Abstract
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.
Highlights
Breast cancer is the most commonly diagnosed cancer among women aged 20–60 years, with over 2,000,000 new diagnosed cases every year, worldwide
We checked for potential prognostic factors in triple negative breast cancers (TNBCs): our analysis showed that some immune-related genes were associated with disease-free survival and, may be promising factors for estimating the natural history of the tumour and the chance of disease recurring
We identified several genes whose expression showed a strong positive correlation with disease-free survival in TNBC patients (Fig. 1 and Additional file 1: Fig. S1)
Summary
Breast cancer is the most commonly diagnosed cancer among women aged 20–60 years, with over 2,000,000 new diagnosed cases every year, worldwide. Incidence rates have been stable or even decreased in recent years, this tumour remains the second leading cause of cancer death in women [1, 2]. Difficulty in setting effective therapeutic treatments resides in the phenotypic heterogeneity observed within breast cancer subtypes.
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