VEGF and TWIST1 in a 16‐biomarker immunoprofile useful for prognosis of breast cancer patients

Abstract

This study concerns the expression of biomarkers involved in diverse pathways, such as progression, DNA repair mechanisms and angiogenesis to establish an immunoprofile capable of characterizing sporadic versus familial breast cancers (BCs). The aim was to identify a patient subgroup with a different clinical outcome, which could then be directed towards new targeted therapies. Hierarchical cluster analysis (HCA) was carried out using the immunohistochemical score from tissue microarray sections of an initial cohort of 183 (88 sporadic and 95 familial) patients with invasive BC. For the survival analysis, only those patients with complete follow-up were considered. The HCA revealed a 16-protein immunoprofile, nine of which represent the core, as was also found when familial and sporadic BCs were analysed individually. The 16-biomarker immunoprofile was able to identify a group of patients (Group 1) with a more aggressive tumour phenotype. Survival analyses showed that VEGF /TWIST1 patients with familial BC of Group 1 tended to demonstrate a lower DFS than the VEGF /TWIST1 sporadic BC patients of Group 2 (p = 0.052). Moreover, the entire cohort of VEGF /TWIST1 patients showed a statistically worse DFS than the patients with VEGF /TWIST1 expression (p = 0.034). In conclusion, we found that tumour stratification based on an immunoprofile is useful to predict the patient clinical behaviour. In particular, our study indicates that the clustering of tumors on the basis of this immunoprofile suggests the possibility to differentiate familial from sporadic BCs and to clinically select those patients who are more likely to benefit from inhibition of the VEGF pathway.

NHERF1 and tumor microenvironment: a new scene in invasive breast carcinoma

“…In this study, a panel of factors involved in TME changes such as VEGF, VEGFR1, HIF-1a, TWIST1 and MVD, that have been related to BC progression, aggressiveness and invasion was analyzed [ 6 , 12 , 28 – 30 ]. Further, so as to better characterize this microenvironment, their association with the scaffolding protein NHERF1 and with survival was observed, allowing to identify a possible subgroup of patients that could benefit from a specific therapy.…”

Prognostic value of Kinesin‐4 family genes mRNA expression in early‐stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy

“…As the results showed that, the mechanism might be implicated in several biological processes and signaling pathways, such as DNA damage and repair, transcription and translation process, post‐translation protein modification, cell cycle, carcinogensis genes and pathways ( KARS , EGFR , VEGF , WNT pathway, Hedgehog pathway). It is important to note that the above biological processes and pathways are significantly associated with cancer prognosis . A number of studies have demonstrated the involvement of several of these processes in pancreatic cancer prognosis.…”

“…It is important to note that the above biological processes and pathways are significantly associated with cancer prognosis. [67][68][69][70][71][72][73][74][75] A number of studies have demonstrated the involvement of several of these processes in pancreatic cancer prognosis. For example, the low expression of CHD5 could activate DNA damage response and function as useful biomarker for pancreatic cancer poor clinical outcome.…”

Structure and function of vascular endothelial growth factor and its receptor system

“…In addition, the development of other anti-VEGF-VEGFR drugs such as VEGF-Trap and humanized anti-VEGFR antibodies is consistently ongoing to overcome adverse drug effects. Recent studies suggest that VEGF pathway appears to be useful for prognosis of several cancers patients including breast cancer and is also conducted as the most critical pathway regulating liver and lymph node metastasis of breast cancer ( 60 – 62 ). Therefore, we can use VEGF-VEGFR system as a potential target of new drugs, and more detailed structure-based insightful information regarding the VEGF-VEGFR system is essential to improve the anti-angiogenic therapy for the improved quality of life of cancer patients.…”