Relationship between serum bone morphogenetic protein level and prognosis of non-small cell lung cancer
LIU Qiwei1 WU Qiong2 WANG Zhiwu2
1.Nuclear Medicine Laboratory, Tangshan People’s Hospital, Hebei Province, Tangshan 063000, China;
2.the First Department of Oncology, Tangshan People’s Hospital, Hebei Province, Tangshan 063000, China
Abstract:Objective To evaluate the effect of serum bone morphogenetic protein-2 (BMP-2) level on the prognosis of patients with non-small cell lung cancer (NSCLC). Methods A total of 57 NSCLC patients admitted to Tangshan People’s Hospital, Hebei Province from January to December 2017 were selected. Clinicopathological features and overall survival data of the patients were collected and the serum BMP-2 level of the patients were detected. The relationship between serum BMP-2 level and clinicopathological characteristics and the relationship between serum BMP-2 level and prognosis in patients with lung cancer were analyzed, and the influence of BMP-2 level and other clinicopathological factors on patients with NSCLC was discussed by univariate and multivariate survival analysis. Results The difference of serum BMP-2 level in patients with different pathological stages and metastatic sites was statistically significant (P < 0.05). There was no significant difference in serum BMP-2 level among patients with different age, sex, histological type and degree of tumor cell differentiation (P > 0.05). The median survival time of all patients was 9.8 months (95%CI: 7.3-11.5). The median survival time of NSCLC patients with high BMP-2 level was 6.8 months (95%CI: 4.5- 9.3), shorter than that of NSCLC patients with low BMP-2 level was 12.1 months (95%CI: 9.4-14.8), the difference was highly statistically significant (χ2 = 9.15, P < 0.001). Single factor survival analysis found that the pathological stage Ⅳ (HR = 1.539, 95%CI: 1.127-3.228, P = 0.013), number of metastatic sites (≥three sites) (HR = 1.738, 95%CI: 1.194-4.380, P = 0.001) and BMP-2 levels (≥75 pg/mL) (HR = 2.019, 95%CI: 1.233-6.229, P = 0.000) were the adverse factors affecting the prognosis of patients with NSCLC. Multivariate survival analysis showed that serum BMP-2 level (≥75 pg/mL) (HR = 1.837, 95%CI: 1.146-3.473, P = 0.007) and number of metastatic sites (≥three sites) (HR = 1.199, 95%CI: 1.028-2.337, P = 0.037) were independent adverse factors affecting the prognosis of NSCLC patients. Conclusion High serum BMP-2 level and more than three metastatic sites are independent adverse prognostic factors for NSCLC patients, which can predict the prognosis of NSCLC.
刘启为1 吴琼2 王志武2. 血清骨形态发生蛋白水平与非小细胞肺癌预后的关系[J]. 中国医药导报, 2020, 17(35): 42-45.
LIU Qiwei1 WU Qiong2 WANG Zhiwu2. Relationship between serum bone morphogenetic protein level and prognosis of non-small cell lung cancer. 中国医药导报, 2020, 17(35): 42-45.
[1] Loozen LD,Vandersteen A,Kragten AH,et al. Bone formation by heterodimers through non-viral gene delivery of BMP-2/6 and BMP-2/7 [J]. Eur Cell Mater,2018,35:195-208.
[2] Wozney JM,Rosen V,Celeste AJ,et al. Novel regulators of bone formation:molecular clones and activities [J]. Science,1988,242(4885):1528-1534.
[3] Kaito T,Morimoto T,Mori Y,et al. BMP-2/7 heterodimer strongly induces bone regeneration in the absence of increased soft tissue inflammation [J]. Spine J,2018,18(1):139-146.
[4] Hogan BL. Bone morphogenetic proteins:multifunctional regulators of vertebrate development [J]. Genes Dev,1996, 10(13):1580-1594.
[5] Wu YT,Chang HM,Huang HF,et al. Bone morphogenetic protein 2 regulates cell-cell communication by down-regulating connexin43 expression in luteinized human granulosa cells [J]. Mol Hum Reprod,2017,23(3):155-165.
[6] Cao X,Chen D. The BMP signaling and in vivo bone formation [J]. Gene,2005,357(1):1-8.
[7] Futrega K,Mosaad E,Chambers K,et al. Bone marrow-derived stem/stromal cells(BMSC)3D microtissues cultured in BMP-2 supplemented osteogenic induction medium are prone to adipogenesis [J]. Cell Tissue Res,2018, 374(3):541-553.
[8] Deng H,Makizumi R,Ravikumar TS,et al. Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells [J]. Exp Cell Res,2007,313(5):1033-1044.
[9] Zhao H,Ayrault O,Zindy F,et al. Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development [J]. Genes Dev,2008,22(6):722-727.
[10] Yang J,Xu T,Gomez DR,et al. Nomograms incorporating genetic variants in BMP/Smad4/Hamp pathway to predict disease outcomes after definitive radiotherapy for non-small cell lung cancer [J]. Cancer Med,2018,7(6):2247-2255.
[11] Park Y,Kang MH,Seo HY,et al. Bone morphogenetic protein-2 levels are elevated in the patients with gastric cancer and correlate with disease progression [J]. Med Oncol,2010,27(4):1192-1199.
[12] Travis WD,Brambilla E,Nicholson AG,et al. The 2015 World Health Organization Classification of Lung Tumors:Impact of Genetic,Clinical and Radiologic Advances Since the 2004 Classification [J]. J Thorac Oncol,2015,10(9):1243-1260.
[13] Lim W,Ridge CA,Nicholson AG,et al. The 8th lung cancer TNM classification and clinical staging system:review of the changes and clinical implications [J]. Quant Imaging Med Surg,2018,8(7):709-718.
[14] Scimeca M,Giocondo R,Montanaro M,et al. BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin [J]. Cells,2020,9(6):1381.
[15] Wang S,Gu M,Jiang H,et al. BMP-2 upregulates the AKT/mTOR pathway in breast cancer with microcalcification and indicates a poor prognosis [J]. Clin Transl Oncol,2020,22(8):1263-1271.
[16] Chen X,Zhang Y. BMP-2 and miR-29c in osteosarcoma tissues on proliferation and invasion of osteosarcoma cells [J]. Oncol Lett,2019,17(6):5389-5394.
[17] 胡小平,鲁艳,李新军,等.BMP-2通过BMP/Smad/ID3通路调控非小细胞肺癌A549细胞的凋亡[J].肿瘤药学,2020,10(2):176-180.
[18] 王福琴.BMP-2对肺癌细胞上皮-间质转化的影响及其作用机制[J].生物化工,2019,5(1):77-80.
[19] 赵淦琳炜,杨毅.p38MAPK信号通路参与BMP2诱导MSCs的归巢效应研究[J].中国临床研究,2020,33(4):437-441.
[20] 费正华,杨晓蕾,陈云亮,等.血清BMP-2蛋白在预测进展期非小细胞肺癌疗效及预后中的作用[J].浙江医学,2014,36(23):1903-1906.