Comparative Analysis of Putative Prognostic and Predictive Markers in Neuroblastomas: High Expression of PBX1 Is Associated With a Poor Response to Induction Therapy

Abstract

The survival rate for patients with high-risk neuroblastomas remains poor despite new improvements in available therapeutic modalities. A detailed understanding of the mechanisms underlying clinical responses to multimodal treatment is one of the important aspects that may provide precision in the prediction of a patient's clinical outcome. Our study was designed as a detailed comparative analysis of five selected proteins (DDX39A, HMGA1, HOXC9, NF1, and PBX1) in one cohort of patients using the same methodical approaches. These proteins were already reported separately as related to the resistance or sensitivity to retinoids and as useful prognostic markers of survival probability. In the cohort of 19 patients suffering from high-risk neuroblastomas, we analyzed initial immunohistochemistry samples obtained by diagnostic biopsy and post-induction samples taken after the end of induction therapy. The expression of DDX39A, HMGA1, HOXC9, and NF1 showed varied patterns with almost no differences between responders and non-responders. Nevertheless, we found very interesting results for PBX1: non-responders had significantly higher expression levels of this protein in the initial tumor samples when compared with responders; this expression pattern changed inversely in the post-induction samples, and this change was also statistically significant. Moreover, our results from survival analyses reveal the prognostic value of PBX1, NF1, and HOXC9 expression in neuroblastoma tissue. In addition to the prognostic importance of PBX1, NF1, and HOXC9 proteins, our results demonstrated that PBX1 could be used for the prediction of the clinical response to induction chemotherapy in patients suffering from high-risk neuroblastoma.

Diagnostic utility of cytology smears and cell block in adrenal lesions

“…Segmental chromosomal aberrations like 1p deletion, 11q deletion and gain of 17q are associated with clinically aggressive disease. IHC expression of some selected proteins, PBX1 and NF1 have been shown to be useful as predictive factors following chemotherapy 18 . Cellblock provides material to perform these ancillary tests.…”

PBX1: a TALE of two seasons—key roles during development and in cancer

“…Sexual developmental defects; CAKUTHED (Mary et al, 2022) Endometrial Carcinoma: Tumor suppressor (Guo et al, 2023) Ovarian Cancer: Oncogene (Park et al, 2008), chemoresistance (Jung et al, 2016) Prostate Cancer: Proliferation (Kikugawa et al, 2006;Liu et al, 2019b) Renal Clear Cell Carcinoma: Cell proliferation via JAK2/STAT3 signaling (Wei et al, 2018) Bladder Cancer: Cell growth, invasion, EMT (Zhao et al, 2022) Gastrointestinal system/ digestive tract Gut aplasia in Pbx1 −/− mice (Selleri et al, 2001) Gastric Carcinoma: potential oncogene (upregulation of miR650 and EMT) (Liu et al, 2021); potential tumor suppressor (upregulation of its PBXIP1 inhibitor) (He et al, 2017) Colorectal Cancer: Metastasis inhibition (Dai et al, 2023) Mouse model of hepatocellular carcinoma: tumor suppressor (upregulation of its PBXIP1 inhibitor) (Xu et al, 2013) Pancreas and pancreatic islands development (Kim et al, 2002) Diabetes mellitus (suggested) (Kim et al, 2002) Lung Lungs development (Li et al, 2014) Non-Small Cell Lung Cancer: Proliferation promotion (Lin et al, 2022) or tumor suppression (Sun et al, 2023) Lymphangioleiomyomatosis: cell survival by inducing expression of antiapoptotic genes (Olatoke et al, 2023) Lung hypoplasia (Mary et al, 2022) Brain Differentiation of olfactory bulb, mesencephalic and midbrain dopaminergic neurons (Sgadò et al, 2012;Remesal et al, 2020); hindbrain segmentation through control of RA synthesis (Vitobello et al, 2011) Brain cancer. Neuroblastoma: higher expression levels in the initial tumor samples compared with responders (Veselska et al, 2019); Glioma: tumor suppressor role) (van Vuurden et al, 2014) Parkinson: reduced levels in dopaminergic neurons (Villaescusa et al, 2016) Other ectoderm derivatives Epithelial cells: Corneal morphogenesis (Murphy et al, 2010); modulation of body-site-specific epidermal barrier (seen with Pbx1 epidermal-specific null mice), auditory sensory epithelium (Li et al, 2020b) Oral squamous cell carcinoma: Oncogene…”