结直肠癌患者术前焦虑状态与细胞因子水平变化关系的研究
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摘要
目的:探究结直肠癌(colorectal cancer,CRC)患者术前焦虑状态与血浆细胞因子水平变化的关系。方法:选取结直肠癌患者93名,采用汉密尔顿焦虑量表(Hamilton Rating Scale for Anxiety,HAMA)、纽芬兰纪念大学主观幸福感量表(Memorial University of Newfoundland Scale of Happiness,MUNSH)、癌症患者生命质量测定量表(Quality of Life Questionnaire,QLQ-C30)、自尊量表(self-esteem scale,SES)评估患者身心健康状况,根据HAMA评分将CRC患者分为三组:HAMA<7(无焦虑组)42人,7≤HAMA<14(可能焦虑组)30人,HAMA≥14(焦虑组)21人。用LUMINEX(悬液芯片技术)检测各组血浆G-CSF、GM-CSF、IL-2、IL-6、IL-8、IL-10、IL-12p70、IL-13、IL-17A、IL-1β、MCP-1、TNF-α、IFN-γ水平。结果:无焦虑组和可能焦虑组、焦虑组的MUNSH、SES、QLQ-C30总分的差异均有统计学意义(P<0.05),可能焦虑组和焦虑组MUNSH、SES、QLQ-C30总分的差异无统计学意义(P>0.05)。三组CRC患者的G-CSF、GM-CSF、IL-2、IL-6、IL-8、IL-10、IL-12p70、IL-1β、MCP-1、TNF-α、IFN-γ随HAMA分值的增高存在相似的倒"V"型变化趋势:细胞因子在HAMA<7组水平最低,在7≤HAMA<14组水平最高,在HAMA>14组较前者出现下降,但仍高于HAMA<7组(IL-1β除外)。G-CSF(P=0.017、IL-10(P=0.035)、IL-12p70(P=0.047)、IFN-γ(P=0. 029)在三组之间的差异有统计学意义。结论:不同焦虑程度的结直肠癌患者外周血中的细胞因子水平有所不同,可能焦虑组的结直肠癌患者同样需要临床和科研工作者的重视。
Objective: To explore the association between anxiety and inflammatory cytokine levels in colorectal cancer(CRC) patients.Methods:Ninety-three colorectal cancer(CRC)patients were assessed by The Hamilton Rating Scale for Anxiety(HAMA),Memorial University of Newfoundland Scale of Happiness(MUNSH),Quality of Life Questionnaire(QLQ-C30)and self-esteem scale(SES) to measure the psychological and physical wellbeing.CRC patients were classified into three groups:HAMA<7(non-anxiety),7≤HAMA<14(possible anxiety),and HAMA≥14(anxiety).LUMINEX was conducted to quantify the inflammatory cytokines G-CSF,GM-CSF,IL-2,IL-6,IL-8,IL-10,IL-12 p70,IL-13,IL-17 A,IL-1β,MCP-1,TNF-α,and IFN-γ in the plasma.Results:The total scores of MUNSH,SES,and QLQ-C30 of the non-anxiety group were significantly different from the possible anxiety group and the anxiety group(P<0.05).The total scores of MUNSH,SES,and QLQ-C30 of the possible anxiety group were not significantly different from the anxiety group(P>0.05).There was a similar inverted "V" trend in G-CSF,GM-CSF,IL-2,IL-6,IL-8,IL-10,IL-12 p70,IL-1β,MCP-1,TNF-α,IFN-γ with the increase of HAMA score in CRC groups:Cytokines were the lowest in HAMA<7 group and highest in 7≤HAMA<14 group respectively,with HAMA>14 group decreased despite its higher than HAMA<7 group(except for IL-1β).The CRC groups differed statistically significant in G-CSF(P=0.017),IL-10(P=0.035),IL-12 p70(P=0.047),and IFN-γ(P=0.029).Conclusion:The levels of cytokines may be different in CRC patients with different degrees of anxiety and we may need to focus on the possible anxiety patients.
Objective: To explore the association between anxiety and inflammatory cytokine levels in colorectal cancer(CRC) patients.Methods:Ninety-three colorectal cancer(CRC)patients were assessed by The Hamilton Rating Scale for Anxiety(HAMA),Memorial University of Newfoundland Scale of Happiness(MUNSH),Quality of Life Questionnaire(QLQ-C30)and self-esteem scale(SES) to measure the psychological and physical wellbeing.CRC patients were classified into three groups:HAMA<7(non-anxiety),7≤HAMA<14(possible anxiety),and HAMA≥14(anxiety).LUMINEX was conducted to quantify the inflammatory cytokines G-CSF,GM-CSF,IL-2,IL-6,IL-8,IL-10,IL-12 p70,IL-13,IL-17 A,IL-1β,MCP-1,TNF-α,and IFN-γ in the plasma.Results:The total scores of MUNSH,SES,and QLQ-C30 of the non-anxiety group were significantly different from the possible anxiety group and the anxiety group(P<0.05).The total scores of MUNSH,SES,and QLQ-C30 of the possible anxiety group were not significantly different from the anxiety group(P>0.05).There was a similar inverted "V" trend in G-CSF,GM-CSF,IL-2,IL-6,IL-8,IL-10,IL-12 p70,IL-1β,MCP-1,TNF-α,IFN-γ with the increase of HAMA score in CRC groups:Cytokines were the lowest in HAMA<7 group and highest in 7≤HAMA<14 group respectively,with HAMA>14 group decreased despite its higher than HAMA<7 group(except for IL-1β).The CRC groups differed statistically significant in G-CSF(P=0.017),IL-10(P=0.035),IL-12 p70(P=0.047),and IFN-γ(P=0.029).Conclusion:The levels of cytokines may be different in CRC patients with different degrees of anxiety and we may need to focus on the possible anxiety patients.
引文
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[24] Santos JC,Pyter LM.Neuroimmunology of behavioral comorbidities associated with cancer and cancer treatments[J].Frontiers in Immunology,2018,9:17.
[25] Leonard BE,Myint A.The psychoneuroimmunology of depression[J].Human Psychopharmacol-Clin Exp,2009,24(3):165-175.
[26] Hou R,Baldwin DS.A neuroimmunological perspective on anxiety disorders[J].Hum Psychopharmacol,2012,27(1):6-14.
[27] Arranz L,Guayerbas N,De la Fuente M.Impairment of several immune functions in anxious women[J].J Psychosomatic Res,2007,62(1):1-8.
[28] Lutgendorf SK,Lamkin DM,DeGeest K,et al.Depressed and anxious mood and T-cell cytokine expressing populations in ovarian cancer patients[J].Brain Behav Immun,2008,22(6):890-900.
[29] Takkouche B,Regueira C,Gestal-Otero JJ.A cohort study of stress and the common cold[J].Epidemiology,2001,12(3):345-349.
[30] Huang YQ,Wang ZF,Zhou WP,et al.The changes and clinical significance of IL-6,TNF-α and CRP levels in patients with colorectal cancer[J].Oncolory Progress,2018,16(9):1140-1142.[黄有群,王振奋,周卫平.结直肠癌患者 IL-6、TNF-α、CRP 的水平变化特点及临床意义[J].癌症进展,2018,16(9):1140-1142.]
[31] Yang Y,Tian M.Relationship between TNF-α,IL-6 and IL-8 levels and clinical stage in patients with colorectal cancer[J].Labeled Immunoassays and Clin Med,2016,23(7):790-793.[杨勇,田敏.结直肠癌患者TNF-α、IL-6、IL-8水平与临床分期的关系与研究[J].标记免疫分析与临床,2016,23(7):790-793.]
[2] Bektas DK,Demir S.Anxiety,depression levels and quality of life in patients with gastrointestinal cancer in turkey[J].Asian Pacific Journal of Cancer Prevention,2016,17(2):723-731.
[3] Escobar A,Billbao A,Trancho Z,et al.Influence of anxiety and depression on 1-year health related quality of life in colorectal cancer patients[J].Value in Health,2013,16(7):A421-A422.
[4] Hong JS,Tian J.Prevalence of anxiety and depression and their risk factors in Chinese cancer patients[J].Support Care Cancer,2014,22(2):453-459.
[5] Miranda DO,Soares de Lima TA,Ribeiro Azevedo L,et al.Proinflammatory cytokines correlate with depression and anxiety in colorectal cancer patients[J].Biomed Res Int,2014,2014:1-5.
[6] Sotelo JL,Musselman D,Nemeroff C.The biology of depression in cancer and the relationship between depression and cancer progression[J].Int Rev Psychiatry,2014,26(1):16-30.
[7] Miller AH,Ancoli-Israel S,Bower JE,et al.Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer[J].J Clin Oncol,2008,26(6):971-982.
[8] Hou R,Garner M,Holmes C,et al.Peripheral inflammatory cytokines and immune balance in generalised anxiety disorder:Case-controlled study[J].Brain Behav Immun,2017,62:212-218.
[9] Miranda DO,Anatriello E,Azevedo LR,et al.Elevated serum levels of proinflammatory cytokines potentially correlate with depression and anxiety in colorectal cancer patients in different stages of the antitumor therapy[J].Cytokine,2018,104:72-77.
[10] Sepah SC,Bower JE.Positive affect and inflammation during radiation treatment for breast and prostate cancer[J].Brain Behavior and Immunity,2009,23(8):1068-1072.
[11] Bower JE,Ganz PA,Aziz N,et al.Fatigue and proinflammatory cytokine activity in breast cancer survivors[J].Psychosomatic Medicine,2002,64(4):604-611.
[12] Maier W,Buller R,Philipp M,et al.The Hamilton Anxiety Scale:Reliability,validity and sensitivity to change in anxiety and depressive disorders[J].J Affective Disorders,1988,14(1):61-68.
[13] Zhang MY,He YL.Hamilton Anxiety Scale[M].Hunan:Hunan Science and Technology Press,2015:181-183.[张明圆,何燕玲.汉密尔顿焦虑量表[M].湖南:湖南科学技术出版社,2015:181-183.]
[14] Dirksen SR,Kirschner KF,Belyea MJ.Association of symptoms and cytokines in prostate cancer patients receiving radiation treatment[J].Biol Res Nursing,2014,16(3):250-257.
[15] Lutgendorf SK,Lamkin DM,DeGeest K,et al.Depressed and anxious mood and T-cell cytokine expressing populations in ovarian cancer patients[J].Brain Behavior and Immunity,2008,22(6):890-900.
[16] Pyter LM,Suarez-Kelly LP,Carson WE,et al.Novel rodent model of breast cancer survival with persistent anxiety-like behavior and inflammation[J].Behavioural Brain Res,2017,330:108-117.
[17] Kim SY,Kim JM,Kim SW,et al.Associations between plasma cytokines and depressive mood in patients with breast cancer[J].Int J Psychiatry Med,2012,43(1):1-17.
[18] Young JJ,Bruno D,Pomara N.A review of the relationship between proinflammatory cytokines and major depressive disorder[J].J Affect Disord,2014,169:15-20.
[19] Steptoe A,Hamer M,Chida Y.The effects of acute psychological stress on circulating inflammatory factors in humans:A review and meta-analysis[J].Brain Behavior and Immunity,2007,21(7):901-912.
[20] Kronfol Z,Remick DG.Cytokines and the brain:Implications for clinical psychiatry[J].Am J Psychiatry,2000,157(5):683-694.
[21] Simon NM,McNamara K,Chow CW,et al.A detailed examination of cytokine abnormalities in Major Depressive Disorder[J].Eur Neuropsychopharmacol,2008,18(3):230-233.
[22] Sheu BC,Chang WC,Cheng CY,et al.Cytokine regulation networks in the cancer microenvironment[J].Frontiers in Bioscience,2008,13:6255.
[23] Elenkov IJ,Wilder RL,Chrousos GP,et al.The sympathetic nerve-An integrative interface between two supersystems:The brain and the immune system[J].Pharmacological Reviews,2000,52(4):595-638.
[24] Santos JC,Pyter LM.Neuroimmunology of behavioral comorbidities associated with cancer and cancer treatments[J].Frontiers in Immunology,2018,9:17.
[25] Leonard BE,Myint A.The psychoneuroimmunology of depression[J].Human Psychopharmacol-Clin Exp,2009,24(3):165-175.
[26] Hou R,Baldwin DS.A neuroimmunological perspective on anxiety disorders[J].Hum Psychopharmacol,2012,27(1):6-14.
[27] Arranz L,Guayerbas N,De la Fuente M.Impairment of several immune functions in anxious women[J].J Psychosomatic Res,2007,62(1):1-8.
[28] Lutgendorf SK,Lamkin DM,DeGeest K,et al.Depressed and anxious mood and T-cell cytokine expressing populations in ovarian cancer patients[J].Brain Behav Immun,2008,22(6):890-900.
[29] Takkouche B,Regueira C,Gestal-Otero JJ.A cohort study of stress and the common cold[J].Epidemiology,2001,12(3):345-349.
[30] Huang YQ,Wang ZF,Zhou WP,et al.The changes and clinical significance of IL-6,TNF-α and CRP levels in patients with colorectal cancer[J].Oncolory Progress,2018,16(9):1140-1142.[黄有群,王振奋,周卫平.结直肠癌患者 IL-6、TNF-α、CRP 的水平变化特点及临床意义[J].癌症进展,2018,16(9):1140-1142.]
[31] Yang Y,Tian M.Relationship between TNF-α,IL-6 and IL-8 levels and clinical stage in patients with colorectal cancer[J].Labeled Immunoassays and Clin Med,2016,23(7):790-793.[杨勇,田敏.结直肠癌患者TNF-α、IL-6、IL-8水平与临床分期的关系与研究[J].标记免疫分析与临床,2016,23(7):790-793.]