Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Carcinogenesis. 2022 Sep 19;43(8):736-745. doi: 10.1093/carcin/bgac052.
To improve the early detection of gastric cancer (GC), there is a growing need for novel and efficient biomarkers. We aimed to evaluate diagnostic value of thioredoxin reductase 1 (TXNRD1), which was found to be over expressed in various malignancies. We found that TXNRD1 has a higher expression level in GC tissues compared with adjacent normal tissues, and high TXNRD1 expression was significantly associated with poor outcomes of GC patients. Next, a total of 1446 cases were collected, with 896 cases in GC, 322 in benign gastric disease and 228 in healthy controls. We noticed plasma thioredoxin reductase (TrxR) level in GC [8.4 (7.1, 9.7) U/ml] was significantly higher than that in benign disease [6.1 (5.4, 7.2) U/ml] or healthy controls [3.7 (1.7, 5.6) U/ml]. Receiver operating characteristic analysis showed that the optimal cutoff value of TrxR activity for GC diagnosis was set at 5.75 U/ml with an area under the curve of 0.945. Moreover, a combined panel of TrxR and routine tumor markers could further elevate the diagnostic efficacy compared to a single biomarker. Finally, by measuring pre- and post-treatment TrxR activity and routine tumor markers, we found the change trend of them was broadly consistent, and plasma TrxR activity was significantly decreased in patients treated with platinum/fluorouracil-based therapy. Our findings recommend plasma TrxR activity combined with tumor markers as effective diagnostic tools for GC patients. As well, plasma TrxR has the potential to monitor therapeutic efficacy.
为了提高胃癌（GC）的早期检测水平，人们越来越需要新的、有效的生物标志物。我们旨在评估硫氧还蛋白还原酶 1（TXNRD1）的诊断价值，该酶在各种恶性肿瘤中表达过高。我们发现 TXNRD1 在 GC 组织中的表达水平高于相邻正常组织，高 TXNRD1 表达与 GC 患者的不良预后显著相关。接下来，我们共收集了 1446 例病例，其中 896 例为 GC，322 例为良性胃部疾病，228 例为健康对照。我们注意到 GC 患者的血浆硫氧还蛋白还原酶（TrxR）水平[8.4（7.1，9.7）U/ml]明显高于良性疾病[6.1（5.4，7.2）U/ml]或健康对照[3.7（1.7，5.6）U/ml]。受试者工作特征分析显示，TrxR 活性诊断 GC 的最佳截断值为 5.75 U/ml，曲线下面积为 0.945。此外，与单一生物标志物相比，TrxR 和常规肿瘤标志物的联合检测可进一步提高诊断效能。最后，通过测量治疗前后的 TrxR 活性和常规肿瘤标志物，我们发现它们的变化趋势大致一致，且接受铂类/氟尿嘧啶为基础的治疗的患者血浆 TrxR 活性明显降低。我们的研究结果表明，血浆 TrxR 活性联合肿瘤标志物可作为 GC 患者有效的诊断工具。此外，血浆 TrxR 具有监测治疗效果的潜力。
