Dataset Information

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.

SUBMITTER: Feng A

PROVIDER: S-EPMC4991471 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Feng Anlin A Tu Zhenbo Z Yin Bingjiao B

Oncotarget 20160401 15

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. Fu ...[more]

PMID: 26840258

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Project description:Lung cancer is one of the most common malignancies and the leading cause of cancer‑associated mortality in Korea. A significant amount of effort has been put into the development of new and more effective treatments and biological markers for the prediction of therapeutic responses, which has led to the identification of various genetic changes in cancer, that are the so‑called 'growth drivers' of carcinogenesis. Certain genetic alterations have become new treatment targets, and it has been suggested that different mutations are associated with different clinicopathological characteristics and prognosis. The present study aimed to evaluate the status of the key 'driver' mutation anaplastic lymphoma kinase (ALK) fusion in Korean patients with non‑small cell lung cancer (NSCLC) and its association with clinicopathological characteristics, including the presence of other genetic mutations. The present study also compared different methods for ALK fusion detection, including fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and next‑generation sequencing (NGS) to evaluate which method is the most effective. A total of 482 patients with NSCLC who underwent ALK FISH analysis were evaluated for clinicopathological features, such as age, sex, smoking history, tumor stage, histological subtype, immunohistochemical profile, including ALK and EGFR mutation statuses, and survival. Some ALK FISH‑positive and ‑negative cancers were newly submitted to NGS analysis for DNA and RNA alterations. The ALK fusion‑positive tumors were associated with a younger age, female patients, frequent nodal metastases, advanced stage and shorter survival. Comparing the results of ALK FISH, IHC and NGS analyses, it was concluded that in practice, ALK testing should better be diversified concerning FISH and IHC, and NGS analysis would be a good alternative to FISH, with an additional advantage of being able to concurrently detect different mutations.

Project description:BackgroundThe rapid aging of the population in Japan has been accompanied by an increased rate of surgery for lung cancer among elderly patients. It is thus an urgent priority to map out a treatment strategy for elderly patients with primary lung cancer. Although surgical resection remains standard treatment for early stage non-small-cell lung cancer (NSCLC), it is now essential to confirm the status of epidermal growth factor receptor (EGFR) gene mutations when planning treatment strategies. Furthermore, several studies have reported that EGFR mutations are an independent prognostic marker in NSCLC. However, the relations between age group and the molecular and pathological characteristics of NSCLC remain unclear. We studied the status of EGFR mutations in elderly patients with NSCLC and examined the relations of EGFR mutations to clinicopathological factors and outcomes according to age group.MethodsA total of 388 consecutive patients with NSCLC who underwent complete tumor resection in our hospital from 2006 through 2008 were studied retrospectively. Formalin-fixed, paraffin-embedded tissue sections were used to isolate DNA from carcinoma lesions. Mutational analyses of EGFR gene exons 19, 20, and 21 and KRAS gene exons 12 and 13 were performed by loop-hybrid mobility shift assay, a highly sensitive polymerase chain reaction-based method.ResultsEGFR mutations were detected in 185 (47.7%) and KRAS mutations were detected in 33 (8.5%) of the 388 patients. EGFR mutations were found in a significantly higher proportion of patients younger than 80 years (younger group; 178/359, 49.6%) than in patients 80 years or older (older group; 7/29, 24.1%) (P = 0.008). In contrast, KRAS mutations were more common in the older group (6/29, 20.7%) than in the younger group (27/359, 7.5%) (P = 0.014). The older group showed a trend toward a higher rate of 5-year overall survival among elderly patients with EGFR mutations (100%) than among those with wild-type EGFR (66.2%), but the difference was not significant.ConclusionsOur results suggest that the EGFR status of patients with NSCLC differs between patients 80 years or older and those younger than 80 years. EGFR mutation status might be a prognostic marker in elderly patients with completely resected NSCLC.

Dataset Information

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

Publications

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

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