Clinicopathological significance of protein disulphide isomerase A3 and phosphorylated signal transducer and activator of transcription 3 in cervical carcinoma

Asmaa Abdullatif, Aziza E. Abdelrahman, Adel Bakry, Shimaa Gharieb, Mohamed S H Ramadan, Mohamed A. Wasfy, Abdelfatah H. Abdelwanis, Enas M. Fouad
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Abstract

Introduction Death in cervical cancer patients is usually due to invasion and metastasis due to the aggressive nature of the tumour. Therefore, it is critical to identify potent therapeutic targets and prognostic markers to detect high-risk patients. Material and methods We assessed the immunohistochemical expression of protein disulphide isomerase A3 (PDIA3) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in 50 cases of cervical carcinoma, and we investigated their association with clinicopathological characteristics. Results High PDIA3 was detected in 50% of cases, and statistical analysis revealed a positive correlation between high PDAI3 expression and tumour grade (p < 0.001) and large tumour size (p = 0.010), depth of stromal invasion (p = 0.017), lymph-vascular invasion (p = 0.005), parametrial invasion (p < 0.001), nodal metastasis (p < 0.001), and higher International Federation of Gynaecology and Obstetrics stages (p < 0.001). Positive nuclear expression of p-STAT3 was detected in 44% of cases and showed significant association with histological grade (p = 0.036), tumour stage (p = 0.021), nodal metastasis (p = 0.020), and parametrial invasion (p = 0.045); statistical analysis of the patient’s survival data revealed that shorter overall survival and disease-free survival, S, were associated with high PDIA3 expression and positive p-STAT3 immunoexpression. Conclusions The high expression of PDIA3 and p-STAT3 was related to highly aggressive cervical carcinoma with poor prognosis, and high risk of recurrence after the standardised protocol of treatment. Hence, both PDIA3 and p-STAT3 could be considered as novel biomarkers for tumour progression and promising targets in the management of cervical carcinoma patients.
宫颈癌中蛋白二硫异构酶 A3 和磷酸化信号转导和转录激活因子 3 的临床病理学意义
导言 宫颈癌患者的死亡通常是由于肿瘤的侵袭性和转移性。因此,确定有效的治疗靶点和预后标志物以检测高危患者至关重要。材料与方法 我们评估了 50 例宫颈癌患者中蛋白二硫化物异构酶 A3(PDIA3)和磷酸化信号转导和激活剂转录 3(p-STAT3)的免疫组化表达,并研究了它们与临床病理特征的关系。结果 50%的病例检测到 PDIA3 高表达,统计分析显示 PDAI3 高表达与肿瘤分级(p < 0.001)、肿瘤体积大(p = 0.统计分析显示,PDAI3高表达与肿瘤分级(p < 0.001)、肿瘤体积大(p = 0.010)、基质浸润深度(p = 0.017)、淋巴管浸润(p = 0.005)、宫旁浸润(p < 0.001)、结节转移(p < 0.001)和国际妇产科联盟分期较高(p < 0.001)呈正相关。44%的病例检测到p-STAT3核阳性表达,并与组织学分级(p = 0.036)、肿瘤分期(p = 0.021)、结节转移(p = 0.020)和宫旁侵犯(p = 0.045)显著相关;对患者生存数据的统计分析显示,较短的总生存期和无病生存期(S)与PDIA3高表达和p-STAT3免疫阳性表达相关。结论 PDIA3 和 p-STAT3 的高表达与预后不良的高侵袭性宫颈癌以及标准化治疗方案后的高复发风险有关。因此,PDIA3 和 p-STAT3 可被视为肿瘤进展的新型生物标记物,是治疗宫颈癌患者的有希望的靶点。
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