高亦博 - Academia.edu (original) (raw)

Papers by 高亦博

Frontiers in Oncology, 2020

Abnormal metabolism is one of the hallmarks of cancer cells. Monoacylglycerol lipase (MGLL), a ke... more Abnormal metabolism is one of the hallmarks of cancer cells. Monoacylglycerol lipase (MGLL), a key enzyme in lipid metabolism, has emerged as an important regulator of tumor progression. In this study, we aimed to characterize the role of MGLL in the development of lung adenocarcinoma (LUAD). To this end, we used tissue microarrays to evaluate the expression of MGLL in LUAD tissue and assessed whether the levels of this protein are correlated with clinicopathological characteristics of LUAD. We found that the expression of MGLL is higher in LUAD samples than that in adjacent non-tumor tissues. In addition, elevated MGLL expression was found to be associated with advanced tumor progression and poor prognosis in LUAD patients. Functional studies further demonstrated that stable short hairpin RNA (shRNA)-mediated knockdown of MGLL inhibits tumor proliferation and metastasis, both in vitro and in vivo, and mechanistically, our data indicate that MGLL regulates Cyclin D1 and Cyclin B1 in...

Nature Communications, 2021

The adenomatous polyposis coli (APC) is a frequently mutated tumour suppressor gene in cancers. H... more The adenomatous polyposis coli (APC) is a frequently mutated tumour suppressor gene in cancers. However, whether APC is regulated at the epitranscriptomic level remains elusive. In this study, we analysed TCGA data and separated 200 paired oesophageal squamous cell carcinoma (ESCC) specimens and their adjacent normal tissues and demonstrated that methyltransferase-like 3 (METTL3) is highly expressed in tumour tissues. m6A-RNA immunoprecipitation sequencing revealed that METTL3 upregulates the m6A modification of APC, which recruits YTHDF for APC mRNA degradation. Reduced APC expression increases the expression of β-catenin and β-catenin-mediated cyclin D1, c-Myc, and PKM2 expression, thereby leading to enhanced aerobic glycolysis, ESCC cell proliferation, and tumour formation in mice. In addition, downregulated APC expression correlates with upregulated METTL3 expression in human ESCC specimens and poor prognosis in ESCC patients. Our findings reveal a mechanism by which the Wnt/β-c...

Frontiers in Molecular Biosciences, 2021

Ferroptosis is a newly discovered type of programmed cell death that differs from canonical apopt... more Ferroptosis is a newly discovered type of programmed cell death that differs from canonical apoptosis. However, the potential role of ferroptosis in lung adenocarcinoma (LUAD) has not been elaborated. In total, 1,328 samples from databases and 36 ferroptosis regulators were included in this study. By combining random survival forest and principal component analysis algorithms, a robust prognostic ferroptosis-related risk score (FRRS) was constructed, and the performance was validated in three independent datasets. Based on the median risk score, two subgroups were identified. Then, comparisons, including of mutational profiles, functional enrichment analyses and immune components, were conducted between subgroups. An immunotherapy cohort was applied to explore potential therapeutic-related biomarkers. Finally, the clinical utility of FRRS was validated in a proteomic cohort. In the TCGA-LUAD cohort, FRRS was calculated using the expression of 11 selected genes, and patients with hig...

Frontiers in Genetics, 2021

For lung adenocarcinoma (LUAD), patients of different stages have strong heterogeneity, and their... more For lung adenocarcinoma (LUAD), patients of different stages have strong heterogeneity, and their overall prognosis varies greatly. Thus, exploration of novel biomarkers to better clarify the characteristics of LUAD is urgent. Multi-omics information of LUAD patients were collected form TCGA. Three independent LUAD cohorts were obtained from gene expression omnibus (GEO). A multi-omics correlation analysis of METTL5 was performed in TCGA dataset. To build a METTL5-associated prognostic score (MAPS). Spathial and random forest methods were first applied for feature selection. Then, LASSO was implemented to develop the model in TCGA cohort. The prognostic value of MAPS was validated in three independent GEO datasets. Finally, functional annotation was conducted using gene set enrichment analysis (GSEA) and the abundances of infiltrated immune cells were estimated by ImmuCellAI algorithm. A total of 901 LUAD patients were included. The expression of METTL5 in LUAD was significantly hig...

Applied Energy, 2020

Abstract Hydrogen production via a two-step thermochemical cycle has attracted considerable resea... more Abstract Hydrogen production via a two-step thermochemical cycle has attracted considerable research interest as it can directly utilize the heat of the high temperature reactor, which eliminates the need for power generation steps and increases energy efficiency, and is understood to be a promising method for producing hydrogen on an industrial scale. The thermochemical cycle uses a metal oxide as a catalyst and involves two steps: thermal reduction and water splitting. The cycle process only requires the input of heat and water to continuously regenerate hydrogen and oxygen, which has almost no impact on the environment and has the potential for sustainable development. Herein we reviewed the two-step thermochemical cycle with regard to reaction heat source, metal oxide characteristics, and chemical reactors. The performance of volatile and non-volatile metal oxides in the cycle reactions has been thoroughly investigated. To date, the most widely studied metal oxides are ZnO/Zn, SnO2/SnO, ceria-based oxides, and iron-based oxides. Among them, doped-ceria and iron-based oxides, which have high redox activities and cycle stabilities, are considered to be the most promising materials. The possibility of achieving large-scale industrial production and the perspective on future material development were also analyzed. It was proved that the poly-cation oxides (PCOs) studied have great potential for hydrolysis, and the use of oxygen transport membrane reactor provides a new perspective for solar hydrogen production.

JAMA Oncology, 2019

IMPORTANCE Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors hav... more IMPORTANCE Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice. OBJECTIVE To evaluate the incidences of treatment-related adverse events of PD-1 and PD-L1 inhibitors and the differences between different drugs and cancer types.

Thoracic Cancer, 2019

Background: Previous research has revealed that Krüppel-like factor 5 (KLF5) may affect DNA damag... more Background: Previous research has revealed that Krüppel-like factor 5 (KLF5) may affect DNA damage repair pathways; however, the associated molecular mechanisms are unclear. Methods: The expression of KLF5 was studied by immunohistochemical staining in paired tumour and normal tissues from 90 patients with ESCC. We studied the effects of KLF5 knockdown on cell proliferation and apoptosis with or without cisplatin treatment in A549 and H1299 cell lines. Moreover, we examined the effect of KLF5 on the DNA damage response. Results: KLF5 was significantly overexpressed in non-small cell lung cancer (NSCLC) tissues, and high KLF5 expression predicted poor prognosis for NSCLC patients. The inhibition of KLF5 markedly augmented cisplatin-induced cell apoptosis. In addition, we observed that KLF5 knockdown could decrease DNA repair potential by inhibiting H2AX S139 phosphorylation in response to cisplatin. Moreover, silencing of KLF5 in NSCLC cell lines inhibited the phosphorylation of checkpoint kinases Chk1 S345 and Chk2 T68. KLF5 knockdown permits cells with broken or damaged DNA strands to enter mitosis by inhibiting the activation of H2AX, Chk1 and Chk2, resulting in mitotic catastrophe. Conclusion: KLF5 plays a significant role in the DNA damage response by regulating DNA damage checkpoint proteins. Inhibition of KLF5 may be a potential therapeutic target for NSCLC patients with cisplatin resistance.

Human pathology, Jan 5, 2018

There is limited evidence regarding the relationship between programmed cell death ligand 1 (PD-L... more There is limited evidence regarding the relationship between programmed cell death ligand 1 (PD-L1) expression on tumor cells (TCs) and prognosis of esophageal squamous cell carcinoma (ESCC). This retrospective study aimed to investigate the clinical significance of PD-L1 expression in ESCC. To assess PD-L1 expression, we conducted immunohistochemistry studies using a tissue microarray encompassing 233 ESCC cases, stage I, II, and III, with detailed clinical data. PD-L1 expression on TCs was observed in 55.4% (129 of 233) of ESCC cases and was not associated with clinicopathological factors. ESCC patients with PD-L1-positive tumors showed significantly better overall survival (OS) and disease-free survival (DFS) than those with PD-L1-negative tumors (P=.023, P=.026, respectively). When patients were stratified into those with stage I-II (127, 54.5%) and stage III (106, 45.5%) disease and those without (134, 57.5%) and with (99, 42.5%) lymph node metastasis, the prognostic effect was...

Oncotarget, Jan 2, 2018

Accumulated evidence has shown that the programmed cell death receptor 1/programmed cell death re... more Accumulated evidence has shown that the programmed cell death receptor 1/programmed cell death receptor 1 ligand 1 (PD-1/PD-L1) pathway is a promising therapeutic target for cancer immunotherapy. However, the association between PD-L1 and esophageal squamous cell carcinoma (ESCC) patient survival remains unclear. We performed a meta-analysis to investigate the prognostic value of PD-L1 in ESCC. We searched PubMed, Embase, Web of Knowledge, and Cochrane Central Register of Controlled Trials databases for relevant studies that evaluated PD-L1 expression and ESCC patient survival. Fixed- and random-effects meta-analyses were conducted according to the heterogeneity of the included studies. Sensitivity analysis was performed according to Metan-based influence analysis. Publication bias was evaluated using Egger's and Begg's tests. Overall, 13 studies with 2,877 patients were included. Twelve studies demonstrated the association between overall survival (OS), and 6 studies descri...

Journal of molecular medicine (Berlin, Germany), Jan 29, 2018

The transforming growth factor β (TGF-β) signaling pathway plays anti- and pro-tumoral roles in t... more The transforming growth factor β (TGF-β) signaling pathway plays anti- and pro-tumoral roles in the vast majority of cancers, and long noncoding RNAs have been reported to play key roles in the highly contextual response process. However, the roles of long noncoding RNAs (lncRNAs) in TGF-β signaling in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we performed RNA-seq to compare lncRNAs expression levels between TGF-β1-treated and untreated ESCC cells and observed that NF-kappaB-interacting lncRNA (NKILA) was remarkably upregulated by the classical TGF-β signaling pathway. RNA profiling of 39 pairs ESCC tumor and adjacent nontumor samples using RT-qPCR demonstrated that NKILA is significantly downregulated in ESCC tumor tissues, and NKILA expression levels were significantly decreased in advanced tumor tissues (III and IV) compared to early stages (I and II) (p < 0.01). Gain- and loss-of-function assays showed that NKILA inhibited ESCC cell metastasis i...

Journal of experimental & clinical cancer research : CR, Jun 23, 2017

Oesophageal cancer is one of the most common malignancies worldwide,and oesophageal squamous cell... more Oesophageal cancer is one of the most common malignancies worldwide,and oesophageal squamous cell carcinoma (ESCC) is the predominant histological type both globally and in China. Collagen triple helix repeat containing 1 (CTHRC1) has been found to be upregulated in ESCC. However, its role in tumourigenesis and progression of ESCC remains unclear. Using our previous ESCC mRNA profiling data, we screened upregulated genes to identify those required for proliferation. Immunohistochemistry was performed to determine the level of CTHRC1 protein expression in 204 ESCC patients. Correlations between CTHRC1 expression and clinicopathological characteristics were assessed. In addition, pyrosequencing and 5-aza-dC treatment were performed to evaluate methylation status of CTHRC1 promoter. In vitro and in vivo analyses were also conducted to determine the role of CTHRC1 in ESCC cell proliferation, migration and invasion, and RNA sequencing and molecular experiments were performed to study the...

Oncotarget, Jan 9, 2016

The LIM-domain protein AJUBA has been reported to be involved in cell-cell adhesion, proliferatio... more The LIM-domain protein AJUBA has been reported to be involved in cell-cell adhesion, proliferation, migration and cell fate decision by acting as a scaffold or adaptor protein. We previously identified AJUBA as a putative cancer gene in esophageal squamous cell carcinoma (ESCC). However, the function and underlying mechanisms of AJUBA in ESCC remain largely unknown. In the present study, we detected AJUBA levels in ESCC tumor tissues and in corresponding adjacent non-tumor tissues by immunohistochemistry (IHC) and investigated the function and mechanism of AJUBA in ESCC cells. The IHC results showed that AJUBA levels were significantly higher in ESCC tissues compared with corresponding adjacent non-tumor tissues (P < 0.001). Both in vitro and in vivo experiments showed that AJUBA promoted cell growth and colony formation, inhibited cisplatin-induced apoptosis of ESCC cells, and promoted ESCC cell migration and invasion. RNA sequencing was used to reveal the oncogenic pathways of ...

Computational and mathematical methods in medicine, 2015

There has been rising interest in the discovery of novel drug indications because of high costs i... more There has been rising interest in the discovery of novel drug indications because of high costs in introducing new drugs. Many computational techniques have been proposed to detect potential drug-disease associations based on the creation of explicit profiles of drugs and diseases, while seldom research takes advantage of the immense accumulation of interaction data. In this work, we propose a matrix factorization model based on known drug-disease associations to predict novel drug indications. In addition, genomic space is also integrated into our framework. The introduction of genomic space, which includes drug-gene interactions, disease-gene interactions, and gene-gene interactions, is aimed at providing molecular biological information for prediction of drug-disease associations. The rationality lies in our belief that association between drug and disease has its evidence in the interactome network of genes. Experiments show that the integration of genomic space is indeed effect...

PloS one, 2015

For a multicomponent therapy, molecular network is essential to uncover its specific mode of acti... more For a multicomponent therapy, molecular network is essential to uncover its specific mode of action from a holistic perspective. The molecular system of a Traditional Chinese Medicine (TCM) formula can be represented by a 2-class heterogeneous network (2-HN), which typically includes chemical similarities, chemical-target interactions and gene interactions. An important premise of uncovering the molecular mechanism is to identify mixed modules from complex chemical-gene heterogeneous network of a TCM formula. We thus proposed a novel method (MixMod) based on mixed modularity to detect accurate mixed modules from 2-HNs. At first, we compared MixMod with Clauset-Newman-Moore algorithm (CNM), Markov Cluster algorithm (MCL), Infomap and Louvain on benchmark 2-HNs with known module structure. Results showed that MixMod was superior to other methods when 2-HNs had promiscuous module structure. Then these methods were tested on a real drug-target network, in which 88 disease clusters were ...

2011 19th International Conference on Geoinformatics, 2011

Evidence-Based Complementary and Alternative Medicine, 2015

In Traditional Chinese Medicine theory, syndrome is essential to diagnose diseases and treat pati... more In Traditional Chinese Medicine theory, syndrome is essential to diagnose diseases and treat patients, and symptom is the foundation of syndrome differentiation. Thus the combination and interaction between symptoms represent the pattern of syndrome at phenotypic level, which can be modeled and analyzed using complex network. At first, we collected inquiry information of 364 depression patients from 2007 to 2009. Next, we learned classification models for 7 syndromes in depression using naïve Bayes, Bayes network, support vector machine (SVM), and C4.5. Among them, SVM achieves the highest accuracies larger than 0.9 except for Yin deficiency. Besides, Bayes network outperforms naïve Bayes for all 7 syndromes. Then key symptoms for each syndrome were selected using Fisher’s score. Based on these key symptoms, symptom networks for 7 syndromes as well as a global network for depression were constructed through weighted mutual information. Finally, we employed permutation test to discov...

IEEE Conference Anthology, 2013

ABSTRACT In Scientific and Technological (S&T) papers, we first define Chinese S&... more ABSTRACT In Scientific and Technological (S&T) papers, we first define Chinese S&T Named Entity (CSTNE) and Relation between Chinese S&T Named Entities (RCSTNE) that can offer help to solve the problem of deep knowledge mining in S&T literature database. Based on the definition of CSTNE and RCSTNE, we build their models which include semantic information. The relevant methods based on knowledge tree are also proposed to identify CSTNE and extract RCSTNE from S&T literatures. The evaluation on a large test set shows good result. Our experiments further demonstrate the practicality of our method.

Journal of natural products, Jan 23, 2015

Esophageal cancer is the eighth most common cancer in the world and ranks as the sixth leading ca... more Esophageal cancer is the eighth most common cancer in the world and ranks as the sixth leading cause of cancer-related mortality. Esophageal cancer has a poor prognosis partially due to its low sensitivity to chemotherapy agents, and the development of new therapeutic agents is urgently needed. Here, the antitumor activity of a natural ent-kaurane diterpenoid, xerophilusin B (1), which was isolated from Isodon xerophilus, a perennial herb frequently used in Chinese folk medicine for tumor treatment, was investigated. Compound 1 exhibited antiproliferative effects against esophageal squamous cell carcinoma (ESCC) cell lines in a time- and dose-dependent manner with lower toxicity against normal human and murine cell lines. In vivo studies demonstrated that 1 inhibited tumor growth of a human esophageal tumor xenograft in BALB/c nude mice without significant secondary adverse effects, indicating its safety in treating ESCC. Furthermore, 1 induced G2/M cell cycle arrest and promoted ap...

ASME 2009 International Manufacturing Science and Engineering Conference, Volume 2, 2009

Picosecond laser ablation of Polydimethylsiloxane (PDMS) has been studied experimentally. The mea... more Picosecond laser ablation of Polydimethylsiloxane (PDMS) has been studied experimentally. The measurements show that laser ablation rate per pulse increases with laser fluence and pulse number. The laser-drilled hole diameter increases with pulse number, and it saturates above certain pulse number for low fluence. The study shows that picosecond laser ablation may provide a good solution for micromachining PDMS, which is more flexible and versatile than the replica molding technique.

Translational Oncology, 2013

The study aims to determine the efficacy and feasibility of a novel folate receptor (FR)-based ci... more The study aims to determine the efficacy and feasibility of a novel folate receptor (FR)-based circulating tumor cell (CTC) detection method in the diagnosis of non-small cell lung cancer (NSCLC). CTCs were collected from 3 ml of blood based on negative enrichment by immunomagnetic beads and then labeled by a conjugate of a tumor-specific ligand folate and an oligonucleotide. After washing off redundant conjugates, the bound conjugates were removed and analyzed by quantitative polymerase chain reaction. The captured cells were validated as tumor cells by immunofluorescence staining. In the evaluation of clinical utility, the results showed that the CTC levels of 153 patients with NSCLC were significantly higher than the controls (49 healthy donors and 64 patients with benign lung diseases; P < .001). With a threshold of 8.64 CTC units, the method showed a sensitivity of 73.2% and a specificity of 84.1% in the diagnosis of NSCLC, especially a sensitivity of 67.2% in stage I disease. Compared with the existing clinical biomarkers such as neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cyfra21-1, and squamous cell carcinoma antigen (SCC Ag), the method showed the highest diagnostic efficiency (area under the curve, 0.823; 95% confidence interval, 0.773-0.874). Together, our results demonstrated that FR-positive CTCs were feasible diagnostic biomarkers in patients with NSCLC, as well as in early-stage tumors.