Prediction of outcome of advanced cervical cancer to thermoradiotherapy according to expression profiles of 35 genes selected by cDNA microarray analysis

Hirabayashi, Yoko; Togashi, Akira; Horikoshi, Kenichi; Imamura, Masahiro; Sougawa, Mitsuharu; Sawada, Satoshi; Tsunoda, Tatsuhiko; Nakamura, Yusuke; Katagiri, Toyomasa

doi:10.1016/j.ijrobp.2004.02.047

Cited by 65 publications

(40 citation statements)

References 42 publications

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“…One concerning aspect of the literature is that different studies report different sets of potentially prognosticating genes, with little overlap among these reports (7,8). There are many reasons for this variation, but one possibility that has been understudied is the issue of gene expression heterogeneity within patients' tumors.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling in Cervical Cancer: An Exploration of Intratumor Heterogeneity

Bachtiary

Boutros

Pintilie³

et al. 2006

Clinical Cancer Research

125

111

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Purpose: To explore intratumor heterogeneity in gene expression profiles from patients with cervical cancer. Experimental Design: A total of 33 biopsies were obtained from 11patients, sampling between two and five different areas for each tumor.The extracted RNA was hybridized onto theAffymetrix U133 Plus 2.0 oligonucleotide chip. The variance of expression within a patient (W), between patients (B) and the total variance (T = W + B) were calculated for each ProbeSet, and the ratio W/T was used as a measure of intratumor heterogeneity. Gene Ontology functional analysis was done to assess the function of genes that had high W/T (top 10%) and low W/T (bottom 10%) values.Results: In total, 448 ProbeSets (2.2% of the total) had W/T < 0.10, indicating low intratumor heterogeneity, and 537 ProbeSets (2.7% of the total) had W/T > 0.90, indicating high intratumor heterogeneity. In total 14,473 ProbeSets (72.4%) had higher intertumor than intratumor heterogeneity (W/T < 0.5). Genes with low intratumor heterogeneity were characterized by a statistically significant enrichment of immune-related functions (P < 0.0001). Genes with high intratumor heterogeneity were characterized by a significant tendency towards nuclear localization and nucleic acid binding (both P < 0.0001). For genes with W/T > 0.5, more than six biopsies would be required to minimize the intratumoral heterogeneity to <0.15; if W/T is 0.3 to 0.4, four biopsies are required; and for low W/T of 0.16 to 0.3, only two to three biopsies would be needed. Conclusion: Although the intratumor heterogeneity was low for the majority of the tested ProbeSets, for many genes, multiple biopsies are required to obtain a reliable estimate of gene expression.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling in Cervical Cancer: An Exploration of Intratumor Heterogeneity

Bachtiary

Boutros

Pintilie³

et al. 2006

Clinical Cancer Research

125

111

View full text Add to dashboard Cite

show abstract

“…Overall, the expression of these enzymes correlates with tumor aggressiveness (Westermarck and Kahari, 1999;Jones et al, 2004). Despite several studies of BI-1 in cancer (Grzmil et al, 2003(Grzmil et al, , 2006Harima et al, 2004), its role is still unclear. In breast cancer cells, BI-1 levels are regulated by tamoxifen (Del Carmen et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

BAX inhibitor-1 enhances cancer metastasis by altering glucose metabolism and activating the sodium-hydrogen exchanger: the alteration of mitochondrial function

Shin

et al. 2010

Oncogene

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The anti-apoptotic protein, BAX inhibitor-1 (BI-1), has a role in cancer/tumor progression. BI-1-overexpressing HT1080 and B16F10 cells produced higher lung weights and tumor volumes after injection into the tail veins of mice. Transfection of BI-1 siRNA into cells before injection blocked lung metastasis. in vitro, the overexpression of BI-1 increased cell mobility and invasiveness, with highly increased glucose consumption and cytosolic accumulation of lactate and pyruvate, but decreased mitochondrial O 2 consumption and ATP production. Glucose metabolism-associated extracellular pH also decreased as cells excreted more H þ , and sodium hydrogen exchanger (NHE) activity increased, probably as a homeostatic mechanism for intracellular pH. These alterations activated MMP 2/9 and cell mobility and invasiveness, which were reversed by the NHE inhibitor, 5-(N-ethyl-N-isopropyl) amiloride (EIPA), suggesting a role for NHE in cancer metastasis. In both in vitro and in vivo experiments, C-terminal deleted (CDBI-1) cells showed similar results to control cells, suggesting that the C-terminal motif is required for BI-1-associated alterations of glucose metabolism, NHE activation and cancer metastasis. These findings strongly suggest that BI-1 reduces extracellular pH and regulates metastasis by altering glucose metabolism and activating NHE, with the C-terminal tail having a pivotal role in these processes.

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“…The Medline database was used by entering all possible combinations from one of the following key words; 'radiosensitivity/radiosensitive/radioresistant/radiation/ radiotherapy,' with 'microarray'. these analyses are uterine cervical cancer (4 studies), head and neck cancer (3 studies), colorectal cancer (2 studies), breast cancer (1 study), esophageal cancer (1 study), pancreatic cancer (1 study), lung cancer (1 study), glioblastoma (1 study), hepatocellular carcinoma (1 study) and choroidal melanoma (1 study) (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, Harima et al identified a set of genes related to thermoradiosensitivity of cervical cancer (14). They compared the expression profiles of 8 thermoradiosensitive and 11 thermoradioresistant tumors obtained by biopsy before treatment using a cDNA microarray consisting of 23,040 genes.…”

Section: Introductionmentioning

confidence: 99%

Predicting the tumor response to radiotherapy using microarray analysis (Review)

Ogawa¹,

Murayama²,

Mori³

2007

Oncol Rep

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Abstract. Predicting the tumor response to radiotherapy is one of the major goals of human cancer treatment. Identification of the genes that are differentially expressed between radiosensitive and radioresistant cancers by global gene analysis may provide new insights into the mechanisms underlying clinical radioresistance and improve the efficacy of radiotherapy. In this study, we reviewed the published reports identifying sets of discriminating genes using microarray analysis that can be used for characterization and the prediction of response to radiotherapy in human cancers. These reports indicate that many of the identified genes were associated with DNA-repair, apoptosis, growth factor, signal transduction, cell cycle and cell adhesion. Several genes were found to be predictors of the radiation response with various cancers and certain sets of identified genes were also found to predict the radiation response by using clustering analysis. Global gene expression profiling of responders and nonresponders can be useful in predicting responses to radiotherapy and may also provide insights into the development of individualized therapies and novel therapeutic targets. Contents1. Introduction 2. Microarray analysis comparing radiosensitive and radioresistant cancer samples and cancer cell lines 3. Summary of the identified genes from cancer cell lines investigated by microarray IntroductionRadiotherapy is one of the major treatments for patients with various cancers. The general rationale for radiotherapy is based on the findings that radiation can inhibit cell proliferation or induce apoptotic cell death in vitro and inhibit tumor growth in vivo (1). However, the tumor response to radiotherapy sometimes differs among individual tumors even with the same histological field, and the lack of knowledge regarding the determinants of response has handicapped the development of predictive assays and the development of novel treatment strategies. Therefore, identification of the determinants of the tumor response to radiation has long been a goal of radiation oncologists and biologists. Recently, an association between radioresistance and the expression of several genes was observed, with candidate genes, such as p53 (2), ras (3), raf-1 (4), bcl-2 (5) and survivin (6). Furthermore, cancer stem cells have emerged as a contributor to radioresistance through the preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity (7). Although such discoveries have helped develop a partial understanding of the molecular mechanisms responsible for cellular radiosensitivity, the entire process remains to be elucidated. The advent of microarray gene expression technology permits simultaneous analysis of the expression levels of thousands of genes (8-10). Therefore, a study on molecular genetic events related to radiosensitivity can be conducted. This research can lead to the identification of gene regulatory pathways that result in the development of resistance to therapeutic procedures. To d...

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Prediction of outcome of advanced cervical cancer to thermoradiotherapy according to expression profiles of 35 genes selected by cDNA microarray analysis

Cited by 65 publications

References 42 publications

Gene Expression Profiling in Cervical Cancer: An Exploration of Intratumor Heterogeneity

Gene Expression Profiling in Cervical Cancer: An Exploration of Intratumor Heterogeneity

BAX inhibitor-1 enhances cancer metastasis by altering glucose metabolism and activating the sodium-hydrogen exchanger: the alteration of mitochondrial function

Predicting the tumor response to radiotherapy using microarray analysis (Review)

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