Short telomere length in peripheral blood leukocyte predicts poor prognosis and indicates an immunosuppressive phenotype in gastric cancer patients.

Abstract:

:Compelling evidences indicate that relative telomere length (RTL) in peripheral blood leukocytes (PBLs) can predict the clinical outcome of several cancers. However, to date, the prognostic value of leukocyte RTL in gastric cancer (GC) patients has not been explored. In this study, relative telomere length (RTL) in peripheral blood leukocytes (PBLs) was measured using a real-time PCR-based method in a total of 693 GC patients receiving surgical resection. The prognostic value of leukocyte RTL was first explored in the training set (112 patients) using Kaplan-Meier and Cox proportional hazards regression analyses. Then an independent cohort of 581 patients was used as a validation set. To explore potential mechanism, we detected the immunophenotypes of peripheral blood mononuclear cells and plasma concentrations of several cytokines in GC patients. Patients with short RTL showed significantly worse overall survival (OS) and relapse-free survival (RFS) than those with long RTL in all patient sets. Furthermore, leukocyte RTL and TNM stage exhibited a notable joint effect in prognosis prediction. Integration of TNM stage and leukocyte RTL significantly improved the prognosis prediction efficacy for GC. In addition, we found that patients with short RTL had a higher CD4(+) T cell percentage in PBMCs, CD19(+)IL-10(+) Breg percentage in B cells and plasma IL-10 concentration, indicating an enhanced immunosuppressive status with short leukocyte RTL. In conclusion, our study for the first time demonstrates that leukocyte RTL is an independent prognostic marker complementing TNM stage and associated with an immunosuppressive phenotype in the peripheral blood lymphocytes in GC patients.

journal_name

Mol Oncol

journal_title

Molecular oncology

authors

Qu F,Li R,He X,Li Q,Xie S,Gong L,Ji G,Lu J,Bao G

doi

10.1016/j.molonc.2014.11.008

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

727-39

issue

3

eissn

1574-7891

issn

1878-0261

pii

S1574-7891(14)00284-1

journal_volume

9

pub_type

杂志文章
  • Gene expression profiling of single circulating tumor cells in ovarian cancer - Establishment of a multi-marker gene panel.

    abstract::The presence of circulating tumor cells (CTCs) in the blood of ovarian cancer patients was shown to correlate with decreased overall survival, whereby CTCs with epithelial-mesenchymal-transition (EMT) or stem-like traits are supposed to be involved in metastatic progression and recurrence. Thus, investigating the tran...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1016/j.molonc.2016.04.002

    authors: Blassl C,Kuhlmann JD,Webers A,Wimberger P,Fehm T,Neubauer H

    更新日期:2016-08-01 00:00:00

  • Differential expression of miRNAs in pancreatobiliary type of periampullary adenocarcinoma and its associated stroma.

    abstract::Periampullary adenocarcinomas can be of two histological subtypes, intestinal or pancreatobiliary. The latter is more frequent and aggressive, and characterized by a prominent desmoplastic stroma, which is tightly related to the biology of the cancer, including its poor response to chemotherapy. Whereas miRNAs are kno...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1016/j.molonc.2015.10.011

    authors: Sandhu V,Bowitz Lothe IM,Labori KJ,Skrede ML,Hamfjord J,Dalsgaard AM,Buanes T,Dube G,Kale MM,Sawant S,Kulkarni-Kale U,Børresen-Dale AL,Lingjærde OC,Kure EH

    更新日期:2016-02-01 00:00:00

  • Identification of lncRNAs associated with early-stage breast cancer and their prognostic implications.

    abstract::Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long noncoding RNA expression profiles associated ...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12489

    authors: Deva Magendhra Rao AK,Patel K,Korivi Jyothiraj S,Meenakumari B,Sundersingh S,Sridevi V,Rajkumar T,Pandey A,Chatterjee A,Gowda H,Mani S

    更新日期:2019-06-01 00:00:00

  • miR-200c and phospho-AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis.

    abstract::Lung metastasis is the major cause of death in osteosarcoma patients. However, molecular mechanisms underlying this metastasis remain poorly understood. To identify key molecules related with pulmonary metastasis of pediatric osteosarcomas, we analyzed high-throughput miRNA expression in a cohort of 11 primary tumors ...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1016/j.molonc.2016.04.004

    authors: Berlanga P,Muñoz L,Piqueras M,Sirerol JA,Sánchez-Izquierdo MD,Hervás D,Hernández M,Llavador M,Machado I,Llombart-Bosch A,Cañete A,Castel V,Font de Mora J

    更新日期:2016-08-01 00:00:00

  • Angiogenin interacts with the plasminogen activation system at the cell surface of breast cancer cells to regulate plasmin formation and cell migration.

    abstract::Angiogenin (ANG), a 14-kDa pro-angiogenic secreted protein, has been shown to play a role in cell migration and tumor invasion, which involve proteolytic cleavage of plasminogen to generate plasmin. However, the mechanism by which ANG regulates plasmin formation and cell migration was not known. Our studies here detec...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1016/j.molonc.2013.12.017

    authors: Dutta S,Bandyopadhyay C,Bottero V,Veettil MV,Wilson L,Pins MR,Johnson KE,Warshall C,Chandran B

    更新日期:2014-05-01 00:00:00

  • Interaction of transcription factor AP-2 gamma with proto-oncogene PELP1 promotes tumorigenesis by enhancing RET signaling.

    abstract::A significant proportion of estrogen receptor-positive (ER+) breast cancer (BC) initially responds to endocrine therapy but eventually evolves into therapy-resistant BC. Transcription factor AP-2 gamma (TFAP2C) is a known regulator of ER activity, and high expression of TFAP2C is associated with a decreased response t...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12871

    authors: Liu J,Liu Z,Li M,Tang W,Pratap UP,Luo Y,Altwegg KA,Li X,Zou Y,Zhu H,Sareddy GR,Viswanadhapalli S,Vadlamudi RK

    更新日期:2020-12-02 00:00:00

  • Adipose tissue from metabolic syndrome mice induces an aberrant miRNA signature highly relevant in prostate cancer development.

    abstract::Prostate cancer (PCa) remains an important public health concern in Western countries. Metabolic syndrome (MeS) is a cluster of pathophysiological disorders with increasing prevalence in the general population that is a risk factor for PCa. Several studies have determined that a crosstalk between white adipose tissue ...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12788

    authors: Massillo C,Duca RB,Lacunza E,Dalton GN,Farré PL,Taha N,Piccioni F,Scalise GD,Gardner K,De Siervi A

    更新日期:2020-09-02 00:00:00

  • Targeted serum miRNA (TSmiR) test for diagnosis and follow-up of (testicular) germ cell cancer patients: a proof of principle.

    abstract::Germ cell cancers (GCC) are the most frequent malignancy in young Caucasian males. GCC can consist of seminomas (SE) and non-seminomas (malignant NS: embryonal carcinoma (EC), yolk sac tumor (YS), choriocarcinoma (CH) and teratoma (TE)). Current serum-markers used for diagnosis and follow-up (AFP, hCG) are predominant...

    journal_title:Molecular oncology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1016/j.molonc.2013.08.002

    authors: Gillis AJ,Rijlaarsdam MA,Eini R,Dorssers LC,Biermann K,Murray MJ,Nicholson JC,Coleman N,Dieckmann KP,Belge G,Bullerdiek J,Xu T,Bernard N,Looijenga LH

    更新日期:2013-12-01 00:00:00

  • Cigarette smoke enhances oncogene addiction to c-MET and desensitizes EGFR-expressing non-small cell lung cancer to EGFR TKIs.

    abstract::Cigarette smoking is one of the leading risks for lung cancer and is associated with the insensitivity of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it remains undetermined whether and how cigarette smoke affects the therapeutic efficacy of...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12193

    authors: Tu CY,Cheng FJ,Chen CM,Wang SL,Hsiao YC,Chen CH,Hsia TC,He YH,Wang BW,Hsieh IS,Yeh YL,Tang CH,Chen YJ,Huang WC

    更新日期:2018-05-01 00:00:00

  • Multidimensionality of microarrays: statistical challenges and (im)possible solutions.

    abstract::A typical array experiment yields at least tens of thousands of measurements on often not more than a hundred patients, a situation often denoted as the curse of dimensionality. With a focus on prognostic multi-biomarker scores derived from microarrays, we highlight the multidimensionality of the problem and the issue...

    journal_title:Molecular oncology

    pub_type: 杂志文章,评审

    doi:10.1016/j.molonc.2011.01.002

    authors: Michiels S,Kramar A,Koscielny S

    更新日期:2011-04-01 00:00:00

  • Intratumor heterogeneity defines treatment-resistant HER2+ breast tumors.

    abstract::Targeted therapy for patients with HER2-positive (HER2+) breast cancer has improved overall survival, but many patients still suffer relapse and death from the disease. Intratumor heterogeneity of both estrogen receptor (ER) and HER2 expression has been proposed to play a key role in treatment failure, but little work...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12375

    authors: Rye IH,Trinh A,Saetersdal AB,Nebdal D,Lingjaerde OC,Almendro V,Polyak K,Børresen-Dale AL,Helland Å,Markowetz F,Russnes HG

    更新日期:2018-11-01 00:00:00

  • Theranostic applications of antibodies in oncology.

    abstract::Targeted therapies, including antibodies, are becoming increasingly important in cancer therapy. Important limitations, however, are that not every patient benefits from a specific antibody therapy and that responses could be short-lived due to acquired resistance. In addition, targeted therapies are quite expensive a...

    journal_title:Molecular oncology

    pub_type: 杂志文章,评审

    doi:10.1016/j.molonc.2014.03.010

    authors: Fleuren ED,Versleijen-Jonkers YM,Heskamp S,van Herpen CM,Oyen WJ,van der Graaf WT,Boerman OC

    更新日期:2014-06-01 00:00:00

  • Gene regulatory networking reveals the molecular cue to lysophosphatidic acid-induced metabolic adaptations in ovarian cancer cells.

    abstract::Extravasation and metastatic progression are two main reasons for the high mortality rate associated with cancer. The metastatic potential of cancer cells depends on a plethora of metabolic challenges prevailing within the tumor microenvironment. To achieve higher rates of proliferation, cancer cells reprogram their m...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12046

    authors: Ray U,Roy Chowdhury S,Vasudevan M,Bankar K,Roychoudhury S,Roy SS

    更新日期:2017-05-01 00:00:00

  • Combination therapy targeting the elevated interleukin-6 level reduces invasive migration of BRAF inhibitor-resistant melanoma cells.

    abstract::The identification of novel antimetastatic therapeutic targets is necessary for improved treatment of patients with acquired BRAF inhibitor-resistant (BRAFi-R) melanoma, in whom metastasis is a major concern. Our present study focused on the identification of such targets to explore novel antimetastatic therapeutic op...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12433

    authors: Mohapatra P,Prasad CP,Andersson T

    更新日期:2019-02-01 00:00:00

  • Germline pharmacogenomics in oncology: decoding the patient for targeting therapy.

    abstract::Pharmacogenomics is the study of genetic factors determining drug response or toxicity. The use of pharmacogenomics is especially desirable in oncology because the therapeutic index of oncology drugs is often narrow, the need for favorable drug response is often acute, and the consequences of drug toxicity can be life...

    journal_title:Molecular oncology

    pub_type: 杂志文章,评审

    doi:10.1016/j.molonc.2012.01.005

    authors: O'Donnell PH,Ratain MJ

    更新日期:2012-04-01 00:00:00

  • Pharmacologically enhanced expression of GPNMB increases the sensitivity of melanoma cells to the CR011-vcMMAE antibody-drug conjugate.

    abstract::GPNMB is a melanoma-associated glycoprotein that is targeted by the CR011-vcMMAE antibody-drug conjugate (ADC). Previous studies have shown that CR011-vcMMAE induces the apoptosis of GPNMB-expressing tumor cells in vitro and tumor regression in xenograft models. This ADC is currently in clinical trials for melanoma. I...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1016/j.molonc.2008.02.002

    authors: Qian X,Mills E,Torgov M,LaRochelle WJ,Jeffers M

    更新日期:2008-06-01 00:00:00

  • The brain acid-soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin.

    abstract::The MYC protein is a transcription factor with oncogenic potential controlling fundamental cellular processes such as cell proliferation, metabolism, differentiation, and apoptosis. The MYC gene is a major cancer driver, and elevated MYC protein levels are a hallmark of most human cancers. We have previously shown tha...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12636

    authors: Hartl M,Puglisi K,Nist A,Raffeiner P,Bister K

    更新日期:2020-03-01 00:00:00

  • Genomic profiling of newly diagnosed glioblastoma patients and its potential for clinical utility - a prospective, translational study.

    abstract::Glioblastoma (GBM) is an incurable brain tumor for which new treatment strategies are urgently needed. Next-generation sequencing of GBM has most often been performed retrospectively and on archival tissue from both diagnostic and relapse surgeries with limited knowledge of clinical information, including treatment gi...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12790

    authors: Nørøxe DS,Yde CW,Østrup O,Michaelsen SR,Schmidt AY,Kinalis S,Torp MH,Skjøth-Rasmussen J,Brennum J,Hamerlik P,Poulsen HS,Nielsen FC,Lassen U

    更新日期:2020-09-04 00:00:00

  • MiR-195 and miR-497 suppress tumorigenesis in lung cancer by inhibiting SMURF2-induced TGF-β receptor I ubiquitination.

    abstract::SMURF2 is a member of the HECT family of E3 ubiquitin ligases that have important roles as a negative regulator of transforming growth factor-β (TGF-β) signaling through ubiquitin-mediated degradation of TGF-β receptor I. However, the regulatory mechanism of SMURF2 is largely unknown. In this study, we identified that...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12581

    authors: Chae DK,Park J,Cho M,Ban E,Jang M,Yoo YS,Kim EE,Baik JH,Song EJ

    更新日期:2019-12-01 00:00:00

  • Recurrence-associated gene signature optimizes recurrence-free survival prediction of colorectal cancer.

    abstract::High throughput gene expression profiling has showed great promise in providing insight into molecular mechanisms. Metastasis-related mRNAs may potentially enrich genes with the ability to predict cancer recurrence, therefore we attempted to build a recurrence-associated gene signature to improve prognostic prediction...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12117

    authors: Tian X,Zhu X,Yan T,Yu C,Shen C,Hu Y,Hong J,Chen H,Fang JY

    更新日期:2017-11-01 00:00:00

  • Circulating tumor cell detection and single-cell analysis using an integrated workflow based on ChimeraX® -i120 Platform: A prospective study.

    abstract::Circulating tumor cell (CTC) analysis holds great potential to be a noninvasive solution for clinical cancer management. A complete workflow that combined CTC detection and single-cell molecular analysis is required. We developed the ChimeraX® -i120 platform to facilitate negative enrichment, immunofluorescent labelin...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12876

    authors: Wang PX,Sun YF,Jin WX,Cheng JW,Peng HX,Xu Y,Zhou KQ,Chen LM,Huang K,Wu SY,Hu B,Zhang ZF,Guo W,Cao Y,Zhou J,Fan J,Yang XR

    更新日期:2020-12-10 00:00:00

  • Inhibition of fucosylation in human invasive ductal carcinoma reduces E-selectin ligand expression, cell proliferation, and ERK1/2 and p38 MAPK activation.

    abstract::Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLeX/A ), and α-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12163

    authors: Carrascal MA,Silva M,Ramalho JS,Pen C,Martins M,Pascoal C,Amaral C,Serrano I,Oliveira MJ,Sackstein R,Videira PA

    更新日期:2018-05-01 00:00:00

  • Prioritization of candidate cancer drugs based on a drug functional similarity network constructed by integrating pathway activities and drug activities.

    abstract::Due to the speed, efficiency, relative risk, and lower costs compared to traditional drug discovery, the prioritization of candidate drugs for repurposing against cancers of interest has attracted the attention of experts in recent years. Herein, we present a powerful computational approach, termed prioritization of c...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12564

    authors: Di J,Zheng B,Kong Q,Jiang Y,Liu S,Yang Y,Han X,Sheng Y,Zhang Y,Cheng L,Han J

    更新日期:2019-10-01 00:00:00

  • Pharmacologic inhibition of Akt in combination with chemotherapeutic agents effectively induces apoptosis in ovarian and endometrial cancer cell lines.

    abstract::The PI3K/Akt signaling pathway, the most frequently altered signaling system in human cancer, is a crucial inducer of dysregulated proliferation and neoplastic processes; however, few therapeutic strategies using PI3K/Akt inhibitors singly have been shown to be effective. The purpose of this paper was to underline the...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12888

    authors: Fabi F,Adam P,Parent S,Tardif L,Cadrin M,Asselin E

    更新日期:2020-12-18 00:00:00

  • Role of ultraviolet mutational signature versus tumor mutation burden in predicting response to immunotherapy.

    abstract::Hydrophobic neoantigens are more immunogenic because they are better presented by the major histocompatibility complex and better recognized by T cells. Tumor cells can evade the immune response by expressing checkpoints such as programmed death ligand 1. Checkpoint blockade reactivates immune recognition and can be e...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12748

    authors: Pham TV,Boichard A,Goodman A,Riviere P,Yeerna H,Tamayo P,Kurzrock R

    更新日期:2020-08-01 00:00:00

  • NFIB is a potential target for estrogen receptor-negative breast cancers.

    abstract:BACKGROUND:The association between nuclear factor I/B (NFIB) gene and triple negative breast cancer has been previously suggested. METHODS:We investigated the relationship between NFIB mRNA and protein expression and molecular subtypes of breast cancer as well as the effect of NFIB silencing on the proliferation and a...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1016/j.molonc.2011.08.002

    authors: Moon HG,Hwang KT,Kim JA,Kim HS,Lee MJ,Jung EM,Ko E,Han W,Noh DY

    更新日期:2011-12-01 00:00:00

  • Mining cancer gene expression databases for latent information on intronic microRNAs.

    abstract::Around 50% of all human microRNAs reside within introns of coding genes and are usually co-transcribed. Gene expression datasets, therefore, should contain a wealth of miRNA-relevant latent information, exploitable for many basic and translational research aims. The present study was undertaken to investigate this pos...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1016/j.molonc.2014.10.001

    authors: Monterisi S,D'Ario G,Dama E,Rotmensz N,Confalonieri S,Tordonato C,Troglio F,Bertalot G,Maisonneuve P,Viale G,Nicassio F,Vecchi M,Di Fiore PP,Bianchi F

    更新日期:2015-02-01 00:00:00

  • TR1801-ADC: a highly potent cMet antibody-drug conjugate with high activity in patient-derived xenograft models of solid tumors.

    abstract::cMet is a well-characterized oncogene that is the target of many drugs including small molecule and biologic pathway inhibitors, and, more recently, antibody-drug conjugates (ADCs). However, the clinical benefit from cMet-targeted therapy has been limited. We developed a novel cMet-targeted 'third-generation' ADC, TR1...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12600

    authors: Gymnopoulos M,Betancourt O,Blot V,Fujita R,Galvan D,Lieuw V,Nguyen S,Snedden J,Stewart C,Villicana J,Wojciak J,Wong E,Pardo R,Patel N,D'Hooge F,Vijayakrishnan B,Barry C,Hartley JA,Howard PW,Newman R,Coronella J

    更新日期:2020-01-01 00:00:00

  • Post-transcriptional regulation of PIAS3 expression by miR-18a in malignant mesothelioma.

    abstract::Protein inhibitor of activated STAT3 (PIAS3) is an endogenous suppressor of signal transducer and activator of transcription 3 (STAT3) signaling. By directly interacting with phosphorylated STAT3, PIAS3 can block the downstream transcriptional activity of STAT3, which is hyper-activated in various cancers. We previous...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1002/1878-0261.12386

    authors: He T,McColl K,Sakre N,Chen Y,Wildey G,Dowlati A

    更新日期:2018-12-01 00:00:00

  • Inhibition of doxorubicin-induced HER3-PI3K-AKT signalling enhances apoptosis of ovarian cancer cells.

    abstract::Resistance to chemotherapy is a serious problem for the successful treatment of ovarian cancer patients but signalling pathways that contribute to this chemoinsensitivity are largely unknown. We demonstrate that the chemotherapeutic drug doxorubicin induces activation of the HER3-PI3K-AKT signalling cascade in ovarian...

    journal_title:Molecular oncology

    pub_type: 杂志文章

    doi:10.1016/j.molonc.2012.07.001

    authors: Bezler M,Hengstler JG,Ullrich A

    更新日期:2012-10-01 00:00:00