基于类器官模型的宫颈癌铂类化疗药物敏感性的免疫组化指标分析与探索

Analysis of chemosensitivity of cervical cancer to platinum drugs by immunohistochemical indices based on organoid model

目的研究免疫组化指标CEA、CK5/6、CK7、Ki-67、p16、p53、p63表达与宫颈癌对铂类等化疗药物敏感性之间的关系。方法选自同济大学附属第十人民医院收治的宫颈癌患者术中肿瘤组织;进行肿瘤化疗药物敏感性检测,运用液体覆盖技术3D细胞培养联合ATP-TCA,评价药物敏感性;检测宫颈癌病理标本免疫组化指标CEA、CK5/6、CK7、Ki-67、p16、p53、p63表达水平;对免疫组化指标表达与宫颈癌对化疗药物的敏感性进行Spearman等级相关分析。结果24例宫颈癌患者的3D肿瘤细胞对紫杉醇+顺铂、顺铂的敏感率最高(65%、60%),对吉西他滨的敏感率较高(38%),对紫杉醇+卡铂、卡铂、奈达铂的敏感率较低(6%、20%、6%),对紫杉醇、多西他赛的敏感率为0%。免疫组化指标Ki-67表达水平与宫颈癌3D细胞对紫杉醇+顺铂的敏感性呈正相关(P<0.05),p63表达水平与宫颈癌3D细胞对紫杉醇+卡铂的敏感性呈负相关(P<0.05),CEA表达水平与宫颈癌3D细胞对吉西他滨敏感性呈负相关(P<0.05),其余指标与化疗药物敏感性无明显相关性。结论基于3D细胞类器官模型,免疫组化指标Ki-67、p63、CEA表达水平可初步预测宫颈癌患者对紫杉醇+顺铂、紫杉醇+卡铂和吉西他滨化疗的敏感性。

Objective To analyze the chemosensitivity of cervical cancer to platinum by immunohistochemical indices based on the organoid model.Methods Tissue samples were collected from 24 patients with cervical cancer undergoing surgical treatment in Shanghai Tenth People's Hospital of Tongji University from March 2018 to January 2020.The chemosensitivity of tumor cells was detected,using liquid overlay technique 3D cell culture combined with ATP-TCA.The expression levels of CEA,CK5/6,CK7,Ki-67,p16,p53 and p63 in cervical cancer were detected with immunohistochemistry.Spearman rank correlation analysis was performed to analyze the correlation of the expression of immunohistochemical indices with the sensitivity of cervical cancer to chemotherapy drugs.Results The sensitivity rates of 3D tumor cells of 24 cervical cancer patients to paclitaxel+cisplatin,cisplatin,gemcitabine,paclitaxel+carboplatin,carboplatin,nedaplatin,paclitaxel and docetaxelwas were 65%,60%,38%,6%,20%,6%,0%and 0%,respectively.The expression level of Ki-67 was positively correlated with the chemosensitivity of cervical cancer to paclitaxel+cisplatin(P<0.05);the expression level of p63 was negatively correlated with the chemosensitivity of cervical cancer to paclitaxel+carboplatin(P<0.05);the expression level of CEA was negatively correlated with the chemosensitivity of cervical cancer to gemcitabine(P<0.05);the other indices were not significantly correlated with the chemosensitivity.Conclusion Based on 3D cell organoid model,the chemosensitivity of cervical cancer patients to paclitaxel+cisplatin,paclitaxel+carboplatin and gemcitabine can be predicted by cancer tissue expression of Ki-67,p63 and CEA,respectively.