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

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.

Role of periostin in esophageal, gastric and colon cancer

“…mRNA profiling of ESCC tissues demonstrated an upregulation of periostin as high as 11-fold (13). Similarly, a quantitative tissue proteomic study reported a 7-fold upregulation of periostin in tumor tissues compared with normal tissues (14). However, a further study investigated whether periostin was secreted by cancer cells or non-epithelial cells, including cancer-associated fibroblasts, and it was observed that it was primarily produced by the latter.…”

Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling

“…The 11q13 amplicon is one of the most frequently amplified chromosomal regions in human cancer and correlates with a poor prognosis (3)(4)(5)(6)(7). Although cyclin D1 (CCND1) has been considered to be the main driver of the 11q13 amplicon (8)(9)(10), it is not sufficient for malignant transformation of normal breast cells and lacks predictive value for the survival of head-and-neck squamous cell carcinoma (HNSCC) or breast cancer patients (8,(11)(12)(13)(14).…”

Functional Swapping between Transmembrane Proteins TMEM16A and TMEM16F

“…For example, genetic mutations in TMEM16C, -16E, -16F, and -16K are associated with craniocervical dystonia (14), musculoskeletal disorder (15,16), bleeding disorder (9), and cerebellar ataxia (17), respectively. TMEM16A is overexpressed in human gastrointestinal stromal tumors and in head and neck squamous carcinoma; TMEM16G is overexpressed in prostate cancer (18,19). Thus, compounds that modulate the function of TMEM16A have been explored for the treatment of human diseases such as cystic fibrosis, hypertension, secretory diarrheas, asthma, and cancer (20).…”