Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer.

Pretreatment serum squamous cell carcinoma antigen (SCCA) is a prognostic biomarker in women with cervical cancer. SCCA has not been evaluated as an early indicator of response to chemoradiation therapy (CRT). The molecular role of the two SCCA isoforms, SCCA1 (SERPINB3) and SCCA2 (SERPINB4), in cervical cancer is unknown. We hypothesised that changes in serum SCCA during definitive CRT predicts treatment response, and that SCCA1 mediates radiation resistance. Patients treated with definitive CRT for cervical squamous carcinoma with serum SCCA measured were included. SCCA immunohistochemistry was performed on tumour biopsies. Post-treatment FDG-PET/CT, recurrence, and overall survival were recorded. Radiation response of cervical tumour cell lines after SCCA1 expression or CRISPR/Cas9 knockout was evaluated by clonogenic survival assay. Persistently elevated serum SCCA during definitive CRT was an independent predictor of positive post-therapy FDG-PET/CT (P=0.043), recurrence (P=0.0046) and death (P=0.015). An SCCA1-expressing vector increased radioresistance, while SCCA knock out increased radiosensitivity of cervical tumour cell lines in vitro. Early response assessment with serum SCCA is a powerful prognostic tool. These findings suggest that escalation of therapy in patients with elevated or sustained serum SCCA and molecular targeting of SCCA1 should be considered.

治疗前血清鳞状细胞癌抗原（SCCA）是宫颈癌女性的一种预后生物标志物。SCCA尚未被评估为放化疗（CRT）反应的早期指标。两种SCCA异构体，SCCA1（丝氨酸蛋白酶抑制剂B3）和SCCA2（丝氨酸蛋白酶抑制剂B4）在宫颈癌中的分子作用尚不清楚。我们假设在确定性CRT期间血清SCCA的变化可预测治疗反应，并且SCCA1介导放射抗性。 纳入接受确定性CRT治疗且测量了血清SCCA的宫颈鳞状细胞癌患者。对肿瘤活检进行SCCA免疫组化。记录治疗后的氟脱氧葡萄糖 - 正电子发射断层扫描/计算机断层扫描（FDG - PET/CT）、复发情况和总生存期。通过克隆形成存活试验评估SCCA1表达或CRISPR/Cas9敲除后宫颈肿瘤细胞系的放射反应。 在确定性CRT期间血清SCCA持续升高是治疗后FDG - PET/CT阳性（P = 0.043）、复发（P = 0.0046）和死亡（P = 0.015）的独立预测因子。表达SCCA1的载体增加了放射抗性，而SCCA敲除则增加了体外宫颈肿瘤细胞系的放射敏感性。 用血清SCCA进行早期反应评估是一种强有力的预后工具。这些发现表明，对于血清SCCA升高或持续升高的患者应考虑强化治疗，并考虑对SCCA1进行分子靶向治疗。