Mallmann Michael R, Tamir Sina, Alfter Katharina, Ratiu Dominik, Quaas Alexander, Domroese Christian M
Faculty of Medicine, University of Cologne, 50931 Cologne, Germany.
Department of Obstetrics and Gynecology, University of Cologne, 50931 Cologne, Germany.
Cancers (Basel). 2024 May 6;16(9):1787. doi: 10.3390/cancers16091787.
(1) Background: There is a huge unmet clinical need for novel treatment strategies in advanced and recurrent cervical cancer. Several cell membrane-bound molecules are up-regulated in cancer cells as compared to normal tissue and have revived interest with the introduction of antibody-drug conjugates (ADCs). (2) Methods: In this study, we characterize the expression of 10 potential ADC targets, TROP2, mesotheline, CEACAM5, DLL3, folate receptor alpha, guanylatcyclase, glycoprotein NMB, CD56, CD70 and CD138, on the gene expression level. Of these, the three ADC targets TROP2, CEACAM5 and CD138 were further analyzed on the protein level. (3) Results: TROP2 shows expression in 98.5% (66/67) of cervical cancer samples. CEACAM5 shows a stable gene expression profile and overall, 68.7% (46/67) of cervical cancer samples are CEACAM-positive with 34.3% (23/67) of cervical cancer samples showing at least moderate or high expression. Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) Conclusions: TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients.
（1）背景：对于晚期和复发性宫颈癌的新型治疗策略，存在巨大未满足的临床需求。与正常组织相比，几种细胞膜结合分子在癌细胞中上调，并且随着抗体药物偶联物（ADC）的引入而重新引起了人们的兴趣。（2）方法：在本研究中，我们在基因表达水平上表征了10种潜在ADC靶点（TROP2、间皮素、癌胚抗原相关细胞黏附分子5、DLL3、叶酸受体α、鸟苷酸环化酶、糖蛋白NMB、CD56、CD70和CD138）的表达。其中，对三种ADC靶点TROP2、癌胚抗原相关细胞黏附分子5和CD138在蛋白质水平上进行了进一步分析。（3）结果：TROP2在98.5%（66/67）的宫颈癌样本中表达。癌胚抗原相关细胞黏附分子5显示出稳定的基因表达谱，总体而言，68.7%（46/67）的宫颈癌样本为癌胚抗原相关细胞黏附分子阳性，34.3%（23/67）的宫颈癌样本显示至少中度或高表达。总体而言，73.1%（49/67）的宫颈癌样本为CD138阳性，38.8%（26/67）的宫颈癌样本显示至少中度或高表达。（4）结论：TROP2、癌胚抗原相关细胞黏附分子5或CD138似乎适合进一步的临床研究，此处呈现的数据可能用于指导晚期和复发性宫颈癌患者使用ADC的进一步临床试验。
