Changes in gene expression induced by chemoradiation in advanced cervical carcinoma: A microarray study of RTOG C-0128

Zempolich, Karen; Fuhrman, C.; Milash, Brett; Flinner, R.; Greven, Kathryn M.; Ryu, Janice; Forbes, Alastair; Kerlin, K.; Nichols, R.C.; Gaffney, David K.

doi:10.1016/j.ygyno.2008.01.027

Cited by 15 publications

(10 citation statements)

References 13 publications

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“…Elevated levels of RAD51 have been associated with increased invasiveness in breast cancer patients [37] and have been demonstrated to be an independent prognostic marker of survival in non-small cell lung cancer patients [38]. A previous microarray study of paired cervical tumor samples (pre- and post-chemoradiotherapy) reported down-regulation of RAD51 after treatment [5], supporting the hypothesis that radiation sensitivity is facilitated by a diminished DNA repair response. Targeting strategies against this gene have been developed as possible anticancer treatments; attempts to inhibit RAD51 have proven to be successful in reducing treatment resistance in tumor cells [39,40].…”

Section: Discussionmentioning

confidence: 89%

“…Gene expression studies have been conducted across many tumor types to investigate the patterns of genes involved in intrinsic resistance. In cervical cancer, relatively few studies have been focused on identifying baseline resistance to chemoradiotherapy [5-7]. Therefore, the aim of our study was to investigate the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

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Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure

Bălăcescu

Tudoran

et al. 2014

BMC Cancer

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BackgroundAdvanced squamous cervical cancer, one of the most commonly diagnosed cancers in women, still remains a major problem in oncology due to treatment failure and distant metastasis. Antitumor therapy failure is due to both intrinsic and acquired resistance; intrinsic resistance is often decisive for treatment response. In this study, we investigated the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer.MethodsTwenty-one patients with locally advanced squamous cell carcinoma were enrolled in this study. Primary biopsies harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient’s 6 months clinical response. Ingenuity Pathway Analysis was used to investigate the altered molecular function and canonical pathways between the responding and non-responding patients. The microarray results were validated by qRT-PCR and immunohistochemistry. An additional set of 24 formalin-fixed paraffin-embedded cervical cancer samples was used for independent validation of the proteins of interest.ResultsA 2859-gene signature was identified to distinguish between responder and non-responder patients. ‘DNA Replication, Recombination and Repair’ represented one of the most important mechanisms activated in non-responsive cervical tumors, and the ‘Role of BRCA1 in DNA Damage Response’ was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262). Immunohistological staining confirmed increased expression of BRCA1, BRIP1, FANCD2 and RAD51 in non-responsive compared with responsive advanced squamous cervical cancer, both in the initial set of 21 cervical cancer samples and the second set of 24 samples.ConclusionsOur findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information about the patients at risk for treatment failure.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure

Bălăcescu

Tudoran

et al. 2014

BMC Cancer

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“…The overexpression of CyclinB1 has been found in brain astrocytoma, cervical carcinoma, lung cancer, and many other cancers [14,15]. CCNB1 amplification was also reported in colorectal adenocarcinomas [16].…”

Section: Introductionmentioning

confidence: 99%

Association Study of Germline Variants in CCNB1 and CDK1 with Breast Cancer Susceptibility, Progression, and Survival among Chinese Han Women

Chen

Xie

et al. 2013

PLoS ONE

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The CCNB1 and CDK1 genes encode the proteins of CyclinB1 and CDK1 respectively, which interact with each other and are involved in cell cycle regulation, centrosome duplication and chromosome segregation. This study aimed to investigate whether the genetic variants in these two genes may affect breast cancer (BC) susceptibility, progression, and survival in Chinese Han population using haplotype-based analysis. A total of ten tSNPs spanning from 2kb upstream to 2kb downstream of these genes were genotyped in 1204 cases and 1204 age-matched cancer-free controls. The haplotype blocks were determined according to our genotyping data and linkage disequilibrium (LD) status of these SNPs. For CCNB1, rs2069429 was significantly associated with increased BC susceptibility under recessive model (OR=2.352, 95%CI=1.480-3.737), so was the diplotype TAGT/TAGT (OR=1.947 95%CI=1.154-3.284, P=0.013). In addition, rs164390 was associated with Her2-negative BC. For CDK1, rs2448343 and rs1871446 were significantly associated with decreased BC risk under dominant models, so was the haplotype ATATT. These two SNPs also showed a dose-dependent effect on BC susceptibility. Using stratified association analysis, we found that women with the heterozygotes or minor allele homozygotes of rs2448343 had much less BC susceptibility among women with BMI<23. In CDK1, three closely located SNPs, rs2448343, rs3213048 and rs3213067, were significantly associated with tumor’s PR status: the heterozygotes of rs2448343 were associated with PR-positive tumors, while the minor allele homozygotes of rs3213048 and heterozygotes of rs3213067 were associated with PR-negative BC tumors. In survival analysis, rs1871446 was associated with unfavorable event-free survival under recessive model, so was the CDK1 diplotype ATATG/ATATG, which carried the minor allele homozygote of rs1871446. Our study indicates that genetic polymorphisms of CCNB1 and CDK1 are related to BC susceptibility, progression, and survival in Chinese Han women. Further studies need to be performed in other populations as an independent replication to verify these results.

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“…A study in patients with rectal carcinoma examining the effects of radio-chemotherapy on mRNA levels in normal and malignant tissue showed a differential expression of genes involved in cell adhesion and leukocyte migration [87]. In line with these results, a specific gene cluster, including cell adhesion proteins and molecules involved in apoptosis is upregulated in cervical cancer after chemoradiation, while expression of cell cycle regulators is reduced [88]. Changes in transcription after treatment can also provide information about the therapeutic efficacy of molecular compounds.…”

Section: The Use Of Transcriptomic Data To Clarify Molecular Processementioning

confidence: 88%

Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine

et al. 2016

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New technologies enabling the analysis of various molecules, including DNA, RNA, proteins and small metabolites, can aid in understanding the complex molecular processes in cancer cells. In particular, for the use of novel targeted therapeutics, elucidation of the mechanisms leading to cell death or survival is crucial to eliminate tumor resistance and optimize therapeutic efficacy. While some techniques, such as genomic analysis for identifying specific gene mutations or epigenetic testing of promoter methylation, are already in clinical use, other “omics-based” assays are still evolving. Here, we provide an overview of the current status of molecular profiling methods, including promising research strategies, as well as possible challenges, and their emerging role in radiation oncology.

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Changes in gene expression induced by chemoradiation in advanced cervical carcinoma: A microarray study of RTOG C-0128

Cited by 15 publications

References 13 publications

Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure

Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure

Association Study of Germline Variants in CCNB1 and CDK1 with Breast Cancer Susceptibility, Progression, and Survival among Chinese Han Women

Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine

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