IL-37b与TNF-α在大肠癌患者中的关系及其临床意义
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摘要
目的通过检测大肠癌患者血浆中白细胞介素(IL)-37b和肿瘤坏死因子-α(TNF-α)的水平,探讨IL-37b与大肠癌的发生、发展的关系。方法利用酶联免疫吸附试验(ELISA)对30例大肠癌患者和13例健康对照者血浆IL-37b和TNF-α水平进行检测,并对15例术后患者和10例放化疗患者血浆进行了治疗后的跟踪检测。结果大肠癌患者血浆IL-37b水平高于健康对照者,差异有统计学意义(P<0.05);患者血浆IL-37b水平与TNF-α水平呈负相关关系;患者癌组织病理分级分组比较显示,分化低的患者血浆IL-37b水平较分化高的患者增高,TNM分期Ⅳ期高于临床分期Ⅰ期,差异有统计学意义(P<0.05);TNF-α在肿瘤细胞分化高的患者中水平高于分化低的患者,临床分期Ⅰ期高于临床分期Ⅳ期,差异有统计学意义(P<0.05);患者在放化疗前后血浆IL-37b与TNF-α水平差异无统计学意义(P>0.05),术后患者血浆IL-37b水平下降,TNF-α水平增高。结论 IL-37b在大肠癌患者血浆中水平增高,并与大肠癌的病理分级及临床分期相关,与疾病的转归相关;IL-37b水平与TNF-α水平呈负相关关系,IL-37b可能通过调节TNF-α影响大肠癌的发展;IL-37b可能作为大肠癌的预后的辅助诊断指标。
Objective To detect the plasma interleukin(IL)-37 band tumor necrosis factor-α(TNF-α)level in patients with colorectal cancer and explore the relationship with the occurrence and development of colorectal cancer.Methods Plasma IL-37 band TNF-αlevel from 30 patients with colorectal cancer and 13 healthy controls were detected by enzyme-linked immunosorbent assay(ELISA),15 patients after surgical intervention and 10 patients after chemoradiotherapy were followed-up.Results The plasma IL-37 blevel in patients with colorectal cancer was higher than that in controls,and the difference was statistically significant(P<0.05).The plasma IL-37 blevel was negative correlation with the level of TNF-αinpatients with colorectal cancer.According to the comparisons of histopathological grading and grouping of patients with cancer,the plasma IL-37 blevel in the patients with low differentiation was significantly higher than that in high differentiation,and the plasma IL-37 blevel in the patients with the clinical TNM stage Ⅳ was significantly higher than that in the patients with clinical stageⅠ,and the difference was statistically significant(P<0.05).The plasma TNF-αlevel in the patients with high differentiation was significantly higher than that in the patients with low differentiation,and plasma TNF-αlevel in the patients with the clinical stageⅠ was higher than that in the patients with the clinical stageⅣ,and the difference was statistically significant(P<0.05).There was no difference between plasma IL-37 band TNF-αlevels before and after chemoradiotherapy,but plasma IL-37 b was significantly decreased and TNF-αlevels were significantly increased after operation.Conclusion The plasma IL-37 blevel was increased in patients with colorectal cancer,and was correlated with the pathological grade,clinical stage and prognosis of colorectal cancer.The level of IL-37 b is negatively correlated with the level of TNF-α,IL-37 bmay influence the development of colorectal cancerthrough regulating the TNF-αand it may be used as an auxiliary diagnostic index for the prognosis of colorectal cancer.
Objective To detect the plasma interleukin(IL)-37 band tumor necrosis factor-α(TNF-α)level in patients with colorectal cancer and explore the relationship with the occurrence and development of colorectal cancer.Methods Plasma IL-37 band TNF-αlevel from 30 patients with colorectal cancer and 13 healthy controls were detected by enzyme-linked immunosorbent assay(ELISA),15 patients after surgical intervention and 10 patients after chemoradiotherapy were followed-up.Results The plasma IL-37 blevel in patients with colorectal cancer was higher than that in controls,and the difference was statistically significant(P<0.05).The plasma IL-37 blevel was negative correlation with the level of TNF-αinpatients with colorectal cancer.According to the comparisons of histopathological grading and grouping of patients with cancer,the plasma IL-37 blevel in the patients with low differentiation was significantly higher than that in high differentiation,and the plasma IL-37 blevel in the patients with the clinical TNM stage Ⅳ was significantly higher than that in the patients with clinical stageⅠ,and the difference was statistically significant(P<0.05).The plasma TNF-αlevel in the patients with high differentiation was significantly higher than that in the patients with low differentiation,and plasma TNF-αlevel in the patients with the clinical stageⅠ was higher than that in the patients with the clinical stageⅣ,and the difference was statistically significant(P<0.05).There was no difference between plasma IL-37 band TNF-αlevels before and after chemoradiotherapy,but plasma IL-37 b was significantly decreased and TNF-αlevels were significantly increased after operation.Conclusion The plasma IL-37 blevel was increased in patients with colorectal cancer,and was correlated with the pathological grade,clinical stage and prognosis of colorectal cancer.The level of IL-37 b is negatively correlated with the level of TNF-α,IL-37 bmay influence the development of colorectal cancerthrough regulating the TNF-αand it may be used as an auxiliary diagnostic index for the prognosis of colorectal cancer.
引文
[1]CHEN W Q,ZHENG R S,ZENG H M,et al.The updated incidences and mortalities of major cancers in China,2011[J].Chin J Cancer,2015,34(3):502-507.
[2]李奕,邰升.大肠癌肝转移治疗进展[J/CD].中华结直肠疾病电子杂志,2017,6(3):238-242.
[3]SMITH D E,RENSHAW B R,KETCHEM R R,et al.Four new members expand the interleukin-1superfamily[J].J Biol Chem,2000,275(2):1169-1175.
[4]QUIRK S,AGRAWAL D K.Immunobiology of IL-37:mechanism of action and clinical perspectives[J].Expert Rev Clin Immunol,2014,10(12):1703-1709.
[5]JIANG M F,WANG Y,ZHANG H,et al.IL-37inhibits invasion and metastasis in non-small cell lung cancer by suppressing the IL-6/STAT3signaling pathway[J].Thoracic Cancer,2018,9(5):621-629.
[6]LIU R,TANG C,SHEN A,et al.IL-37suppresses hepatocellular carcinoma growth by converting pSmad3signaling from JNK/pSmad3L/c-Myc oncogenic signaling to pSmad3C/P21tumor-suppressive signaling[J].Oncotarget,2016,7(51):85079-85096.
[7]ABULKHIR A,SAMARANI S,AMRE D,et al.A protective role of IL-37in cancer:a new hope for cancer patients[J].J Leukoc Biol,2017,101(2):395-406.
[8]CARINCI F,LESSIANI G,SPINAS E,et al.Mast cell and cancer with special emphasis on il-37an anti-inflammatory and inhibitor of innate immunity:new frontiers[J].J Biol Regul Homeost Agents,2016,30(4):945-950.
[9]SENOVILLA L,GALLUZZI L,ZITVOGEL L A.Immunosurveillance as a regulator of tissue homeostasis[J].Trends Immunol,2013,34(10):471-481.
[10]CAVALLI G,DINARELLO C A.Suppression of inflammation and acquired immunity by IL-37[J].Immunol Rev,2018,281(1):179-190.
[11]RUDLOFF I,CHO S X,LAO J C,et al.Monocytes and dendritic cells are the primary sources of interleukin 37in human immune cells[J].J Leukoc Biol,2017,101(4):901-911.
[12]LI T T,ZHU D,MOU T,et al.IL-37induces autophagy in hepatocellular carcinoma cells by inhibiting the PI3K/AKT/mTOR pathway[J].Mol Immunol,2017,87:132-140.
[13]GUNALTAY S,GHIBOUB M,HULTGREN O,et al.Reduced IL-37production increases spontaneous chemokine expressions in colon epithelial cells[J].Dig Dis Sci,2017,62(5):1204-1215.
[14]CONTI P,CARAFFA A,RONCONI G,et al.Impact of mast cells in mucosal immunity of intestinal inflammation:Inhibitory effect of IL-37[J].Eur J Pharmacol,2018,818(4):294-299.
[15]BERRAONDO P,TEIJEIRA A,MELERO I.Cancer immunosurveillance caught in the act[J].Immunity,2016,44(3):525-526.
[16]ZHAO M M,HU Y G,SHOU J J,et al.IL-37impairs host resistance to Listeria infection by suppressing macrophage function[J].Biochem Biophys Res Commun,2017,485(2):563-568.
[17]LUO Y C,CAI X N,LIU S C,et al.Suppression of antigen-specific adaptive immunity by IL-37via induction of tolerogenic dendritic cells[J].Proc Natl Acad Sci U S A,2014,111(42):15178-15183.
[18]ZHANG J A,LIU G B,ZHENG B Y,et al.Tuberculosissensitized monocytes sustain immune response of interleukin-37[J].Mol Immunol,2016,79(9):14-21.
[19]ZHU R R,SUN H T,YU K W,et al.Interleukin-37and dendritic cells treated with interleukin-37plus troponin Iameliorate cardiac remodeling after myocardial infarction[J].J Am Heart Assoc,2016,5(12):e004406.
[20]SCHAUER A E,KLASSERT T E,VON LACHNER CA,et al.IL-37causes excessive inflammation and tissue damage on murine pneumococcal pneumonia[J].J Innate Immun,2017,9(4):403-418.
[2]李奕,邰升.大肠癌肝转移治疗进展[J/CD].中华结直肠疾病电子杂志,2017,6(3):238-242.
[3]SMITH D E,RENSHAW B R,KETCHEM R R,et al.Four new members expand the interleukin-1superfamily[J].J Biol Chem,2000,275(2):1169-1175.
[4]QUIRK S,AGRAWAL D K.Immunobiology of IL-37:mechanism of action and clinical perspectives[J].Expert Rev Clin Immunol,2014,10(12):1703-1709.
[5]JIANG M F,WANG Y,ZHANG H,et al.IL-37inhibits invasion and metastasis in non-small cell lung cancer by suppressing the IL-6/STAT3signaling pathway[J].Thoracic Cancer,2018,9(5):621-629.
[6]LIU R,TANG C,SHEN A,et al.IL-37suppresses hepatocellular carcinoma growth by converting pSmad3signaling from JNK/pSmad3L/c-Myc oncogenic signaling to pSmad3C/P21tumor-suppressive signaling[J].Oncotarget,2016,7(51):85079-85096.
[7]ABULKHIR A,SAMARANI S,AMRE D,et al.A protective role of IL-37in cancer:a new hope for cancer patients[J].J Leukoc Biol,2017,101(2):395-406.
[8]CARINCI F,LESSIANI G,SPINAS E,et al.Mast cell and cancer with special emphasis on il-37an anti-inflammatory and inhibitor of innate immunity:new frontiers[J].J Biol Regul Homeost Agents,2016,30(4):945-950.
[9]SENOVILLA L,GALLUZZI L,ZITVOGEL L A.Immunosurveillance as a regulator of tissue homeostasis[J].Trends Immunol,2013,34(10):471-481.
[10]CAVALLI G,DINARELLO C A.Suppression of inflammation and acquired immunity by IL-37[J].Immunol Rev,2018,281(1):179-190.
[11]RUDLOFF I,CHO S X,LAO J C,et al.Monocytes and dendritic cells are the primary sources of interleukin 37in human immune cells[J].J Leukoc Biol,2017,101(4):901-911.
[12]LI T T,ZHU D,MOU T,et al.IL-37induces autophagy in hepatocellular carcinoma cells by inhibiting the PI3K/AKT/mTOR pathway[J].Mol Immunol,2017,87:132-140.
[13]GUNALTAY S,GHIBOUB M,HULTGREN O,et al.Reduced IL-37production increases spontaneous chemokine expressions in colon epithelial cells[J].Dig Dis Sci,2017,62(5):1204-1215.
[14]CONTI P,CARAFFA A,RONCONI G,et al.Impact of mast cells in mucosal immunity of intestinal inflammation:Inhibitory effect of IL-37[J].Eur J Pharmacol,2018,818(4):294-299.
[15]BERRAONDO P,TEIJEIRA A,MELERO I.Cancer immunosurveillance caught in the act[J].Immunity,2016,44(3):525-526.
[16]ZHAO M M,HU Y G,SHOU J J,et al.IL-37impairs host resistance to Listeria infection by suppressing macrophage function[J].Biochem Biophys Res Commun,2017,485(2):563-568.
[17]LUO Y C,CAI X N,LIU S C,et al.Suppression of antigen-specific adaptive immunity by IL-37via induction of tolerogenic dendritic cells[J].Proc Natl Acad Sci U S A,2014,111(42):15178-15183.
[18]ZHANG J A,LIU G B,ZHENG B Y,et al.Tuberculosissensitized monocytes sustain immune response of interleukin-37[J].Mol Immunol,2016,79(9):14-21.
[19]ZHU R R,SUN H T,YU K W,et al.Interleukin-37and dendritic cells treated with interleukin-37plus troponin Iameliorate cardiac remodeling after myocardial infarction[J].J Am Heart Assoc,2016,5(12):e004406.
[20]SCHAUER A E,KLASSERT T E,VON LACHNER CA,et al.IL-37causes excessive inflammation and tissue damage on murine pneumococcal pneumonia[J].J Innate Immun,2017,9(4):403-418.