当前位置： SCI文献检索 > Molecular Oncology期刊下所有文献 > Role of ultraviolet mutational signature versus tumor mutation burden in predicting response to immunotherapy.

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 effective in diseases such as melanoma, which harbors a high tumor mutational burden (TMB). Cancers presenting low or intermediate TMB can also respond to checkpoint blockade, albeit less frequently, suggesting the need for biological markers predicting response. We calculated the hydrophobicity of neopeptides produced by probabilistic in silico simulation of the genomic UV exposure mutational signature. We also computed the hydrophobicity of potential neopeptides and extent of UV exposure based on the UV mutational signature enrichment (UVMSE) score in The Cancer Genome Atlas (TCGA; N = 3543 tumors), and in our cohort of 151 immunotherapy-treated patients. In silico simulation showed that UV exposure significantly increased hydrophobicity of neopeptides, especially over multiple mutagenic cycles. There was also a strong correlation (R2  = 0.953) between weighted UVMSE and hydrophobicity of neopeptides in TCGA melanoma patients. Importantly, UVMSE was able to predict better response (P = 0.0026), progression-free survival (P = 0.036), and overall survival (P = 0.052) after immunotherapy in patients with low/intermediate TMB, but not in patients with high TMB. We show that higher UVMSE scores could be a useful predictor of better immunotherapy outcome, especially in patients with low/intermediate TMB, likely due to increased hydrophobicity (and hence immunogenicity) of neopeptides.

journal_name

Mol Oncol

journal_title

Molecular oncology

authors

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

doi

10.1002/1878-0261.12748

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

1680-1694

issue

8

eissn

1574-7891

issn

1878-0261

journal_volume

14

pub_type

杂志文章

相关文献

Molecular Oncology文献大全
  • 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

  • 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

  • DNA polymerase β deficiency is linked to aggressive breast cancer: a comprehensive analysis of gene copy number, mRNA and protein expression in multiple cohorts.

    abstract：:Short arm of chromosome 8 is a hot spot for chromosomal breaks, losses and amplifications in breast cancer. Although such genetic changes may have phenotypic consequences, the identity of candidate gene(s) remains to be clearly defined. Pol β gene is localized to chromosome 8p12-p11 and encodes a key DNA base excision...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1016/j.molonc.2014.01.001

    authors： Abdel-Fatah TM,Russell R,Agarwal D,Moseley P,Abayomi MA,Perry C,Albarakati N,Ball G,Chan S,Caldas C,Ellis IO,Madhusudan S

    更新日期：2014-05-01 00:00:00

  • CPSF4 activates telomerase reverse transcriptase and predicts poor prognosis in human lung adenocarcinomas.

    abstract：:The elevated expression and activation of human telomerase reverse transcriptase (hTERT) is associated with the unlimited proliferation of cancer cells. However, the excise mechanism of hTERT regulation during carcinogenesis is not well understood. In this study, we discovered cleavage and polyadenylation specific fac...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1016/j.molonc.2014.02.001

    authors： Chen W,Qin L,Wang S,Li M,Shi D,Tian Y,Wang J,Fu L,Li Z,Guo W,Yu W,Yuan Y,Kang T,Huang W,Deng W

    更新日期：2014-05-01 00:00:00

  • Next-generation clinical trials: Novel strategies to address the challenge of tumor molecular heterogeneity.

    abstract：:The promise of 'personalized cancer care' with therapies toward specific molecular aberrations has potential to improve outcomes. However, there is recognized heterogeneity within any given tumor-type from patient to patient (inter-patient heterogeneity), and within an individual (intra-patient heterogeneity) as demon...

    journal_title：Molecular oncology

    pub_type： 杂志文章,评审

    doi：10.1016/j.molonc.2014.09.011

    authors： Catenacci DV

    更新日期：2015-05-01 00:00:00

  • Acquired small cell lung cancer resistance to Chk1 inhibitors involves Wee1 up-regulation.

    abstract：:Platinum-based chemotherapy has been the cornerstone treatment for small cell lung cancer (SCLC) for decades, but no major progress has been made in the past 20 years with regard to overcoming chemoresistance. As the cell cycle checkpoint kinase 1 (Chk1) plays a key role in DNA damage response to chemotherapeutic drug...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1002/1878-0261.12882

    authors： Zhao X,Kim IK,Kallakury B,Chahine JJ,Iwama E,Pierobon M,Petricoin E,McCutcheon JN,Zhang YW,Umemura S,Chen V,Wang C,Giaccone G

    更新日期：2020-12-15 00:00:00

  • Genetic susceptibility to breast cancer.

    abstract：:Genetic and lifestyle/environmental factors are implicated in the aetiology of breast cancer. This review summarizes the current state of knowledge on rare high penetrance mutations, as well as moderate and low-penetrance genetic variants implicated in breast cancer aetiology. We summarize recent discoveries from larg...

    journal_title：Molecular oncology

    pub_type： 杂志文章,评审

    doi：10.1016/j.molonc.2010.04.011

    authors： Mavaddat N,Antoniou AC,Easton DF,Garcia-Closas M

    更新日期：2010-06-01 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

  • Prep1 (pKnox1)-deficiency leads to spontaneous tumor development in mice and accelerates EmuMyc lymphomagenesis: a tumor suppressor role for Prep1.

    abstract：:The Prep1 homeodomain transcription factor is essential for embryonic development. 25% of hypomorphic Prep1(i/i) embryos, expressing the gene at 2% of the normal levels, survive pregnancy and live a normal-length life. Later in life, however, these mice develop spontaneous pre-tumoral lesions or solid tumors (lymphoma...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1016/j.molonc.2010.01.001

    authors： Longobardi E,Iotti G,Di Rosa P,Mejetta S,Bianchi F,Fernandez-Diaz LC,Micali N,Nuciforo P,Lenti E,Ponzoni M,Doglioni C,Caniatti M,Di Fiore PP,Blasi F

    更新日期：2010-04-01 00:00:00

  • Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate-induced apoptosis.

    abstract：:Breast cancer (BrCa) metabolism is geared toward biomass synthesis and maintenance of reductive capacity. Changes in glucose and glutamine metabolism in BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa biology remains to be determined. We recently reported that adipocyte coculture alte...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1002/1878-0261.12368

    authors： Balaban S,Lee LS,Varney B,Aishah A,Gao Q,Shearer RF,Saunders DN,Grewal T,Hoy AJ

    更新日期：2018-09-01 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

  • DNA methylation patterns in luminal breast cancers differ from non-luminal subtypes and can identify relapse risk independent of other clinical variables.

    abstract：:The diversity of breast cancers reflects variations in underlying biology and affects the clinical implications for patients. Gene expression studies have identified five major subtypes- Luminal A, Luminal B, basal-like, ErbB2+ and Normal-Like. We set out to determine the role of DNA methylation in subtypes by perform...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1016/j.molonc.2010.11.002

    authors： Kamalakaran S,Varadan V,Giercksky Russnes HE,Levy D,Kendall J,Janevski A,Riggs M,Banerjee N,Synnestvedt M,Schlichting E,Kåresen R,Shama Prasada K,Rotti H,Rao R,Rao L,Eric Tang MH,Satyamoorthy K,Lucito R,Wigler M,Dim

    更新日期：2011-02-01 00:00:00

  • Gene expression profiling of lobular carcinoma in situ reveals candidate precursor genes for invasion.

    abstract：PURPOSE:Lobular carcinoma in situ (LCIS) is both a risk indicator and non-obligate precursor of invasive lobular carcinoma (ILC). We sought to characterize the transcriptomic features of LCIS and ILC, with a focus on the identification of intrinsic molecular subtypes of LCIS and the changes involved in the progression ...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1016/j.molonc.2014.12.005

    authors： Andrade VP,Morrogh M,Qin LX,Olvera N,Giri D,Muhsen S,Sakr RA,Schizas M,Ng CK,Arroyo CD,Brogi E,Viale A,Morrow M,Reis-Filho JS,King TA

    更新日期：2015-04-01 00:00:00

  • Glycan gene expression signatures in normal and malignant breast tissue; possible role in diagnosis and progression.

    abstract：:Glycosylation is the stepwise procedure of covalent attachment of oligosaccharide chains to proteins or lipids, and alterations in this process have been associated with malignant transformation. Simultaneous analysis of the expression of all glycan-related genes clearly gives the advantage of enabling a comprehensive...

    journal_title：Molecular oncology

    pub_type： 杂志文章,评审

    doi：10.1016/j.molonc.2009.12.001

    authors： Potapenko IO,Haakensen VD,Lüders T,Helland A,Bukholm I,Sørlie T,Kristensen VN,Lingjaerde OC,Børresen-Dale AL

    更新日期：2010-04-01 00:00:00

  • Epigenetic alterations involved in cancer stem cell reprogramming.

    abstract：:Current hypotheses suggest that tumors originate from cells that carry out a process of "malignant reprogramming" driven by genetic and epigenetic alterations. Multiples studies reported the existence of stem-cell-like cells that acquire the ability to self-renew and are able to generate the bulk of more differentiate...

    journal_title：Molecular oncology

    pub_type： 杂志文章,评审

    doi：10.1016/j.molonc.2012.10.006

    authors： Muñoz P,Iliou MS,Esteller M

    更新日期：2012-12-01 00:00:00

  • Blood circulating tumor DNA for non-invasive genotyping of colon cancer patients.

    abstract：:Most solid tumors, including colorectal cancers, shed cell-free DNA (ctDNA) in the blood. ctDNA can be analyzed to generate molecular profiles which capture the heterogeneity of the disease more comprehensively then tumor tissue biopsies. This approach commonly called 'liquid biopsy' can be applied to monitor response...

    journal_title：Molecular oncology

    pub_type： 杂志文章,评审

    doi：10.1016/j.molonc.2015.12.005

    authors： Siravegna G,Bardelli A

    更新日期：2016-03-01 00:00:00

  • Targeting breast cancer stem cells.

    abstract：:The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self-renewing cell populations that constitute the bulk of the tumor. Although, the CSC hypothesis does not directly address the cell of origin of cancer, it is...

    journal_title：Molecular oncology

    pub_type： 杂志文章,评审

    doi：10.1016/j.molonc.2010.06.005

    authors： McDermott SP,Wicha MS

    更新日期：2010-10-01 00:00:00

  • Inhibitors of STAT3, β-catenin, and IGF-1R sensitize mouse PIK3CA-mutant breast cancer to PI3K inhibitors.

    abstract：:Although mutations in the phosphoinositide 3-kinase catalytic subunit (PIK3CA) are common in breast cancer, PI3K inhibitors alone have shown modest efficacy. We sought to identify additional pathways altered in PIK3CA-mutant tumors that might be targeted in combination with PI3K inhibitors. We generated two transgenic...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1002/1878-0261.12053

    authors： Merino VF,Cho S,Liang X,Park S,Jin K,Chen Q,Pan D,Zahnow CA,Rein AR,Sukumar S

    更新日期：2017-05-01 00:00:00

  • Exosomal miR-1255b-5p targets human telomerase reverse transcriptase in colorectal cancer cells to suppress epithelial-to-mesenchymal transition.

    abstract：:Cancer cells undergo epithelial-to-mesenchymal transition (EMT) in response to hypoxia. Exosomes produced in tumor microenvironments carry microRNAs (miRNAs) that affect proliferation, metastasis, and EMT. Hypoxic regulation of EMT is associated with telomerase content and stability, but the underlying mechanisms rema...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1002/1878-0261.12765

    authors： Zhang X,Bai J,Yin H,Long L,Zheng Z,Wang Q,Chen F,Yu X,Zhou Y

    更新日期：2020-10-01 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

  • 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

  • miR-634 exhibits anti-tumor activities toward hepatocellular carcinoma via Rab1A and DHX33.

    abstract：:Deregulation of microRNAs contributes to the aberrant growth of hepatocellular carcinoma (HCC). Here, we showed that miR-634 expression was frequently decreased in HCC. Low miR-634 expression was significantly associated with larger tumor size, poorer tumor differentiation, advanced TNM stage, vascular invasion, absen...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1016/j.molonc.2016.09.001

    authors： Zhang CZ,Cao Y,Fu J,Yun JP,Zhang MF

    更新日期：2016-12-01 00:00:00

  • Allo-reactive T cells for the treatment of hematological malignancies.

    abstract：:Several mechanisms can be responsible for control of hematological tumors by allo-reactive T cells. Following allogeneic stem cell transplantation (alloSCT) donor T cells recognizing genetic disparities presented on recipient cells and not on donor cells are main effectors of tumor control, but also of the detrimental...

    journal_title：Molecular oncology

    pub_type： 杂志文章,评审

    doi：10.1016/j.molonc.2015.10.014

    authors： Falkenburg JH,Jedema I

    更新日期：2015-12-01 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

  • 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

  • Functional validation of putative tumor suppressor gene C13ORF18 in cervical cancer by Artificial Transcription Factors.

    abstract：:C13ORF18 is frequently hypermethylated in cervical cancer but not in normal cervix and might serve as a biomarker for the early detection of cervical cancer in scrapings. As hypermethylation is often observed for silenced tumor suppressor genes (TSGs), hypermethylated biomarker genes might exhibit tumor suppressive ac...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1016/j.molonc.2013.02.017

    authors： Huisman C,Wisman GB,Kazemier HG,van Vugt MA,van der Zee AG,Schuuring E,Rots MG

    更新日期：2013-06-01 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

  • ER stress-related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer.

    abstract：:Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of pro...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1002/1878-0261.12365

    authors： Liu CY,Hsu CC,Huang TT,Lee CH,Chen JL,Yang SH,Jiang JK,Chen WS,Lee KD,Teng HW

    更新日期：2018-10-01 00:00:00

  • Excellent translational research in oncology: A journey towards novel and more effective anti-cancer therapies.

    abstract：:Comprehensive Cancer Centres (CCCs) serve as critical drivers for improving cancer survival. In Europe, we have developed an Excellence Designation System (EDS) consisting of criteria to assess "excellence" of CCCs in translational research (bench to bedside and back), with the expectation that many European CCCs will...

    journal_title：Molecular oncology

    pub_type： 杂志文章,评审

    doi：10.1016/j.molonc.2015.12.007

    authors： Rajan A,Berns A,Ringborg U,Celis J,Ponder B,Caldas C,Livingston D,Bristow RG,Hecht TT,Tursz T,van Luenen H,Bono P,Helander T,Seamon K,Smyth JF,Louvard D,Eggermont A,van Harten WH

    更新日期：2016-05-01 00:00:00

  • STAT1 is a sex-specific tumor suppressor in colitis-associated colorectal cancer.

    abstract：:The interferon-inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated sex-specific STAT1 functions in colitis and colitis-associated colorectal cancer (CRC) using mice with specific STAT1 deletion in intestinal epithelial cells (STAT1∆IEC ). Male but not female STAT1∆IEC mi...

    journal_title：Molecular oncology

    pub_type： 杂志文章

    doi：10.1002/1878-0261.12178

    authors： Crnčec I,Modak M,Gordziel C,Svinka J,Scharf I,Moritsch S,Pathria P,Schlederer M,Kenner L,Timelthaler G,Müller M,Strobl B,Casanova E,Bayer E,Mohr T,Stöckl J,Friedrich K,Eferl R

    更新日期：2018-04-01 00:00:00