症关系的复杂性[J/CD]. 中华实验和临床感染病杂志(电子版),2022,16(6):366-369.
[14]
Rabia I, Zaigham UI, Ahmad TB, et al. Prevalence and outcomes of sepsis in patients with colon carcinoma: organism-specific analysis[J]. Cureus,2024,16(11):e74175.
[15]
Natchaya P, Sakditad S, Aunchalee J, et al. Impact of colon cancer on outcomes in hospitalized patients with Clostridioides difficile infection: a national inpatient analysis[J]. Proc (Bayl Univ Med Cent),2024,37(4):544-550.
[16]
Yeung E, Biedrzycki RJ, Gómez HL, et al. Maternal age is related to offspring DNA methylation: A Meta-analysis of results from the PACE consortium[J]. Aging Cell,2024,23(8):e14194.
[17]
Potter SJ, Zhang L, Kotliar M, et al. KMT2D regulates activation, localization, and integrin expression by T-cells[J]. Front Immunol,2024,15:1341745.
[18]
Yang YT, Zhen B, Cao X, et al. Machine learning algorithm-based discovery of potential regulators of immune-related dilated cardiomyopathy[J]. Acta Cardiol Sin,2025,41(2):230-241.
[19]
Boccarelli A, Del BN, Esposito F, et al. Review of patient gene profiles obtained through a non-negative matrix factorization-based framework to determine the role inflammation plays in neuroblastoma pathogenesis[J]. Int J Mol Sci,2024,25(8):4406.
[20]
Zhang RH, Zhu GS, Li ZS, et al. ITGAL expression in non-small-cell lung cancer tissue and its association with immune infiltrates[J]. Front Immunol,2024,15:1382231.
[21]
边晓倩, 王莎莎, 赵淑芬, 等. Ⅲ期结直肠癌血清细胞因子水平与术后短期复发关系[J]. 青岛大学学报(医学版),2024,60(1):72-76.
[22]
Niu T, Li Z, Huang Y, et al. LFA-1 knockout inhibited the tumor growth and is correlated with treg cells[J]. Cell Commun Signal,2023,21:233.
[23]
Martin TM, Burke SJ, Wasserfall CH, Collier JJ. Islet beta-cells and intercellular adhesion molecule-1 (ICAM-1): Integrating immune responses that influence autoimmunity and graft rejection[J]. Autoimmun Rev,2023,22(10):103414.
[24]
Hickman A, Koetsier J, Kurtanich T, et al. LFA-1 activation enriches tumor-specific T cells in a cold tumor model and synergizes with CTLA-4 blockade[J]. J Clin Invest,2022,132(13):e154152.
[25]
De Andrade CA, Chatterjee J, Cobb O, et al. RNA sequence analysis reveals ITGAL/CD11A as a stromal regulator of murine low-grade glioma growth[J]. Neuro Oncol,2022,24(1):14-26.
[26]
Chinchilla-Tábora LM, Montero JC, Corchete LA, et al. Differentially expressed genes involved inprimary resistance to immunotherapy in patients with advanced-stage pulmonarycancer[J]. Int J Mol Sci,2024,25(4):2048.
[27]
陈莉莉, 吴天宇, 张铭, 等. 类风湿关节炎的潜在生物标志物及其免疫调控机制[J]. 南方医科大学学报,2024,44(6):1098-1108
[28]
Li C, Zhang L, Zhang L, et al. Correlation between elevated HCLS1 levels and heart failure: A diagnostic biomarker[J]. Medicine (Baltimore),2024,103(23):e38484.
[29]
Xie B, Wu T, Hong D, et al. Comprehensive landscape of junctional genes and their association with overall survival of patients with lung adenocarcinoma[J]. Front Mol Biosci,2024,11:1380384.
[30]
Wang HJ, Zhou CJ. Occult colon cancer with sepsis as the primary manifestation identified by bone marrow puncture: A case report[J]. World J Clin Cases,2022,10(9):2969-2975.
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