Marchetti Paolo, Antonov Alexey, Anemona Lucia, Vangapandou Chaitania, Montanaro Manuela, Botticelli Andrea, Mauriello Alessandro, Melino Gerry, Catani M Valeria
Oncology Unit, Department of Clinical and Molecular Medicine, University of Rome La Sapienza, 00185, Rome, Italy.
MRC Toxicology Unit, University of Cambridge, Cambridge, CB2 1QR, UK.
Discov Oncol. 2021 Mar 10;12(1):6. doi: 10.1007/s12672-021-00401-0.
Breast cancer (BC) is the second leading cause of cancer death in women worldwide, and settings of specific prognostic factors and efficacious therapies are made difficult by phenotypic heterogeneity of BC subtypes. Therefore, there is a current urgent need to define novel predictive genetic predictors that may be useful for stratifying patients with distinct prognostic outcomes. Here, we looked for novel molecular signatures for triple negative breast cancers (TNBCs). By a bioinformatic approach, we identified a panel of genes, whose expression was positively correlated with disease-free survival in TNBC patients, namely IL18R1, CD53, TRIM, Jaw1, LTB, and PTPRCAP, showing specific immune expression profiles linked to survival prediction; most of these genes are indeed expressed in immune cells and are required for productive lymphocyte activation. According to our hypothesis, these genes were not, or poorly, expressed in different TNBC cell lines, derived from either primary breast tumours or metastatic pleural effusions. This conclusion was further supported in vivo, as immuno-histochemical analysis on biopsies of TNBC invasive ductal carcinomas highlighted differential expression of these six genes in cancer cells, as well as in intra- and peri-tumoral infiltrating lymphocytes. Our data open to the possibility that inter-tumour heterogeneity of immune markers might have predictive value; further investigations are recommended in order to establish the real power of cancer-related immune profiles as prognostic factors.
乳腺癌(BC)是全球女性癌症死亡的第二大主要原因,而BC亚型的表型异质性使得确定特定的预后因素和有效治疗方法变得困难。因此,当前迫切需要确定新的预测性基因标志物,这些标志物可能有助于对具有不同预后结果的患者进行分层。在此,我们寻找三阴性乳腺癌(TNBC)的新分子特征。通过生物信息学方法,我们鉴定出一组基因,其表达与TNBC患者的无病生存率呈正相关,即IL18R1、CD53、TRIM、Jaw1、LTB和PTPRCAP,这些基因显示出与生存预测相关的特定免疫表达谱;这些基因中的大多数确实在免疫细胞中表达,并且是有效的淋巴细胞激活所必需的。根据我们的假设,这些基因在源自原发性乳腺肿瘤或转移性胸腔积液的不同TNBC细胞系中未表达或表达不佳。体内研究进一步支持了这一结论,因为对TNBC浸润性导管癌活检组织的免疫组织化学分析突出了这六个基因在癌细胞以及肿瘤内和肿瘤周围浸润淋巴细胞中的差异表达。我们的数据揭示了免疫标志物的肿瘤间异质性可能具有预测价值的可能性;建议进一步研究以确定癌症相关免疫谱作为预后因素的实际作用。