Shah Chintan, Hong Young-Rock, Bishnoi Rohit, Ali Azka, Skelton William Paul, Dang Long H, Huo Jinhai, Dang Nam H
Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL, United States.
Department of Health Services Research, Management and Policy, College of Public Health and Health Professions, University of Florida, Gainesville, FL, United States.
Front Oncol. 2020 Mar 31;10:405. doi: 10.3389/fonc.2020.00405. eCollection 2020.
Dipeptidyl peptidase-4 (DPP4), a cell surface protein, exhibits a crucial role in tumor biology and regulation of the immune system. We aim to study the impact of DPP4 inhibitors (DPP4i) in patients with prostate cancer (PRC), pancreatic cancer (PC) and breast cancer (BC). Using the SEER and Medicare linked database, we identified patients with PRC or PC or BC with coexisting type II diabetes mellitus between 2007 and 2015. Patients were classified into four groups: (1) not on either DPP4i or metformin (reference group), this group included patient that were on anti-diabetic agents other than metformin or DPP4i (2) metformin only, (3) DPP4i only, and (4) DPP4i along with metformin (combination group). Overall survival (OS) analyses were performed using SAS®, version 9.4. We identified 15,330 patients with PRC, 5,359 patients with PC and 16,085 patients with BC. In PRC cohort, patients on DPP4i had significant survival advantage with HR 0.77 (95% CI: 0.64-0.93), = 0.005 when compared to the reference group. Patients taking metformin also had significant OS benefit with HR 0.87 (95% CI: 0.81-0.93), < 0.0001 when compared to the reference group. However, in BC cohort, OS did not favor the patients taking DPP4i with HR 1.07 (95% CI: 0.93-1.25, = 0.33). Similarly, in PC cohort, OS was indifferent for the patients on DPP4i with HR 1.07 (95% CI: 0.93-1.24, = 0.68). Upon subgroup analyses of PRC patients, the survival favored the group taking DPP4i, irrespective of stage, use of chemotherapy, androgen-deprivation therapy, and prostatectomy or radiation therapy. DPP4i seems to improve survival in PRC patients; however, not in PC or BC patients. While the exact mechanism involved remains to be elucidated, a prospective clinical trial would help to confirm these findings.
二肽基肽酶4(DPP4)是一种细胞表面蛋白,在肿瘤生物学和免疫系统调节中发挥着关键作用。我们旨在研究DPP4抑制剂(DPP4i)对前列腺癌(PRC)、胰腺癌(PC)和乳腺癌(BC)患者的影响。利用SEER和医疗保险关联数据库,我们确定了2007年至2015年间患有PRC或PC或BC且并存II型糖尿病的患者。患者被分为四组:(1)未使用DPP4i或二甲双胍(参照组),该组包括使用除二甲双胍或DPP4i以外的抗糖尿病药物的患者;(2)仅使用二甲双胍;(3)仅使用DPP4i;(4)DPP4i与二甲双胍联用(联合组)。使用SAS®9.4版进行总生存期(OS)分析。我们确定了15330例PRC患者、5359例PC患者和16085例BC患者。在PRC队列中,与参照组相比,使用DPP4i的患者具有显著的生存优势,风险比(HR)为0.77(95%置信区间:0.64 - 0.93),P = 0.005。服用二甲双胍的患者也有显著的OS获益,HR为0.87(95%置信区间:0.81 - 0.93),与参照组相比P < 0.0001。然而,在BC队列中,使用DPP4i的患者的OS并无优势,HR为1.07(95%置信区间:0.93 - 1.25,P = 0.33)。同样,在PC队列中,使用DPP4i的患者的OS无差异,HR为1.07(95%置信区间:0.93 - 1.24,P = 0.68)。对PRC患者进行亚组分析时,无论分期、化疗使用情况、雄激素剥夺治疗以及前列腺切除术或放射治疗如何,生存情况都有利于使用DPP4i的组。DPP4i似乎能改善PRC患者的生存;然而,对PC或BC患者则不然。虽然具体机制仍有待阐明,但一项前瞻性临床试验将有助于证实这些发现。