BCAT1作为胰腺导管腺癌潜在诊断标志物的临床应用价值研究

The clinical application value of BCAT1 as a potential diagnostic biomarker for pancreatic ductal adenocarcinoma

目的 本研究拟验证前期研究发现的bcat1基因表达产物支链氨基酸转氨酶1(BCAT1)作为胰腺导管腺癌潜在血清学诊断标志物的临床应用价值。方法 收集临床PDAC患者血清样本作为实验组,收集胃癌、肝癌、结直肠癌、慢性胰腺炎患者及健康人群血清样本作为对照,采用酶联免疫吸附实验(ELISA)检测血清样本BCAT1浓度,验证其作为标志物的临床诊断价值。结果 ELISA结果显示PDAC组患者血清BCAT1浓度显著高于健康对照组,差异有统计学意义(P<0.05,U=1 206)。PDAC组患者血清BCAT1浓度高于慢性胰腺炎组,差异有统计学意义(P<0.05,H=33.80);与其他消化道肿瘤相比,高于肝癌组和结直肠癌组,差异有统计学意义(P<0.05,H=33.80),与胃癌组差异无统计学意义(P>0.05,H=33.80)。BCAT1与CA19-9的相关性较好,且差异有统计学意义(P<0.05,R^(2)=0.080 52),与CEA(R^(2)=2.265e-005)、CA125(R^(2)=0.025 88)和CA72-4(R^(2)=0.007 7)相关性较低,差异无统计学意义(P>0.05);BCAT1诊断PDAC的AUC优于CA72-4,与CA125和CEA相当,劣于CA19-9;BCAT1 cut off值为1.556ng/mL,敏感度为64.1%,特异度为80%。BCAT1在PDAC早中期患者血清浓度中位数为0.283 ng/mL,晚期患者升高为0.482 ng/mL,差异有统计学意义(P<0.05,U=1029);在肿瘤≥40 mm(U=641)、中低分化(U=435)、胰头部位(H=2.767)均表现为表达水平升高,差异无统计学意义(P均>0.05)。动态观测的BCAT1浓度在第0天和1~30天(U=44)、31~60天和61~90天(U=36)浓度差异有统计学意义(P均<0.05)。结论 BCAT1作为潜在的血清学标志物,对于PDAC的鉴别诊断、肿瘤分期、疾病进展判断具有参考价值,是目前现有的PDAC血清标志物的有益补充。

Objective To verify the clinical application value of BCAT1,the expression product of the bcat1 gene,as a potential serum diagnostic biomarker for pancreatic ductal adenocarcinoma(PDAC).Method Serum samples were collected from PDAC patients as the experimental group,and from patients with gastric cancer,liver cancer,colorectal cancer,chronic pancreatitis,and healthy individuals as the con⁃trol group.Enzyme⁃linked immunosorbent assay(ELISA)was used to detect the concentration of BCAT1 in the serum samples to verify its clinical diagnostic value as a biomarker.Results ELISA results indicated that the serum BCAT1 concentration in patients with PDAC was significantly higher than that in the healthy control group,with a statistically significant difference(P<0.05,U=1206).The serum BCAT1 concentration in the PDAC group was higher than in the chronic pancreatitis group,with a statistically significant difference(P<0.05,H=33.80).Compared to other gastrointestinal tumors,it was higher than in the liver cancer group and colorectal cancer group,with a statistically significant difference(P<0.05,H=33.80),but there was no statis⁃tically significant difference compared to the gastric cancer group(P>0.05,H=33.80).BCAT1 had a relative⁃ly good correlation with CA19⁃9,with a statistically significant difference(P<0.05,R^(2)=0.08052),and lower correlations with CEA(R^(2)=2.265e⁃005),CA125(R^(2)=0.02588),and CA72⁃4(R^(2)=0.0077),without statisti⁃cally significant differences(P>0.05).The diagnostic AUC of BCAT1 for PDAC was better than that of CA72⁃4,comparable to CA125 and CEA,but inferior to CA19⁃9.The BCAT1 cut⁃off value was 1.556 ng/mL,with a sensitivity of 64.1%and a specificity of 80%.The median serum concentration of BCAT1 in early to mid⁃stage PDAC patients was 0.283 ng/mL,which increased to 0.482 ng/mL in late⁃stage patients,with a statistically significant difference(P<0.05,U=1029).In tumors≥40 mm(U=641),moderate to poor differentiation(U=435),and pancreatic head location(H=2.767),the expression level was increased,but the difference was not statistically significant(both P>0.05).Dynamic observations of BCAT1 concentration showed statisti⁃cally significant differences between day 0 and days 1 to 30(U=44),as well as between days 31 to 60 and days 61 to 90(U=36),with the differences being statistically significant(both P<0.05).Conclusion BCAT1,as a potential serum biomarker,holds reference value for the differential diagnosis of PDAC,tumor staging,and disease progression assessment.It is a valuable addition to the current PDAC serum biomarkers.