Abstract:Objective: To explore the diagnostic value of combined detection of serum Src homology domain 2 protein B1 (SH2B1), Nedd4 family interacting protein 1 (NDFP1), and α-hydroxybutyrate dehydrogenase (α-HBDH) in differentiating benign and malignant solitary pulmonary nodules (SPN). Methods: Totally 260 SPN patients in our hospital were designated as the SPN group, and were classified into a benign group (112 cases) and a malignant group (148 cases) based on pathological examination results. Meanwhile, 200 healthy individuals were made the control group. The ELISA method was used to detect serum SH2B1, NDFIP1, and α-HBDH. Multivariate logistic regression was used to explore the risk factors affecting SPN malignancy. Relative risk analysis of serum SH2B1, NDFIP1, and α-HBDH levels on malignant transformation of SPN. ROC curve was plotted to evaluate the differential diagnostic value of serum SH2B1, NDFIP1, and α-HBDH for benign and malignant SPN. Results: Compared with the control group, the SPN group had higher serum SH2B1 and α-HBDH (t=46.344, 28.857, P<0.05), and lower NDFIP1 (t=26.385, P<0.05). The malignant group had higher serum SH2B1 and α-HBDH than the benign group (t=6.877, 6.705, P<0.05), and lower NDFIP1 than the benign group (t=6.959, P<0.05). Multivariate logistic regression analysis revealed that spiny nodule morphology (OR=3.613, 95%CI: 1.182~7.203), solid nodules (OR=4.079, 95%CI: 1.410~11.801), elevated SH2B1 levels (OR=2.440, 95%CI: 1.290~4.614), and high α-HBDH expression (OR=2.228, 95%CI: 1.346~3.687) were independent risk factors for SPN malignancy, whereas high NDFIP1 expression (OR=0.724, 95%CI: 0.559~0.938) was a protective factor (P<0.05). Relative risk analysis further indicates that patients with high levels of SH2B1 and high levels of α-HBDH have a 2.498-fold and 2.424-fold increased risk of developing malignant SPN, respectively, compared to those with low levels; whereas patients with high levels of NDFIP1 had a risk that was 0.492 times lower than that of patients with low levels. The AUC for the combined diagnosis of malignant SPN using serum SH2B1, NDFIP1, and α-HBDH was 0.919, which was superior to the combined diagnosis using nodule morphology and nodule characteristics (Zcombined-nodule morphology + nodule characteristics=4.611, P<0.001). Conclusion: The changes in serum SH2B1, NDFIP1, and α-HBDH are closely related to the benign and malignant natures of SPN. All three have certain differential diagnostic value for benign and malignant SPN, and combined detection has high differential diagnostic efficacy.
[1] Xie X,Liu K,Luo K,et al.Value of dual-layer spectral detector computed tomography in the diagnosis of benign/malignant solid solitary pulmonary nodules and establishment of a prediction model[J].Front Oncol,2023,13(1):1147479. [2] 赵亚波,董鑫,郭彦璞,等.基于高分辨率CT显示孤立性肺结节与肺动静脉关系在鉴别结节良恶性中的价值研究[J].实用医学影像杂志,2023,24(3):177-180. [3] Zhang L,Xu X,Pan Y,et al.High expression of SH2B adaptor protein 1 (SH2B1) indicates poor prognosis in colorectal cancer[J].Neoplasma,2021,68(3):490-497. [4] Cheng Y,Lu X,Li F,et al.NDFIP1 limits cellular TAZ accumulation via exosomal sorting to inhibit NSCLC proliferation[J].Protein Cell,2023,14(2):123-136. [5] 钟临锋,袁飞,陈兴,等.多层螺旋CT联合血清ChE α-HBDH PGRN对肺结核合并肺癌的诊断价值[J].河北医学,2024,30(10):1644-1648. [6] 中华医学会呼吸病学分会肺癌学组,中国肺癌防治联盟专家组.肺部结节诊治中国专家共识[J].中华结核和呼吸杂志,2015,38(4):249-254. [7] 刘岩,韩风伟,闫丽娜,等.SH2B1通过活化PI3K/Akt通路促进胶质瘤细胞增殖[J].中国免疫学杂志,2021,37(7):834-838. [8] Liu J,Zhu J,Xiao Z,et al.BBOX1-AS1 contributes to colorectal cancer progression by sponging hsa-miR-361-3p and targeting SH2B1[J].FEBS Open Bio,2022,12(5):983-992. [9] Torrino S,Tiroille V,Dolfi B,et al.UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling[J].Elife,2021,10(1):e68348. [10] Liu Y,Hu Q,Wang X.AFAP1-AS1 induces cisplatin resistance in non-small cell lung cancer through PI3K/AKT pathway[J].Oncol Lett,2020,19(1):1024-1030. [11] Li Y,Cheng Q,Gao J,et al.WWP1 upregulation predicts poor prognosis and promotes tumor progression by regulating ubiquitination of NDFIP1 in intrahepatic cholangiocarcinoma[J].Cell Death Discov,2022,8(1):107-119. [12] El Sayed S M.Biochemical origin of the warburg effect in light of 15 years of research experience: a novel evidence-based view (an expert opinion article)[J].Onco Targets Ther,2023,16(1):143-155. [13] Yuan Z M,Wang L H,Chen C.Prognostic value of serum α-HBDH levels in patients with lung cancer[J].World Surg Oncol,2023,21(1):78-85.