Secretomes are a potential source of molecular targets for cancer therapies and indicate that APOE is a candidate biomarker for lung adenocarcinoma metastasis

Liu, Zan; Gao, Yuan; Hao, Fengxia; Lou, Xiaomin; Zhang, Xiuwei; Li, Yang; Wu, Di; Xiao, Ting; Yang, Lingzhi; Li, Qingchang; Qiu, Xueshan; Wang, Enhua

doi:10.1007/s11033-014-3641-4

Cited by 14 publications

(9 citation statements)

References 37 publications

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“…Therefore, it is essential for cholesterol metabolism. While reductions in APOE levels or function (by genetic variation) can cause cardiac and neurological (Alzheimer's disease) manifestations, elevated blood levels of APOE have been associated with various types of malignancies [28,[41][42][43][44]. In fact based on the data presented here, it seems that APOE upregulation may occur very early in oncogenic development to help support and maintain the abnormal cells.…”

Section: Discussionmentioning

confidence: 64%

Proteomic profiling of human plasma identifies apolipoprotein E as being associated with smoking and a marker for squamous metaplasia of the lung

et al. 2015

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Biomarkers to identify subjects at high-risk for developing lung cancer will revolutionize the disease outlook. Most biomarker studies have focused on patients already diagnosed with lung cancer and in most cases the disease is often advanced and incurable. The objective of this study was to use proteomics to identify a plasma biomarker for early detection of lung lesions that may subsequently be the harbinger for cancer. Plasma samples were obtained from subjects without lung cancer grouped as never, current, or ex-smokers. An iTRAQ-based proteomic analysis was performed on these pooled plasma samples. We identified 31 proteins differentially abundant in current smokers or ex-smokers relative to never smokers. Western blot and ELISA analyses confirmed the iTRAQ results that demonstrated an increase of apolipoprotein E (APOE) in current smokers as compared to both never and ex-smokers. There was a strong and significant correlation of the plasma APOE levels with development of premalignant squamous metaplasia. Additionally, we also showed that higher tissue levels of APOE are seen with squamous metaplasia, supporting a direct relationship. Our analysis reveals that elevated plasma APOE is associated with smoking, and APOE is a novel predictive protein biomarker for early morphological changes of squamous metaplasia in the lung.

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Section: Discussionmentioning

confidence: 64%

Proteomic profiling of human plasma identifies apolipoprotein E as being associated with smoking and a marker for squamous metaplasia of the lung

et al. 2015

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“…APOE has been gaining attention due to its prognostic value in various cancers, including OSCC. While this gene is associated with nerve degeneration and Alzheimer disease, it is also involved in regulation of cell growth, differentiation, and immune responses (Oue et al 2004; Liu et al 2014; Luo et al 2016). In a recent report, Jayakar et al (2017) presented an association of elevated APOE protein expression in highly invasive oral tumors but a significant reduction in cell invasion after APOE knockdown.…”

Section: Discussionmentioning

confidence: 99%

Altered Immune-Related Gene Expressions Indicate Oral Cancer Nodal Disease

Liu

Zhu

et al. 2018

J Dent Res

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Lymph nodal disease (LN+) is the most significant prognostic factor of oral squamous cell carcinoma (OSCC). Current risk indicator(s) for guiding elective neck dissection (END) is insufficient for clinically node-negative (cN0) patients, resulting in under- or overtreatment. While the role of immunological events in tumorigenesis and metastasis is evident, the prognostic implication in OSCC remains unclear. The study objective was to investigate large-scale immune-related gene expression and determine its prognostic value on node-free survival (NFS). We analyzed patients who received intent-to-cure surgery with at least 3 y of follow-up and known outcome of LN through a pan-Canadian surgical trial. Total RNA was extracted from surgical tissues with >70% tumor content and analyzed on a 730-gene panel (NanoString nCounter® PanCancer Immune Panel). We first profiled gene expression in a fresh-frozen (FF) discovery set to identify differentially expressed (DE) genes, which were then used in unsupervised clustering analysis to identify patient subgroups. The prognostic value of the identified DE genes was then validated on formalin-fixed, paraffin-embedded (FFPE) samples. A total of 177 RNA samples were derived from 89 FF and 88 FFPE surgical tissues, of which 45 (51%) and 40 (45%), respectively, were from patients who developed LN+. We identified 6 DE genes overexpressed in LN+ tumors (false discovery rate <0.001; log fold change >1). Clustering analysis separated the patients into 2 subgroups (CM1, CM2), with CM2 exhibiting significantly increased expression and worse 5-y NFS rate (28%; P < 0.001). The prognostic value of these 6 candidate genes was validated on FFPE samples, which were also separated into 2 distinct prognostic groups, confirming the association between increased gene expression and poor 5-y NFS (CM1, 70.3%; CM2, 43.3%; P = 0.01). This is the first study identifying a panel of immune-related genes associated with NFS that can potentially be used clinically stratifying the risk of LN+ at the time of OSCC diagnosis.

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“…APOE has also been demonstrated to be involved in innate immune modulation, which could be a target to enhance the efficacy of cancer immunotherapy in patients (52). Moreover, the abnormal expression of APOE in lung, colorectal and gastric cancer has been reported (53)(54)(55)(56); however, the association between APOE and PTC has not been investigated and should be the basis of future research.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis of the association between apolipoprotein E expression and patient prognosis in papillary thyroid carcinoma

et al. 2020

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The prognosis of most patients with papillary thyroid carcinoma (PTC) is excellent despite some cases of tumor progression or relapse. The present study was designed to reveal possible prognostic risk indicators for PTC. Differentially expressed genes (DEGs) extracted from 4 Gene Expression Omnibus (GEO) cohorts were subjected to functional enrichment analyses by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. A dataset from The Cancer Genome Atlas (TCGA) was obtained to filter and validate significant genes using cytoHubba, followed by analysis of their association with clinicopathological characteristics and prognosis. In total, 240 DEGs were identified after data preprocessing. These DEGs were enriched in 'intracellular redox equilibrium', 'release of exosome', 'cell adhesion', 'regulation of extracellular matrix', 'collagen binding' and 'energy metabolism' based on GO analysis which including cellular component, molecular function and biological process. KEGG pathway analysis revealed that the DEGs were enriched in thyroid hormone synthesis, pathways in cancer, focal adhesion, metabolic pathways, apoptosis, PPAR signaling pathway and PI3K/AKT signaling pathway. Using cytoHubba, the following hub genes were identified: Apolipoprotein E (APOE); hemoglobin subunit α1 (HBA1); angiotensin II receptor 1 (AGTR1); collagen I α1 (COL1A1); galectin 3 (LGALS3) and TIMP metallopeptidase inhibitor 1 (TIMP1). The expression of these genes was found to be consistent in TCGA datasets. Kaplan-Meier analysis revealed that APOE was significantly associated with overall survival (P=0.00067) and disease free survival (P=0.00220). Additionally, low expression of APOE was significantly associated with older age (P<0.001) and higher TNM stage (P<0.001) compared with the high expression group. Therefore, APOE may function as a predictive risk indicator for progression as well as prognosis of PTC.

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Secretomes are a potential source of molecular targets for cancer therapies and indicate that APOE is a candidate biomarker for lung adenocarcinoma metastasis

Cited by 14 publications

References 37 publications

Proteomic profiling of human plasma identifies apolipoprotein E as being associated with smoking and a marker for squamous metaplasia of the lung

Proteomic profiling of human plasma identifies apolipoprotein E as being associated with smoking and a marker for squamous metaplasia of the lung

Altered Immune-Related Gene Expressions Indicate Oral Cancer Nodal Disease

Integrated bioinformatics analysis of the association between apolipoprotein E expression and patient prognosis in papillary thyroid carcinoma

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