Exome Sequencing of Oral Squamous Cell Carcinoma Reveals Molecular Subgroups and Novel Therapeutic Opportunities.

Abstract:

:Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic strategies and tailored treatment options is an unmet need. To unveil the mutational spectrum, whole-exome sequencing of 120 OSCC from male individuals in Taiwan was conducted. Analyzing the contributions of the five mutational signatures extracted from the dataset of somatic variations identified four groups of tumors that were significantly associated with demographic and clinical features. In addition, known (TP53, FAT1, EPHA2, CDKN2A, NOTCH1, CASP8, HRAS, RASA1, and PIK3CA) and novel (CHUK and ELAVL1) genes that were significantly and frequently mutated in OSCC were discovered. Further analyses of gene alteration status with clinical parameters revealed that the tumors of the tongue were enriched with copy-number alterations in several gene clusters containing CCND1 and MAP4K2. Through defining the catalog of targetable genomic alterations, 58% of the tumors were found to carry at least one aberrant event potentially targeted by US Food and Drug Administration (FDA)-approved agents. Strikingly, if targeting the p53-cell cycle pathway (TP53 and CCND1) by the drugs studied in phase I-III clinical trials, those possibly actionable tumors are predominantly located in the tongue, suggesting a better prediction of sensitivity to current targeted therapies. Our work revealed molecular OSCC subgroups that reflect etiological and prognostic correlation as well as defined the landscape of major altered events in the coding regions of OSCC genomes. These findings provide clues for the design of clinical trials for targeted therapies and stratification of OSCC patients with differential therapeutic efficacy.

journal_name

Theranostics

journal_title

Theranostics

authors

Su SC,Lin CW,Liu YF,Fan WL,Chen MK,Yu CP,Yang WE,Su CW,Chuang CY,Li WH,Chung WH,Yang SF

doi

10.7150/thno.18551

subject

Has Abstract

pub_date

2017-02-26 00:00:00

pages

1088-1099

issue

5

issn

1838-7640

pii

thnov07p1088

journal_volume

7

pub_type

杂志文章
  • Alginate oligosaccharides improve germ cell development and testicular microenvironment to rescue busulfan disrupted spermatogenesis.

    abstract::Rationale: Busulfan is currently an indispensable anti-cancer drug, particularly for children, but the side effects on male reproduction are so serious that critical drug management is needed to minimize any negative impact. Meanwhile, alginate oligosaccharides (AOS) are natural products with many consequent advantage...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.43189

    authors: Zhao Y,Zhang P,Ge W,Feng Y,Li L,Sun Z,Zhang H,Shen W

    更新日期:2020-02-10 00:00:00

  • Distinct immune signatures in directly treated and distant tumors result from TLR adjuvants and focal ablation.

    abstract::Both adjuvants and focal ablation can alter the local innate immune system and trigger a highly effective systemic response. Our goal is to determine the impact of these treatments on directly treated and distant disease and the mechanisms for the enhanced response obtained by combinatorial treatments. Methods: We com...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.25613

    authors: Chavez M,Silvestrini MT,Ingham ES,Fite BZ,Mahakian LM,Tam SM,Ilovitsh A,Monjazeb AM,Murphy WJ,Hubbard NE,Davis RR,Tepper CG,Borowsky AD,Ferrara KW

    更新日期:2018-06-07 00:00:00

  • Injection of nanoparticles into cloven-hoof animals: Asking for trouble.

    abstract::This article aims at alerting scientists working with nanoparticles or microparticles about the specific adverse reactions due to the intravascular pulmonary macrophages present in pigs and other cloven-hoof animals, but not in humans. The history of a 25-year old study of an ultrasound contrast agent is used to illus...

    journal_title:Theranostics

    pub_type: 评论,杂志文章

    doi:10.7150/thno.22420

    authors: Skotland T

    更新日期:2017-10-23 00:00:00

  • Triple-Modal Imaging of Magnetically-Targeted Nanocapsules in Solid Tumours In Vivo.

    abstract::Triple-modal imaging magnetic nanocapsules, encapsulating hydrophobic superparamagnetic iron oxide nanoparticles, are formulated and used to magnetically target solid tumours after intravenous administration in tumour-bearing mice. The engineered magnetic polymeric nanocapsules m-NCs are ~200 nm in size with negative ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.11918

    authors: Bai J,Wang JT,Rubio N,Protti A,Heidari H,Elgogary R,Southern P,Al-Jamal WT,Sosabowski J,Shah AM,Bals S,Pankhurst QA,Al-Jamal KT

    更新日期:2016-01-01 00:00:00

  • Anti-tumor Efficiency of Lipid-coated Cisplatin Nanoparticles Co-loaded with MicroRNA-375.

    abstract::One of the major challenges in the hepatocellular carcinoma (HCC) treatment is its insensitivity to chemotherapeutic drugs. Here, we report the development of novel lipid-coated cisplatin nanoparticles co-loaded with microRNA-375 (NPC/miR-375) as a potential treatment for chemotherapy insensitive HCC. The NPC/miR-375 ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.13130

    authors: Yang T,Zhao P,Rong Z,Li B,Xue H,You J,He C,Li W,He X,Lee RJ,Ma X,Xiang G

    更新日期:2016-01-01 00:00:00

  • Systemic siRNA Delivery with a Dual pH-Responsive and Tumor-targeted Nanovector for Inhibiting Tumor Growth and Spontaneous Metastasis in Orthotopic Murine Model of Breast Carcinoma.

    abstract::Phenylboronic acid (PBA)-mediated tumor targeting nanovector is an attractive strategy for enhancing siRNA delivery and treatment of metastatic cancers. However, its nonspecific binding with various biological membranes containing cis-diol moieties restricts its potential application by systematic administration. Here...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.16855

    authors: Fan B,Kang L,Chen L,Sun P,Jin M,Wang Q,Bae YH,Huang W,Gao Z

    更新日期:2017-01-01 00:00:00

  • Loss of EGR-1 uncouples compensatory responses of pancreatic β cells.

    abstract::Rationale: Subjects unable to sustain β-cell compensation develop type 2 diabetes. Early growth response-1 protein (EGR-1), implicated in the regulation of cell differentiation, proliferation, and apoptosis, is induced by diverse metabolic challenges, such as glucose or other nutrients. Therefore, we hypothesized that...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.40664

    authors: Leu SY,Kuo LH,Weng WT,Lien IC,Yang CC,Hsieh TT,Cheng YN,Chien PH,Ho LC,Chen SH,Shan YS,Chen YW,Tsai PJ,Sung JM,Tsai YS

    更新日期:2020-03-04 00:00:00

  • Innate immunity derived factors as external modulators of the CXCL12-CXCR4 axis and their role in stem cell homing and mobilization.

    abstract::The α-chemokine CXCL12 (stromal derived factor-1; SDF-1) and its corresponding G(αI) protein-coupled CXCR4 receptor axis play an important role in retention of hematopoietic stem progenitor cells (HSPCs) in bone marrow (BM) stem cell niches. CXCL12 has also been identified as a strong chemoattractant for HSPCs and imp...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.4621

    authors: Ratajczak MZ,Serwin K,Schneider G

    更新日期:2013-01-01 00:00:00

  • Integrating Stimuli-Responsive Properties in Host-Guest Supramolecular Drug Delivery Systems.

    abstract::Host-guest motifs are likely the most recognizable manifestation of supramolecular chemistry. These complexes are characterized by the organization of small molecules on the basis of preferential association of a guest within the portal of a host. In the context of their therapeutic use, the primary application of the...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.31913

    authors: Braegelman AS,Webber MJ

    更新日期:2019-05-15 00:00:00

  • A Combination of DNA-peptide Probes and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS): A Quasi-Targeted Proteomics Approach for Multiplexed MicroRNA Quantification.

    abstract::The distorted and unique expression of microRNAs (miRNAs) in cancer makes them an attractive source of biomarker. There is much evidence indicating that a panel of miRNAs, termed "miRNA fingerprints", is more specific and informative than an individual miRNA as biomarker. Thus, multiplex assays for simultaneous quanti...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.19113

    authors: Xu F,Zhou W,Cao J,Xu Q,Jiang D,Chen Y

    更新日期:2017-07-08 00:00:00

  • Development of Paper-Based Analytical Devices for Minimizing the Viscosity Effect in Human Saliva.

    abstract::Rationale: Saliva as a sample matrix is rapidly gaining interest for disease diagnosis and point-of-care assays because it is easy to collect (non-invasive) and contains many health-related biomarkers. However, saliva poses particular problems relative to more common urine and blood matrices, which includes low analyt...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.24941

    authors: Noiphung J,Nguyen MP,Punyadeera C,Wan Y,Laiwattanapaisal W,Henry CS

    更新日期:2018-06-13 00:00:00

  • Oleic acid-induced NOX4 is dependent on ANGPTL4 expression to promote human colorectal cancer metastasis.

    abstract::Background: Colorectal cancer (CRC) progression and related mortality are highly associated with metabolic disorders. However, the molecular mechanism involved in the regulation of hyperlipidemia-associated CRC metastasis remains unclear. This study aimed to investigate the effects of angiopoietin-like 4 (ANGPTL4) on ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.44744

    authors: Shen CJ,Chang KY,Lin BW,Lin WT,Su CM,Tsai JP,Liao YH,Hung LY,Chang WC,Chen BK

    更新日期:2020-05-30 00:00:00

  • Emerging role of mTOR in tumor immune contexture: Impact on chemokine-related immune cells migration.

    abstract::During the last few decades, cell-based anti-tumor immunotherapy emerged and it has provided us with a large amount of knowledge. Upon chemokines recognition, immune cells undergo rapid trafficking and activation in disease milieu, with immune cells chemotaxis being accompanied by activation of diverse intercellular s...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.45219

    authors: Jin J,Zhao Q

    更新日期:2020-05-15 00:00:00

  • Novel Bioluminescent Activatable Reporter for Src Tyrosine Kinase Activity in Living Mice.

    abstract::Aberrant activation of the Src kinase is implicated in the development of a variety of human malignancies. However, it is almost impossible to monitor Src activity in an in vivo setting with current biochemical techniques. To facilitate the noninvasive investigation of the activity of Src kinase both in vitro and in v...

    journal_title:Theranostics

    pub_type: 杂志文章,收录出版

    doi:10.7150/thno.14306

    authors: Leng W,Li D,Chen L,Xia H,Tang Q,Chen B,Gong Q,Gao F,Bi F

    更新日期:2016-02-24 00:00:00

  • Detection of high-risk atherosclerotic plaques with ultrasound molecular imaging of glycoprotein IIb/IIIa receptor on activated platelets.

    abstract:OBJECTIVE:Ultrasound molecular imaging (UMI) of glycoprotein (GP) IIb/IIIa receptor on activated platelets offers a unique means of identifying high-risk atherosclerosis. We hypothesized that contrast-enhanced ultrasound with microbubbles (MBs) targeted to GP IIb/IIIa could be used to detect and quantify activated plat...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.10020

    authors: Guo S,Shen S,Wang J,Wang H,Li M,Liu Y,Hou F,Liao Y,Bin J

    更新日期:2015-02-05 00:00:00

  • Recent Progress in Light-Triggered Nanotheranostics for Cancer Treatment.

    abstract::Treatments of high specificity are desirable for cancer therapy. Light-triggered nanotheranostics (LTN) mediated cancer therapy could be one such treatment, as they make it possible to visualize and treat the tumor specifically in a light-controlled manner with a single injection. Because of their great potential in c...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.15217

    authors: Zhang P,Hu C,Ran W,Meng J,Yin Q,Li Y

    更新日期:2016-04-27 00:00:00

  • Naphthalene-based fluorescent probes for glutathione and their applications in living cells and patients with sepsis.

    abstract::Rationale: Among the biothiols-related diseases, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and can result in severe oxidative stress and damage to multiple organs. In this study, we aimed to develop a fluorescence chemosensor that can both detect GSH an...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.22252

    authors: Li J,Kwon Y,Chung KS,Lim CS,Lee D,Yue Y,Yoon J,Kim G,Nam SJ,Chung YW,Kim HM,Yin C,Ryu JH,Yoon J

    更新日期:2018-02-03 00:00:00

  • Focused ultrasound activates voltage-gated calcium channels through depolarizing TRPC1 sodium currents in kidney and skeletal muscle.

    abstract::Pulsed focused ultrasound (pFUS) technology is being developed for clinical neuro/immune modulation and regenerative medicine. Biological signal transduction of pFUS forces can require mechanosensitive or voltage-gated plasma membrane ion channels. Previous studies suggested pFUS is capable of activating either channe...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.33876

    authors: Burks SR,Lorsung RM,Nagle ME,Tu TW,Frank JA

    更新日期:2019-07-28 00:00:00

  • MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer.

    abstract::Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of several human cancers, including breast cancer (BC), as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. This review presents the state of the art on the role of miRNAs in the diagnosis, progn...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.11543

    authors: Bertoli G,Cava C,Castiglioni I

    更新日期:2015-07-13 00:00:00

  • Type H blood vessels in bone modeling and remodeling.

    abstract::In the mammalian skeletal system, osteogenesis and angiogenesis are intimately linked during bone growth and regeneration in bone modeling and during bone homeostasis in bone remodeling. Recent studies have expanded our knowledge about the molecular and cellular mechanisms responsible for coupling angiogenesis and bon...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.34126

    authors: Peng Y,Wu S,Li Y,Crane JL

    更新日期:2020-01-01 00:00:00

  • TRPM8-regulated calcium mobilization plays a critical role in synergistic chemosensitization of Borneol on Doxorubicin.

    abstract::Background: Lung cancer has a high mortality rate and is resistant to multiple chemotherapeutics. Natural Borneol (NB) is a monoterpenoid compound that facilitates the bioavailability of drugs. In this study, we investigated the effects of NB on chemosensitivity in the A549 human lung adenocarcinoma cell line and to e...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.45861

    authors: Lai H,Liu C,Hou L,Lin W,Chen T,Hong A

    更新日期:2020-08-13 00:00:00

  • Multivalent Targeting Based Delivery of Therapeutic Peptide using AP1-ELP Carrier for Effective Cancer Therapy.

    abstract::Elastin-like polypeptide (ELP)-based drug delivery has been utilized for various applications including cancer therapies for many years. Genetic incorporation of internalization ligands and cell-targeting peptides along with ELP polymer enhanced tumor accumulation and retention time as well as stability and activities...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.16425

    authors: Sarangthem V,Kim Y,Singh TD,Seo BY,Cheon SH,Lee YJ,Lee BH,Park RW

    更新日期:2016-09-25 00:00:00

  • m6A regulator-based methylation modification patterns characterized by distinct tumor microenvironment immune profiles in colon cancer.

    abstract::Recent studies have highlighted the biological significance of RNA N6-methyladenosine (m6A) modification in tumorigenicity and progression. However, it remains unclear whether m6A modifications also have potential roles in immune regulation and tumor microenvironment (TME) formation. Methods: In this study, we curated...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.52717

    authors: Chong W,Shang L,Liu J,Fang Z,Du F,Wu H,Liu Y,Wang Z,Chen Y,Jia S,Chen L,Li L,Chen H

    更新日期:2021-01-01 00:00:00

  • Functional nanostructures for effective delivery of small interfering RNA therapeutics.

    abstract::Small interfering RNA (siRNA) has proved to be a powerful tool for target-specific gene silencing via RNA interference (RNAi). Its ability to control targeted gene expression gives new hope to gene therapy as a treatment for cancers and genetic diseases. However, siRNA shows poor pharmacological properties, such as lo...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.8491

    authors: Hong CA,Nam YS

    更新日期:2014-09-19 00:00:00

  • 19q13 KRAB zinc-finger protein ZNF471 activates MAPK10/JNK3 signaling but is frequently silenced by promoter CpG methylation in esophageal cancer.

    abstract::Zinc-finger proteins (ZFPs) are the largest transcription factor family in mammals, involved in the regulation of multiple physiologic processes including cell differentiation, proliferation, apoptosis and neoplastic transformation. Approximately one-third of ZFPs are Krüppel-associated box domain (KRAB)-ZFPs. Methods...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.35861

    authors: Sun R,Xiang T,Tang J,Peng W,Luo J,Li L,Qiu Z,Tan Y,Ye L,Zhang M,Ren G,Tao Q

    更新日期:2020-01-12 00:00:00

  • Near-infrared fluorescence imaging in the largely unexplored window of 900-1,000 nm.

    abstract::Near-infrared (NIR) fluorescence imaging has relied on fluorophores that emit in the 700-900 nm NIR-Ia or 1,000-1,700 nm NIR-II window for generating deep-tissue images. Up until now, there have been few fluorophores developed for the 900-1,000 nm NIR-Ib window. This is largely because NIR-Ib light is thought to be st...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.26539

    authors: Deng G,Li S,Sun Z,Li W,Zhou L,Zhang J,Gong P,Cai L

    更新日期:2018-07-16 00:00:00

  • Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma.

    abstract::Salivary adenoid cystic carcinoma (SACC) is a peculiar malignant tumor, characterized by its slow but inexorable growth, with a high incidence of lung metastasis and poor prognosis. Here, we show the upregulated expression of EGFR ligand epiregulin in a subset of SACC cells correlates with lung metastasis and unfavora...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.19712

    authors: Yang WW,Yang LQ,Zhao F,Chen CW,Xu LH,Fu J,Li SL,Ge XY

    更新日期:2017-08-23 00:00:00

  • Dual-Channel Fluorescence Imaging of Hydrogel Degradation and Tissue Regeneration in the Brain.

    abstract::The ability of brain tissue to regenerate is limited; therefore, brain diseases (i.e., trauma, stroke, tumors) often lead to irreversible motor and cognitive impairments. Therapeutic interventions using various types of injectable biomaterials have been investigated to promote endogenous neural differentiation. Despit...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.35606

    authors: Park GK,Kim SH,Kim K,Das P,Kim BG,Kashiwagi S,Choi HS,Hwang NS

    更新日期:2019-05-31 00:00:00

  • Nanotopography-based lymphatic delivery for improved anti-tumor responses to checkpoint blockade immunotherapy.

    abstract::Rationale: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a co-inhibitory checkpoint receptor that is expressed by naïve T-cells in lymph nodes (LNs) to inhibit activation against "self" antigens (Ags). In cancer, anti-CTLA-4 blocks inhibitory action, enabling robust activation of T-cells against tumor Ags pr...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.35280

    authors: Kwon S,Velasquez FC,Rasmussen JC,Greives MR,Turner KD,Morrow JR,Hwu WJ,Ross RF,Zhang S,Sevick-Muraca EM

    更新日期:2019-10-22 00:00:00

  • Smart Sorting of Tumor Phenotype with Versatile Fluorescent Ag Nanoclusters by Sensing Specific Reactive Oxygen Species.

    abstract::Reactive oxygen species (ROS) play a crucial role in cancer formation and development, especially cancer metastasis. However, lack of a precise tool, which could accurately distinguish specific types of ROS, restricts an in-depth study of ROS in cancer development and progression. Herein, we designed smart and versati...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.38422

    authors: Chen X,Wang T,Le W,Huang X,Gao M,Chen Q,Xu S,Yin D,Fu Q,Shao C,Chen B,Shi D

    更新日期:2020-02-10 00:00:00