High-mobility group nucleosome-binding protein 1 is a novel clinical biomarker in non-small cell lung cancer

Abstract

The involvement of alarmin high-mobility group nucleosome-binding protein 1 (HMGN1) in non-small cell lung cancer (NSCLC) is unknown. To address the presence of HMGN1 in the serum of different stages of NSCLC patients and healthy controls, we enrolled a consecutive sample of adult serum at diagnosis and correlated it with clinicopathologic outcomes. A total of 100 NSCLC patients and 23 healthy volunteers were enrolled from January 2012 through December 2013. Serum HMGN1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Additionally, HMGN1 levels in 50 NSCLC patients with early-stage disease who received curative pneumonectomy were correlated with survivals. Kaplan-Meier plots were used to analyze the data. The patients with NSCLC were characterized by significantly higher serum levels of HMGN1 (0.4585 ± 0.0640 ng/ml) compared to those in healthy controls (0.3578 ± 0.0304 ng/ml). The serum HMGN1 levels were 0.4027 ± 0.0271 ng/ml, 0.4604 ± 0.0328 ng/ml, 0.5408 ± 0.0459 ng/ml, and 0.4213 ± 0.0341 ng/ml in patients with TNM stages I, II, IV, and IV, respectively (p < 0.001). There were significant differences among four groups (p < 0.001). Additionally, a positive correlation between serum HMGN1 and tumor stage was found in local disease, while serum HMGN1 level in metastatic NSCLC patients was significantly decreased. The Kaplan-Meier plots showed that patients with high serum HMGN1 had a poorer overall survival (OS) after curative pneumonectomy than those with low serum HMGN1 (p = 0.019). Inflammation triggered by alarmins plays a role in NSCLC pathogenesis. HMGN1 can serve as a useful clinical parameter for evaluating disease progression and predicting the outcomes for early-stage patients with NSCLC undergoing pneumonectomy.

Soluble Toll-like receptor 4 is a potential serum biomarker in non-small cell lung cancer

“…Taken together, our present work, as well as our previous work on HMGN1 [14], suggested that the alarmin system, which consists of alarmins and their soluble or membrane-bound receptors, hold great potential as ideal biomarkers to predict prognosis, monitor disease progression, or even access therapeutic effects of NSCLC patients.…”

“…The involvement of soluble TLR4 (sTLR4) in NSCLC has not been fully elucidated. Notably, high-mobility group nucleosome-binding protein 1 (HMGN1) and HMG box 1 (HMGB1), two major endogenous ligands of TLR4, have been identified as biomarkers of NSCLC [12–14], indicating that serum sTLR4 may also be of clinical significance in NSCLC. Lan et al recently reported that serum sTLR4 before radiotherapy may be a potential biomarker of radiation-induced pneumonia in patients with local advanced NSCLC [15].…”

Biological Functions of HMGN Chromosomal Proteins

“…In non-small cell lung cancer (NSCLC) patients, the levels of HMGN1 in the serum were correlated with overall survival after curative pneumonectomy. Likewise, the levels of HMGN1 in the serum of NSCLC individuals were higher in non-metastatic stages (I-III) as compared to the metastatic stage (IV), suggesting that HMGN1 can serve as a biomarker for early stages of NSCLC [49]. Leukemic B cells from patients with chronic lymphoblastic leukemia express HMGN2 on their surface; the HMGN2 variant acts as an autoantigen and contributes to the development of autoimmune hemolytic anemia [50].…”

Increased expression of high-mobility group nucleosomal-binding domain 2 protein in various tumor cell lines

“…The function of these proteins in transcription, DNA repair and cancer progression have been partly established (3,4,17,18). The results of recent studies have demonstrated that HMGN1 may be a promising clinical biomarker for several types of cancer (19,20). Similarly, the expression of HMGN5 (previously known as NSBP1) is highly regulated in various types of human cancer, including prostate, bladder, breast, lung and clear-cell renal-cell carcinoma (21).…”