The effect of HMGB1 on the clinicopathological and prognostic features of non-small cell lung cancer

Abstract

Several studies have assessed the diagnostic and prognostic values of high mobility group protein box 1 (HMGB1) expression in non-small cell lung cancer (NSCLC), but these results remain controversial. The purpose of this study was to perform a meta-analysis of the gene microarray analyses of datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to evaluate the association of HMGB1 expression with the clinicopathological and prognostic features of patients with NSCLC. Furthermore, we investigated the underlying molecular mechanisms by bioinformatics analysis. Twenty relevant articles involving 2651 patients were included in this meta-analysis; the HMGB1 expression in NSCLC tissues was significantly higher than that in the healthy non-cancer control tissues. We also found an indication by microarray analysis and meta-analysis that HMGB1 expression was associated with the cancer TNM Staging System. In terms of prognostic features, a survival analysis from KM-Plotter tool revealed that the high HMGB1 expression group exhibited poorer survival in lung adenocarcinoma (ADC) and overall NSCLC patients. The survival and disease-free analyses from TCGA datasets also showed that HMGB1 mainly affected the development of patients with ADC. Therefore, we focused on how HMGB1 affected the prognosis and development of ADC using bioinformatics analyses and detected that the mitogen-activated protein kinases (MAPK), apoptosis and cell cycle signaling pathways were the key pathways that varied during HMGB1 up-regulation in ADC. Moreover, various genes such as PLCG2, the phosphatidylinositol-4, 5-bisphosphate 3-kinase superfamily (PI3Ks), protein kinase C (PKC) and DGKZ were selected as hub genes in the gene regulatory network. Our results indicated that HMGB1 is a potential biomarker to predict progression and survival of NSCLC, especially of ADC types.

HMGB1 is negatively correlated with the development of endometrial carcinoma and prevents cancer cell invasion and metastasis by inhibiting the process of epithelial-to-mesenchymal transition

“…Moreover, HMGB1 was negatively related to the clinical and pathological characteristics of endometrial cancer. In the current study, the elevated expression levels of HMGB1 in both tissues and sera of patients are more commonly found in solid tumors, including hepatocellular,23 ovarian,24 colorectal25 and non-small cell lung cancers 26. The overexpression of HMGB1 was positively correlated with the prognosis of patients with various types of cancer 27.…”

Topological demarcation by HMGB2 is disrupted early upon senescence entry across cell types and induces CTCF clustering

“…HMGB1 and HMGB2 are overexpressed across a large number of cancer types (TCGA data; http://www.cbioportal.org/; Gao et al, 2013), and HMGB1 overexpression has been directly linked to the proliferative capacity and metastasis of malignant cells (Tang et al, 2010) and of lung adenocarcinoma in particular (Feng et al, 2016). Hence, we sought to investigate how HMGB2mediated deregulation of chromosome organization might affect lung adenocarcinoma patient lines.…”

Hmgb1: A Potential Therapeutic Target for Non-Small Cell Lung Cancer

“…Anti-HMGB1 Antibody Extracellular HMGB1 Leukemia [8] Ethyl Pyruvate Extracellular HMGB1 Hepatocarcinoma [11] Glycyrrhizin Extracellular HMGB1 Melonoma [8] Oxaliplatin Intracellular HMGB1 Colon Carcinoma [12,13] Quercetin Extracellular HMGB1 Breast Cancer [9] HMGB1 in NSCLC As the previous studies showed, HMGB1 over expressed in NSCLC and affected the prognosis and development of NS-CLC patients. Because of the rare mutation of HMGB1 in NSCLC patients [3] , we considered HMGB1 as a better targeting bio-marker for NSCLC than TKs. However, there's no research target HMGB1 as a therapy strategy for treatment of NSCLC patients.…”

“…A major part of researches have revealed that over expression of HMGB1 triggers cell differentiation, cell migration and cancer metastasis after being release into the extracellular space, thus it could promote cancer development and resistance [2] . Our previous study has already showed that HMGB1 over expressed in NSCLC and intensely affect the survival of NSCLC patients [3] , so this review focused on the therapeutic target value of HMGB1 for NSCLC in current researches.…”