Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers

Manoj Kumar Kashyap, Arivusudar Marimuthu, Charles Jacob Harrys Kishore, Suraj Peri, Shivakumar Keerthikumar, Thottethodi Subrahmanya Keshava Prasad, Riaz Mahmood, Sudha Rao, Prathibha Ranganathan, Ravinder C. Sanjeeviah, M. Vijayakumar, K. V.Veerendra Kumar, Elizabeth Montgomery, Rekha Vijay Kumar, Akhilesh Pandey

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Cancer of the esophagus is of two main types, each with distinct etiological and pathological characteristics. Esophageal squamous cell carcinoma (ESCC) is predominant type of esophageal cancers worldwide comprising almost 95% of cases. While ESCC is prevalent in the developing world, esophageal adenocarcinoma is commonly seen in the developed country, usually in association with Barrett's esophagus. In spite of its higher prevalence, ESCC has not been studied as intensively as esophageal adenocarcinoma. ESCC and esophageal adenocarcinoma are common cancers worldwide with poor survival rate among patients mainly because both of these cancers lack early biomarkers of identification. Molecular mechanisms contributing to initiation and progression of esophageal squamous cell carcinoma are still poorly understood. Development of DNA microarray technology allows high-throughput identification of gene expression profiles in cancers. In order to identify molecules as candidates for early diagnosis and/or as therapeutic targets, we analyzed the mRNA expression profiles of 20 cases of ESCC using whole genome DNA microarrays. A total of 2,235 genes were differentially regulated in the tumors as compared to the corresponding adjacent normal epithelium of which 881 were significantly upregulated. We validated two molecules that were not previously reported to be overexpressed in ESCC, oral cancer overexpressed 2 (ORAOV2) and fibroblast activation protein (FAP), by immunohistochemical labeling of tissue microarrays and archival tissue sections and found that they were overexpressed in 98% (116/118) and 68% (79/116) of cases, respectively. By gene enrichment analysis, we identified significant downregulation of several genes in the arachidonic acid metabolic pathway. Overall, using this approach we have identified a number of promising novel candidates that can be validated further for their potential to serve as biomarkers for ESCC.

Original languageEnglish (US)
Pages (from-to)34-46
Number of pages13
JournalCancer Biology and Therapy
Volume8
Issue number1
StatePublished - Jan 1 2009
Externally publishedYes

Fingerprint

Tumor Biomarkers
Messenger RNA
Adenocarcinoma
Esophageal Neoplasms
Oligonucleotide Array Sequence Analysis
Neoplasms
Biomarkers
Genes
Barrett Esophagus
Esophageal Squamous Cell Carcinoma
Mouth Neoplasms
Metabolic Networks and Pathways
Transcriptome
Developed Countries
Arachidonic Acid
Early Diagnosis
Down-Regulation
Survival Rate
Epithelium
Fibroblasts

Keywords

  • Biomarkers
  • DNA microarrays
  • Esophageal squamous cell carcinoma
  • Expression profiling
  • Tissue microarrays

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Kashyap, M. K., Marimuthu, A., Kishore, C. J. H., Peri, S., Keerthikumar, S., Prasad, T. S. K., ... Pandey, A. (2009). Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers. Cancer Biology and Therapy, 8(1), 34-46.

Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers. / Kashyap, Manoj Kumar; Marimuthu, Arivusudar; Kishore, Charles Jacob Harrys; Peri, Suraj; Keerthikumar, Shivakumar; Prasad, Thottethodi Subrahmanya Keshava; Mahmood, Riaz; Rao, Sudha; Ranganathan, Prathibha; Sanjeeviah, Ravinder C.; Vijayakumar, M.; Kumar, K. V.Veerendra; Montgomery, Elizabeth; Kumar, Rekha Vijay; Pandey, Akhilesh.

In: Cancer Biology and Therapy, Vol. 8, No. 1, 01.01.2009, p. 34-46.

Research output: Contribution to journalArticle

Kashyap, MK, Marimuthu, A, Kishore, CJH, Peri, S, Keerthikumar, S, Prasad, TSK, Mahmood, R, Rao, S, Ranganathan, P, Sanjeeviah, RC, Vijayakumar, M, Kumar, KVV, Montgomery, E, Kumar, RV & Pandey, A 2009, 'Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers', Cancer Biology and Therapy, vol. 8, no. 1, pp. 34-46.
Kashyap MK, Marimuthu A, Kishore CJH, Peri S, Keerthikumar S, Prasad TSK et al. Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers. Cancer Biology and Therapy. 2009 Jan 1;8(1):34-46.
Kashyap, Manoj Kumar ; Marimuthu, Arivusudar ; Kishore, Charles Jacob Harrys ; Peri, Suraj ; Keerthikumar, Shivakumar ; Prasad, Thottethodi Subrahmanya Keshava ; Mahmood, Riaz ; Rao, Sudha ; Ranganathan, Prathibha ; Sanjeeviah, Ravinder C. ; Vijayakumar, M. ; Kumar, K. V.Veerendra ; Montgomery, Elizabeth ; Kumar, Rekha Vijay ; Pandey, Akhilesh. / Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers. In: Cancer Biology and Therapy. 2009 ; Vol. 8, No. 1. pp. 34-46.
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