Downregulation of TS, DPD, ERCC1, GST-Pi, EGFR, and HER2 gene expression after neoadjuvant three-modality treatment in patients with esophageal cancer

Schneider, Sylke; Uchida, Kazumi; Brabender, Jan; Baldus, Stephan; Yochim, JiMin; Danenberg, Kathleen D.; Salonga, Dennis; Chen, Pei; Tsao‐Wei, Denice; Groshen, Susan; Hoelscher, Arnulf H.; Schneider, Paul M.; Danenberg, Peter V.

doi:10.1016/j.jamcollsurg.2004.10.035

Cited by 59 publications

(37 citation statements)

References 21 publications

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“…All primers were selected using the Gene Express software (Applied Biosystems) but were adapted to the needs of RNA/cDNA as extracted out of paraffin-embedded tissue. All primers were validated before use, analogical to the described method of Schneider and others in 2005 (27). All results are expressed as ratios between two absolute measurements (gene of interest/endogenous reference gene) to account for loading differences.…”

Section: Methodsmentioning

confidence: 99%

A Three-Gene Signature for Outcome in Soft Tissue Sarcoma

Hoffmann

Danenberg

Täubert

et al. 2009

Clinical Cancer Research

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Purpose: Finding markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens in soft tissue sarcomas is necessary. In this study, we investigated the prognostic values of hypoxia-inducible factor 1a (HIF1a), heparin-binding epidermal growth factor–like growth factor (HB-EGF), vascular endothelial growth factor (VEGF), and other angiogenesis-related gene expressions, as well as their interrelationships. Experimental Design: Formalin-fixed paraffin-embedded tissue samples were obtained from 45 patients with soft tissue sarcoma (median age 57 years, range 16–85 years). After laser capture microdissection direct quantitative real-time reverse transcription-PCR (TaqMan) assays were done in triplicates to determine HIF1a, HB-EGF, VEGF, and other gene expression levels. Results: Multivariate Cox regression analysis revealed significant independent associations of HB-EGF, HIF1a, and VEGF-C gene expression to the overall survival (P < 0.0001). A combined factor of these three genes showed a relative risk for shorter survival of 5.5, more than twice higher as in an increasing International Union against Cancer Stage. Receiver operating characteristic curve analysis showed a significant sensitivity of 73% and specificity of 82% of this factor for the diagnosis of short (<3 years) versus long (3-9 years) survival (P = 0.0002). VEGF-A showed significant gender differences in the association to survival. Conclusions: Measuring HIF1a, HB-EGF, and VEGF-C expression may contribute to a better understanding of the prognosis of patients with soft tissue sarcoma and may even play a crucial role for the distribution of patients to multimodal therapeutic regimens. Prospective studies investigating the response to different adjuvant or palliative therapies seem to be warranted. (Clin Cancer Res 2009;15(16):5191–8)

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Section: Methodsmentioning

confidence: 99%

A Three-Gene Signature for Outcome in Soft Tissue Sarcoma

Hoffmann

Danenberg

Täubert

et al. 2009

Clinical Cancer Research

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“…DPYD expression has been reported in EAC and correlated with chemoresponse. 33,34 Differential expression of ADH7 [alcohol dehydrogenase 7 (class IV, mu or sigma subunit] was previously identified by a microarray and SAGE (serial analysis of gene expression) study. 35 We confirm here the significant progressive reduction in retinoic acid receptor gamma (RARG) expression 11,31 and highly altered expression of other retinoic acid and retinoid X receptors have been reported.…”

Section: Discussionmentioning

confidence: 99%

Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

Botelho¹,

Schneiders²,

Lord³

et al. 2010

Cancer Biology & Therapy

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“…Primers and probes for ß-actin, VEGF and HIF1a were designed with primer 3 software (Biology Workbench Version 3.2, San Diego Supercomputer Center, at the University of California, San Diego). Primers and probes for TS, DPD, ERCC1 and EGFR were synthesized according to previously published sequences (16). Sequences are shown in Table I.…”

Section: Real-time Quantitative Rt-pcrmentioning

confidence: 99%

Clinical significance of the gene expression profile in residual tumor cells after neoadjuvant chemo-radiotherapy for esophageal cancer

Otake¹,

Mohri²,

Ohi³

et al. 2009

Oncol Rep

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Abstract. Recurrence after neoadjuvant chemoradiotherapy (CRT) followed by surgery is high in patients with esophageal cancer. No standard second line therapy is currently available for patients with recurrence. This study aimed to evaluate the expression of chemo-radiosensitive genes after neoadjuvant CRT in residual tumor cells. Thirteen patients with esophageal squamous cell carcinoma underwent 5-fluorouracil (5-FU) and cisplatin (CDDP) based CRT followed by surgery. Total RNA was successfully obtained from 6 formalin-fixed paraffin-embedded (FFPE) specimens using proteinase K digestion and phenol chloroform extraction. TS and DPD as the 5-FU pathway gene, ERCC1 as the CDDP pathway gene, and EGFR, VEGF, HIF1a as radioresistant genes were measured using real-time reverse transcription polymerase chain reaction; comparing the mRNA level of each gene in pre-CRT biopsy with that in post-CRT FFPE specimens. Five patients had less than one-third residual tumor cells in resected specimens histopathologically; eight had more than twothirds residual tumor cells. There were significant increases in TS (p=0.02) and DPD (p=0.01) levels in residual tumor cells after CRT. Significant decreases in ERCC1 (p=0.03), EGFR (p=0.01), VEGF (p=0.003) and HIF1a (p=0.003) levels were observed. 5-FU and CDDP based CRT up-regulated 5-FU pathway genes and down-regulated CDDP pathway and radioresistant genes. The expression of chemo-radiosensitive genes was significantly changed in residual tumor cells after CRT. Gene expression analysis of residual tumor cells in FFPE specimens may be useful when selecting a second line chemotherapy regimen for recurrent esophageal cancer after CRT.

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Downregulation of TS, DPD, ERCC1, GST-Pi, EGFR, and HER2 gene expression after neoadjuvant three-modality treatment in patients with esophageal cancer

Cited by 59 publications

References 21 publications

A Three-Gene Signature for Outcome in Soft Tissue Sarcoma

A Three-Gene Signature for Outcome in Soft Tissue Sarcoma

Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

Clinical significance of the gene expression profile in residual tumor cells after neoadjuvant chemo-radiotherapy for esophageal cancer

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