Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin, 300060, P.R. China.
BMC Cancer. 2022 Oct 8;22(1):1052. doi: 10.1186/s12885-022-10142-0.
Cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer which is the major cause of death in women worldwide. Although squamous cell carcinoma antigen (SCC-Ag) is widely used to detect CESC, it is not sensitive and specific enough to predict the disease.
We investigated serum CXC motif chemokine 10 (CXCL10) as potential diagnostic biomarker in detecting CESC in this study. Serum levels of CXCL10 and SCC-Ag were measured by ELISA or automated immunoassay in 345 participants, including 189 patients with different stages of CESC, 75 patients with cervical intraepithelial neoplasia, and 81 healthy individuals. Performances of CXCL10 and SCC-Ag as single biomarkers were analyzed by the ROC curves. The changes of serum levels of CXCL10 and SCC-Ag in 10 longitudinal followed-up CESC patients with partial response (PR) during chemoradiotherapy or chemotherapy were evaluated.
The two markers showed similar diagnostic capacity in distinguishing both CESC early stage from healthy controls (AUCCXCL10 = 0.740, AUCSCC-Ag = 0.710) and all CESC from healthy controls (AUCCXCL10 = 0.775, AUCSCC-Ag =0.793). Moreover, CXCL10 showed ability in distinguishing cervical intraepithelial neoplasia from healthy control (AUCCXCL10 = 0.727) and cervical cancer SCC-Ag-negative from healthy control. (AUCCXCL10 = 0.739). The combination of CXCL10 and SCC-Ag displayed significant improvement of AUCs than individual SCC-Ag or CXCL10 in the analysis groups (healthy vs all cervical cancer, healthy vs cervical cancer early stage). The AUCs were improved to 0.877 (AUCSCC-Ag = 0.793, P < 0.05) to distinguish healthy controls from all CESC and 0.828(AUCSCC-Ag = 0.710, P < 0.05) to distinguish healthy controls from CESC early stage by the combination of the two markers, respectively. Significant differences of serum CXCL10 levels were found between CESC patients at late tumor stage and CESC patients at early tumor stage (P < 0.01). Serum CXCL10 levels of the CESC patients who had partial response after treatment significantly decreased during treatment (P = 0.013), whose consistent and inconsistent frequency with the response were the same as serum SCC-Ag levels.
The results indicated that CXCL10 is a potential serum biomarker complementing SCC-Ag in prediction of CESC. CXCL10 showed ability in the diagnosis of SCC-Ag negative CESC and the combination of CXCL10 and SCC-Ag inhibited improved performance compared with SCC-Ag alone.
宫颈鳞状细胞癌(CESC)是宫颈癌最常见的组织学类型,也是全球女性死亡的主要原因。虽然鳞状细胞癌抗原(SCC-Ag)被广泛用于检测 CESC,但它的灵敏度和特异性不足以预测疾病。
本研究旨在探讨血清趋化因子(CXC 基序)配体 10(CXCL10)作为检测 CESC 的潜在诊断生物标志物。通过 ELISA 或自动免疫分析法检测 345 名参与者(包括 189 名不同分期的 CESC 患者、75 名宫颈上皮内瘤变患者和 81 名健康个体)的血清 CXCL10 和 SCC-Ag 水平。通过 ROC 曲线分析 CXCL10 和 SCC-Ag 作为单一生物标志物的性能。评估 10 例 CESC 患者在放化疗过程中部分缓解(PR)期间血清 CXCL10 和 SCC-Ag 水平的变化。
这两个标志物在区分 CESC 早期与健康对照组(AUCCXCL10=0.740,AUCSCC-Ag=0.710)和所有 CESC 与健康对照组(AUCCXCL10=0.775,AUCSCC-Ag=0.793)方面具有相似的诊断能力。此外,CXCL10 能够区分宫颈上皮内瘤变与健康对照组(AUCCXCL10=0.727)和 SCC-Ag 阴性的宫颈癌与健康对照组(AUCCXCL10=0.739)。与单独的 SCC-Ag 或 CXCL10 相比,CXCL10 与 SCC-Ag 的联合检测在分析组(健康对照组与所有宫颈癌、健康对照组与宫颈癌早期)中显著提高了 AUC 值。通过联合两种标志物,AUC 分别提高到 0.877(AUCSCC-Ag=0.793,P<0.05)以区分健康对照组与所有 CESC,以及 0.828(AUCSCC-Ag=0.710,P<0.05)以区分健康对照组与 CESC 早期。晚期肿瘤阶段的 CESC 患者与早期肿瘤阶段的 CESC 患者之间的血清 CXCL10 水平存在显著差异(P<0.01)。治疗后有部分缓解的 CESC 患者的血清 CXCL10 水平在治疗过程中显著下降(P=0.013),其与治疗反应的一致性和非一致性频率与 SCC-Ag 水平相同。
研究结果表明,CXCL10 是一种潜在的血清生物标志物,可补充 SCC-Ag 用于预测 CESC。CXCL10 能够诊断 SCC-Ag 阴性的 CESC,与 SCC-Ag 联合使用可提高性能,优于单独使用 SCC-Ag。