Trop-2是胰腺腺癌中一个普遍存在且很有前景的靶点。

Trop-2 is a ubiquitous and promising target in pancreatic adenocarcinoma.

作者信息

Mas L, Cros J, Svrcek M, Van Laethem J L, Emile J F, Rebours V, Nicolle R, Bachet J B

机构信息

Department of Hepato-Gastroenterology and Digestive Oncology, Pitié Salpêtrière Hospital, APHP, 47-83 Boulevard de l'Hôpital, Paris 75013, France; Sorbonne University, UPMC University, 15-21 Rue de l'École de Médecine, Paris 75006, France.

Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Biomédicale Bichat Beaujon (CRI)/INSERM U1149, Clichy, France; Department of Pathology, Beaujon Hospital, AP-HP, 100 Boulevard du Général Leclerc, Clichy 92110, France.

出版信息

Clin Res Hepatol Gastroenterol. 2023 Apr;47(4):102108. doi: 10.1016/j.clinre.2023.102108. Epub 2023 Mar 5.

DOI:10.1016/j.clinre.2023.102108

PMID:36878461

Abstract

BACKGROUND

Trop-2 is overexpressed in tumor cells of various cancers, including pancreatic ductal adenocarcinoma (PDAC), and has emerged as a potent therapeutic target. We evaluated Trop-2 expression both at the transcriptomic and protein levels, and its correlation with tumor features and patients' outcomes in a large cohort of PDAC.

METHODS

We included patients undergoing pancreatic resection for PDAC in 5 academic hospitals in France and Belgium. Transcriptomic profiles were obtained from FFPE tissue samples, with paired primary -25and metastatic lesions when available. Protein expression was evaluated by immunohistochemistry (IHC) using tissue micro-arrays.

RESULTS

495 patients (male 54%, median age 63 years) were included between 1996 and 2012. Trop-2 mRNA expression was significantly associated to tumor cellularity, but no association with survival nor with any clinical or pathological features was observed, with tumor cells showing an overall high expression among every subgroup. Trop-2 mRNA expression was maintained between primary and metastatic lesion in all 26 paired samples evaluated. In 50 tumors assessed by IHC, 30%, 68% and 2% harbored a high, medium, or low Trop-2 expression score, respectively. Trop-2 staining was significantly associated to mRNA expression, but not to survival or any pathological features.

CONCLUSIONS

Our results suggest Trop-2 overexpression as a ubiquitous marker of PDAC tumor cells and thus a promising therapeutic target to evaluate in these patients.

摘要

背景

Trop-2在包括胰腺导管腺癌（PDAC）在内的多种癌症的肿瘤细胞中过度表达，并已成为一个有效的治疗靶点。我们在一大群PDAC患者中评估了Trop-2在转录组和蛋白质水平的表达，及其与肿瘤特征和患者预后的相关性。

方法

我们纳入了法国和比利时5家学术医院中因PDAC接受胰腺切除术的患者。转录组谱从福尔马林固定石蜡包埋（FFPE）组织样本中获得，如有可用的配对原发性和转移性病变样本则一并获取。使用组织微阵列通过免疫组织化学（IHC）评估蛋白质表达。

结果

1996年至2012年间共纳入495例患者（男性占54%，中位年龄63岁）。Trop-2 mRNA表达与肿瘤细胞密度显著相关，但未观察到与生存率以及任何临床或病理特征相关，在每个亚组中肿瘤细胞总体上均呈现高表达。在评估的所有26对配对样本中，原发性和转移性病变之间的Trop-2 mRNA表达保持一致。在通过IHC评估的50个肿瘤中，分别有30%、68%和2%的肿瘤具有高、中或低Trop-2表达评分。Trop-2染色与mRNA表达显著相关，但与生存率或任何病理特征无关。