Tumor profiling of co-regulated receptor tyrosine kinase and chemoresistant genes reveal different targeting options for lung and gastroesophageal cancers

Jianzhong Wu, Shuchun Li, Rong Ma, Ashok Kumar Sharma, Shan Bai, Boying Dun, Haixia Cao, Changwen Jing, Jin-Xiong She, Jifeng Feng

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The expression of a number of genes can influence the response rates to chemotherapy while genes encoding receptor tyrosine kinases (RTKs) determine the response to most targeted cancer therapies currently used in clinics. In this study, we evaluated seven genes known to influence chemotherapeutic response (ERCC1, BRCA1, RRM1, TUBB3, STMN1, TYMS, and TOP2A) and five RTKs (EGFR, ERBB2, PDGFRB, VEGFR1 and VEGFR2) in non-small cell lung cancer (NSCLC) and esophagus cancer (EC) and the data are compared to gastric cancer (GC) data reported previously. We demonstrate significant differences in the expression profiles between different cancer types as well as heterogeneity among patients within the same cancer type. In all three cancer types, five chemoresistant genes (TOP2A, STMN1, TYMS, BRCA1 and RRM1) are coordinately up-regulated in almost all EC, approximately 90% of NSCLC and one third of GC patients. Most EC and nearly half of GC patients have increased expression of the three RTKs critical to angiogenesis (PDGFR, VEGFR1 and VEGFR2), while almost none of the NSCLC patients have elevated expression of angiogenic RTKs. A variable percentage of patients in the three cancer types show upregulation of the EGFR family RTKs, EGFR and/or ERBB2. It is of interest to note that approximately 10% of the NSCLC and GC patients are triple-negative for the chemosensitivity genes, angiogenic and EGFR RTK genes. The results suggest significant gene expression differences between different cancer types as well as heterogeneity within each cancer type and therefore different molecules should be targeted for future drug development and clinical trials.

Original languageEnglish (US)
Pages (from-to)5729-5740
Number of pages12
JournalAmerican Journal of Translational Research
Volume8
Issue number12
StatePublished - Jan 1 2016

Fingerprint

Receptor Protein-Tyrosine Kinases
Tumors
Lung Neoplasms
Genes
Stomach Neoplasms
Esophageal Neoplasms
Non-Small Cell Lung Carcinoma
Neoplasms
Platelet-Derived Growth Factor beta Receptor
Gene encoding
Chemotherapy
erbB-1 Genes
Gene expression
Cells
Up-Regulation
Clinical Trials
Molecules
Gene Expression
Drug Therapy
Pharmaceutical Preparations

Keywords

  • Cancer heterogeneity
  • Chemoresistant genes
  • Co-regulation of gene expression
  • Drug targets
  • Normalization
  • Reference genes

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

Cite this

Tumor profiling of co-regulated receptor tyrosine kinase and chemoresistant genes reveal different targeting options for lung and gastroesophageal cancers. / Wu, Jianzhong; Li, Shuchun; Ma, Rong; Sharma, Ashok Kumar; Bai, Shan; Dun, Boying; Cao, Haixia; Jing, Changwen; She, Jin-Xiong; Feng, Jifeng.

In: American Journal of Translational Research, Vol. 8, No. 12, 01.01.2016, p. 5729-5740.

Research output: Contribution to journalArticle

Wu, Jianzhong ; Li, Shuchun ; Ma, Rong ; Sharma, Ashok Kumar ; Bai, Shan ; Dun, Boying ; Cao, Haixia ; Jing, Changwen ; She, Jin-Xiong ; Feng, Jifeng. / Tumor profiling of co-regulated receptor tyrosine kinase and chemoresistant genes reveal different targeting options for lung and gastroesophageal cancers. In: American Journal of Translational Research. 2016 ; Vol. 8, No. 12. pp. 5729-5740.
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AU - Sharma, Ashok Kumar

AU - Bai, Shan

AU - Dun, Boying

AU - Cao, Haixia

AU - Jing, Changwen

AU - She, Jin-Xiong

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AB - The expression of a number of genes can influence the response rates to chemotherapy while genes encoding receptor tyrosine kinases (RTKs) determine the response to most targeted cancer therapies currently used in clinics. In this study, we evaluated seven genes known to influence chemotherapeutic response (ERCC1, BRCA1, RRM1, TUBB3, STMN1, TYMS, and TOP2A) and five RTKs (EGFR, ERBB2, PDGFRB, VEGFR1 and VEGFR2) in non-small cell lung cancer (NSCLC) and esophagus cancer (EC) and the data are compared to gastric cancer (GC) data reported previously. We demonstrate significant differences in the expression profiles between different cancer types as well as heterogeneity among patients within the same cancer type. In all three cancer types, five chemoresistant genes (TOP2A, STMN1, TYMS, BRCA1 and RRM1) are coordinately up-regulated in almost all EC, approximately 90% of NSCLC and one third of GC patients. Most EC and nearly half of GC patients have increased expression of the three RTKs critical to angiogenesis (PDGFR, VEGFR1 and VEGFR2), while almost none of the NSCLC patients have elevated expression of angiogenic RTKs. A variable percentage of patients in the three cancer types show upregulation of the EGFR family RTKs, EGFR and/or ERBB2. It is of interest to note that approximately 10% of the NSCLC and GC patients are triple-negative for the chemosensitivity genes, angiogenic and EGFR RTK genes. The results suggest significant gene expression differences between different cancer types as well as heterogeneity within each cancer type and therefore different molecules should be targeted for future drug development and clinical trials.

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