Correlation between expression of serum AGR2, PGK1, MRP8/14 and postoperative efficacy evaluation and survival in patients with prostate cancer
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摘要: 目的:探讨血清前梯度蛋白2(AGR2)、磷酸甘油酸激酶1(PGK-1)、髓样相关蛋白8/14(MRP8/14)表达情况与前列腺癌(PCa)患者术后疗效评估及生存情况的相关性。方法:选取2016年1月至2017年1月收治的83例PCa患者为PCa组,另选取64例良性前列腺增生(BPH)患者为BPH组,50例健康男性为对照组,测定所有研究对象血清AGR2、PGK1、MRP8/14水平,分析其与PCa患者术后疗效及生存情况相关性。结果:PCa组血清AGR2、PGK1、MRP8/14水平明显高于BPH组、对照组(P＜0.05);PCa患者血清AGR2水平与前列腺特异性抗原(PSA)水平、分化程度、淋巴结转移、骨转移、TNM分期有关,血清PGK1水平与PSA水平、淋巴结转移、侵袭、骨转移、TNM分期有关,血清MRP8/14水平与PSA水平、淋巴结转移、骨转移、TNM分期有关(P＜0.05);PCa组术后血清AGR2、PGK1、MRP8/14水平明显降低(P＜0.05);随访9~35个月,平均(22.48±4.27)个月,Kaplan-Meier生存曲线显示,高血清AGR2、PGK1、MRP8/14水平组总生存率明显低于低血清AGR2、PGK1、MRP8/14水平组(P＜0.05);多因素Cox回归分析显示,PSA (HR=0.356,95%CI=0.372~0.953)、骨转移(HR=1.642,95%CI=1.025~2.615)、AGR2(HR=3.441,5%CI=0.085~23.154)、PGK1(HR=4.386,5%CI=0.924~20.536)、MRP8/14(HR=2.758,95%CI=1.035~20.625)为PCa患者预后风险因素(P＜0.05);ROC曲线显示,血清AGR2+PGK1+MRP8/14水平(AUC=0.911,95%CI=0.850~0.954)诊断PCa的敏感度、特异度、准确度高于AGR2(AUC=0.783,95%CI=0.704~0.850)、PGK1(AUC=0.794,95%CI=0.716~0.859)、MRP8/14(AUC=0.770,95%CI=0.689~0.838)单独诊断。结论:血清AGR-2、PGK1、MRP8/14水平变化与PCa患者术后疗效和生存情况密切相关,联合检测进而提升PCa诊断价值。
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关键词:
- 前列腺癌 /
- 前梯度蛋白2 /
- 磷酸甘油酸激酶1 /
- 髓样相关蛋白8/14
Abstract: Objective: To investigate the relationship between the expression of anterior gradient 2(AGR2), phosphoglycerate kinase 1(PGK-1), myeloid-related protein 8/14(MRP8/14) and postoperative curative effect and survival assessment in patients with prostate cancer(PCa).Methods: A total of 83 PCa patients admitted to our hospital(January 2016 to January 2017) were selected as the PCa group, another 64 patients with benign prostatic hyperplasia(BPH) were selected as the BPH group, and 50 healthy men were selected as the control group. The serum AGR2, PGK1, and MRP8/14 levels of all subjects were analyzed and their correlation with postoperative efficacy and survival of PCa patients was analyzed.Results: The serum AGR2, PGK1, and MRP8/14 levels in the PCa group were significantly higher than those in the BPH group and the control group(P＜0.05). The serum AGR2 level in PCa patients was related to PSA levels, degree of differentiation, lymph node metastasis, bone metastasis, and TNM staging. Serum PGK1 level was related to PSA level, lymph node metastasis, invasion, bone metastasis, and TNM staging. Serum MRP8/14 level was related to PSA level, lymph node metastasis, bone metastasis and TNM staging(P＜0.05). Postoperative serum AGR2, PGK1 and MRP8/14 levels in the PCa group significantly decreased(P＜0.05). All patients received follow-up for 9 to 35 months with an average of(22.48±4.27) months. Kaplan-Meier survival curve showed that the overall survival rate of the group with high serum AGR2, PGK1 and MRP8/14 levels was significantly lower than that with low serum AGR2, PGK1 and MRP8/14 levels Group(P＜0.05). Multivariate Cox regression analysis showed that PSA(HR=0.356, 95%CI=0.372-0.953), bone metastasis(HR=1.642, 95%CI=1.025-2.615), AGR2(HR=3.441, 95%CI=0.085-23.154), PGK1(HR=4.386, 95%CI=0.924-20.536) and MRP8/14(HR=2.758, 95%CI=1.035-20.625) were prognostic risk factors for PCa patients(P＜0.05). ROC curve showed that the serum AGR2+PGK1+MRP-8/14 level(AUC=0.911, 95%CI=0.850-0.954) was more sensitive, specific, and accurate in diagnosing PCa than AGR2(AUC=0.783, 95%CI=0.704-0.850), PGK1(AUC=0.794, 95%CI=0.716-0.859), MRP8/14(AUC=0.770, 95%CI=0.689-0.838) separately.Conclusion: The changes of serum AGR2, PGK1, and MRP8/14 levels might be closely related to the postoperative efficacy and survival of PCa patients. Combined detection could enhance the diagnostic value of PCa. -
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[1] 顾成元,秦晓健,黄永墙,等.我国部分省市前列腺癌精准筛查初步结果分析[J].中华医学杂志,2019,99(42):3292-3297.
[2] 汪鑫,蔡凯,王梁,等.前列腺癌骨转移的预测因素分析[J].中国医科大学学报,2018,47(11):1025-1028.
[3] 魏筠妮,张春玉,傅松滨.分泌蛋白AGR2在肿瘤中的研究进展[J].国际遗传学杂志,2019,41(2):130-135.
[4] 林莉,江庆萍,林丹,等.子宫内膜癌组织中PGK1的表达及其与预后的关系[J].南方医科大学学报,2018,38(4):471-476.
[5] 李影,刘红宁,邓晓霞,等.恶性肿瘤有氧糖酵解关键酶研究进展[J].江西中医药,2019,50(1):73-77.
[6] SumováB,Cerezo LA,SzczukováL,et al.Circulating S100 proteins effectively discriminate SLE patients from healthy controls:a cross-sectional study[J].Rheumatol Int,2019,39(3):469-478.
[7] Edge SB,Compton CC.The American Joint Committee on Cancer:the 7th edition of the AJCC cancer staging manual and the future of TNM[J].Ann Surg Oncol,2010,17(6):1471-1474.
[8] 中华医学会泌尿外科分会.前列腺癌诊断治疗指南[J].继续医学教育,2007,21(6):30-39.
[9] Zhu Q,Mangukiya HB,Mashausi DS,et al.Anterior gradient 2is induced in cutaneous wound and promotes wound healing through its adhesion domain[J].FEBS J,2017,284(17):2856-2869.
[10] Lan J,Wu X,Luo L,et al.Fluorescent Ag clusters conjugated with anterior gradient-2antigen aptamer for specific detection of cancer cells[J].Talanta,2019,197:86-91.
[11] Fritzsche FR,Dahl E,Dankof A,et al.Expression of AGR2in non small cell lung cancer[J].Histol Histopathol,2007,22(7):703-8.
[12] Negi H,Merugu SB,Mangukiya HB,et al.Anterior Gradient-2 monoclonal antibody inhibits lung cancer growth and metastasis by upregulating p53pathway and without exerting any toxicological effects:A preclinical study[J].Cancer Lett,2019,449:125-134.
[13] Zhang P,Xie Y,Li Z,et al.Relationship of serum anterior gradient 2level with clinicopathologic features and prognosis of patients with prostate cancer[J].Cancer Res,2017,29(9):598-601.
[14] 徐小虎,丁玉芹,邰兆琴,等.MRI联合PSA在前列腺癌诊断和治疗效果评估中的应用[J].实用癌症杂志,2018,33(12):2062-2064.
[15] Guo H,Zhu Q,Yu X,et al.Tumor-secreted anterior gradient-2binds to VEGF and FGF2and enhances their activities by promoting their homodimerization[J].Oncogene,2017,36(36):5098-5109.
[16] Maurel M,Obacz J,Avril T,et al.Control of anterior GRadient 2(AGR2)dimerization links endoplasmic reticulum proteostasis to inflammation[J].EMBOMol Med,2019,11(6):e10120.
[17] Fu Q,Yu Z.Phosphoglycerate kinase 1(PGK1)in cancer:A promising target for diagnosis and therapy[J].Life Sci,2020,256:117863.
[18] Fiorillo A,Petrosino M,Ilari A,et al.The phosphoglycerate kinase 1variants found in carcinoma cells display different catalytic activity and conformational stability compared to the native enzyme[J].PLoSOne,2018,13(7):e0199191.
[19] 张岚,王英聪,谢晓莺,等.磷酸甘油酸激酶1对肝癌细胞侵袭转移及肝癌预后的影响[J].中华肝脏病杂志,2017,25(6):446-451.
[20] Jin C,Zhu X,Wu H,et al.Perturbation of phosphoglycerate kinase 1(PGK1)only marginally affects glycolysis in cancer cells[J].J Biol Chem,2020,295(19):6425-6446.
[21] 束方鹏.磷酸甘油酸变位酶1在前列腺癌进展中的功能及通过外泌体促进肿瘤细胞迁移的机制研究[D].广东:南方医科大学,2018.
[22] Shao F,Yang X,Wang W,et al.Associations of PGK1promoter hypomethylation and PGK1-mediated PDHK1phosphorylation with cancer stage and prognosis:a TCGA pan-cancer analysis[J].Cancer Commun(Lond),2019;39(1):54.
[23] Diklic'M,Mitrovic'-Ajtic'O,Suboticki T,et al.IL6inhibition of inflammatory S100A8/9proteins is NF-κBmediated in essential thrombocythemia[J].Cell Biochem Funct,2020,38(4):362-372.
[24] Kovacic'M,Mitrovic'-Ajtic'O,Beleslin-Cokic'B,et al.TLR4and RAGE conversely mediate pro-inflammatory S100A8/9-mediated inhibition of proliferationlinked signaling in myeloprolifer-ative neoplasms[J].Cell Oncol(Dordr),2018,41(5):541-553.
[25] Li S,Xu F,Wang L,et al.Abstract 4723:Improving prognosis or promoting progression?Double sword of S100A8in colorectal cancer[J].Cancer Research,2017,77(13Supplement):4723-4723.
[26] Podgórska M,Oldak M,Marthaler A,et al.Chronic Inflammatory Microenvironment in Epidermodysplasia Verruciformis Skin Lesions:Role of the Synergism Between HPV8E2and C/EBPβto Induce Pro-Inflammatory S100A8/A9 Proteins[J].Front Microbiol,2018,9:392.
[27] Minner S,Hager D,Steurer S,et al.Down-Regulation of S100A8is an Independent Predictor of PSA Recurrence in Prostate Cancer Treated by Radical Prostatectomy[J].Neoplasia,2019,21(9):872-881.
[28] Podgórska M,Oldak M,Marthaler A,et al.Chronic Inflammatory Microenvironment in Epidermodysplasia Verruciformis Skin Lesions:Role of the Synergism Between HPV8E2and C/EBPβto Induce Pro-Inflammatory S100A8/A9 Proteins[J].Front Microbiol,2018,9:392.
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