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Autophagic protein Beclin 1 serves as an independent positive prognostic biomarker for non-small cell lung cancer.

ABSTRACT: Beclin 1, a key regulator of autophagy, has been found to be aberrantly expressed in a variety of human malignancies. Herein, we employed immunohistochemistry (IHC) to detect the protein expression of Beclin 1 in non-small cell lung cancer (NSCLC) and paired normal adjacent lung tissues, and analyzed its clinicopathological/prognostic significance in NSCLC. Receiver operating characteristic (ROC) curve analysis was utilized to determine a cutoff point (>2 VS. ? 2) for Beclin 1 expression in a training set (n = 105). For validation, the ROC-derived cutoff value was subjected to analysis of the association of Beclin 1 with patients' clinical characteristics and outcome in a testing set (n = 111) and the overall patient cohort (n = 216). Our data showed that Beclin 1 was significantly lower in NSCLC tissues compared with the adjacent normal tissues, negatively associating with tumor recurrence rate (65.8% VS 32.3%; p < 0.001). In the testing set and the overall patient cohort, low expression of Beclin 1 showed significantly inferior overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001) compared to high expression of Beclin 1. In the testing set and the overall patient cohort, the median duration of OS for patients with high and low expression of Beclin 1 was 108 VS. 24.5 months (p < 0.001) and 108 VS. 28 months (p < 0.001), respectively. Furthermore, low expression of Beclin 1 was also a poor prognostic factor within each stage of NSCLC patients. Multivariate analysis identified that Beclin 1 was an independent prognostic factor for NSCLC. Our findings in the present study provided evidence that Beclin 1 may thus emerge as an independent prognostic biomarker in this tumor entity in the future.

SUBMITTER: Zhou W

PROVIDER: S-EPMC3829868 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Autophagic protein Beclin 1 serves as an independent positive prognostic biomarker for non-small cell lung cancer.

Zhou Weihua W Yue Caifeng C Deng Jinyun J Hu Ronghuan R Xu Jie J Feng Long L Lan Qiongyu Q Zhang Wenfeng W Ji Dexiang D Wu Jianbing J Liu Quentin Q Liu Anwen A

PloS one 20131115 11

Beclin 1, a key regulator of autophagy, has been found to be aberrantly expressed in a variety of human malignancies. Herein, we employed immunohistochemistry (IHC) to detect the protein expression of Beclin 1 in non-small cell lung cancer (NSCLC) and paired normal adjacent lung tissues, and analyzed its clinicopathological/prognostic significance in NSCLC. Receiver operating characteristic (ROC) curve analysis was utilized to determine a cutoff point (>2 VS. ≤ 2) for Beclin 1 expression in a tr ...[more]

PMID: 24260370

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Project description:Background and objectiveLiver cancer is a malignancy with a poor prognosis. G protein signaling modulator 2 is mainly related to cell division and cell cycle regulation. In this review, the relationship between G protein signaling modulator 2 and clinical characteristics of patients with liver cancer has been explored, especially with respect to its prognostic value.MethodsG protein signaling modulator 2 messenger RNA expression and clinicopathological characteristics of patients with liver cancer were obtained from The Cancer Genome Atlas. The expression level of G protein signaling modulator 2 RNA-Seq was validated by using Gene Expression Omnibus. Chi-square test was performed to evaluate the relationship between G protein signaling modulator 2 expression and clinical characteristics. The threshold value of G protein signaling modulator 2 in the diagnosis of liver cancer was evaluated by a receiver-operating characteristic curve. Cox regression analysis and Kaplan-Meier curves were performed to evaluate the relationship between G protein signaling modulator 2 and liver cancer prognosis, which included overall and residual-free survival, and explored the prognostic value of G protein signaling modulator 2. Liver cancer survival analyses were validated by using the data of G protein signaling modulator 2 RNA-Seq from the International Cancer Genome Consortium.ResultsThe expression level of G protein signaling modulator 2 messenger RNA was remarkably higher in liver cancer than that in healthy tissues (P < 2.2 × e-16), which was also validated by data from the GSE14520 database. In addition, high G protein signaling modulator 2 expression significantly correlated with histological grade (P = .020), vital status (P < .001), clinical (P = .001), and T stage (P = .001). The receiver-operating characteristic curves showed G protein signaling modulator 2 to be an advantageous diagnostic molecule for liver cancer (area under curve = 0.893). Furthermore, the results of Cox analysis and Kaplan-Meier curves suggested that the upregulation of G protein signaling modulator 2 expression is linked to poor prognosis and G protein signaling modulator 2 messenger RNA could be an independent predictor for liver cancer, which was validated by data from the International Cancer Genome Consortium database.ConclusionsG protein signaling modulator 2 messenger RNA was overexpressed in liver cancer, and G protein signaling modulator 2 is an independent prognostic factor. G protein signaling modulator 2 is expected to be a treatment target for cancer.

Project description:BackgroundRoutine clinical surveillance involves serial radiographic imaging following radical surgery in localized non-small cell lung cancer (NSCLC). However, such surveillance can detect only macroscopic disease recurrence and is frequently inconclusive. We investigated if detection of ctDNA before and after resection of NSCLC identifies the patients with risk of relapse, and furthermore, informs about response to management.MethodsWe recruited a total of 77 NSCLC patients. A high-throughput 127 target-gene capture technology and a high-sensitivity circulating single-molecule amplification and resequencing technology (cSMART) assay were used to detect the somatic mutations in the tumor tissues as well as the plasma of NSCLC patients before and after surgery to monitor for minimal residual disease (MRD). Kaplan-Meier and Cox regression analysis were performed to evaluate the relapse-free survival (RFS) and overall survival (OS) of patients with predictor variables.ResultsPatients with a higher stage (III/IV) and preoperative ctDNA-positive status demonstrated a significant 2.8-3.4-fold risk and 3.8-4.0-fold risk for recurrence and death, respectively. Preoperative ctDNA-positive patients associated with a lower RFS (HR = 3.812, p = 0.0005) and OS (HR = 5.004, p = 0.0009). Postoperative ctDNA-positive patients also associated with a lower RFS (HR = 3.076, p = 0.0015) and OS (HR = 3.195, p = 0.0053). Disease recurrence occurred among 63.3% (19/30) of postoperative ctDNA-positive patients. Most of these patients 89.5% (17/19) had detectable ctDNA within 2 weeks after surgery and was identified in advance of radiographic findings by a median of 12.6 months.ConclusionAdvanced stage and preoperative ctDNA-positive are strong predictors of RFS and OS in localized NSCLC patients undergoing complete resection. Postoperative detection of ctDNA increases chance to detect early relapse, thus can fulfill an important role in stratifying patients for immediate further treatment with adjuvant and neoadjuvant therapy.

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Autophagic protein Beclin 1 serves as an independent positive prognostic biomarker for non-small cell lung cancer.

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Autophagic protein Beclin 1 serves as an independent positive prognostic biomarker for non-small cell lung cancer.

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