Genome-wide copy number variation analysis identified ANO1 as a novel oncogene and prognostic biomarker in esophageal squamous cell cancer

Abstract

Copy number variations (CNVs) represent one of the most common genomic alterations. This study aimed to evaluate the roles of genes within highly aberrant genome regions in the prognosis of esophageal squamous cell cancer (ESCC). Exome sequencing data from 81 paired ESCC tissues were used to screen aberrant genomic regions. The associations between CNVs and gene expression were evaluated using gene expression data from the same individuals. Then, an RNA expression array profile from 119 ESCC samples was adopted for differential gene expression and prognostic analyses. Two independent ESCC cohorts with 315 subjects were further recruited to validate the prognostic value using immunohistochemistry tests. Finally, we explored the potential mechanism of our identified novel oncogene in ESCC. In total, 2003 genes with CNVs were observed, of which 76 genes showed recurrent CNVs in more than three samples. Among them, 32 genes were aberrantly expressed in ESCC tumor tissues and statistically correlated with CNVs. Strikingly, 4 (CTTN, SHANK2, INPPL1 and ANO1) of the 32 genes were significantly associated with the prognosis of ESCC patients. Patients with a positive expression of ANO1 had a poorer prognosis than ANO1 negative patients (overall survival rate: 42.91% versus 26.22% for ANO1−/+ samples, P < 0.001). Functionally, ANO1 promoted ESCC cell proliferation, migration and invasion by activating transforming growth factor-β pathway. Knockdown of ANO1 significantly inhibited tumor progression in vitro and in vivo. In conclusion, ANO1 is a novel oncogene in ESCC and may serve as a prognostic biomarker for ESCC.

Mutational Landscape of Esophageal Squamous Cell Carcinoma in an Indian Cohort

“…In concordance with previously published reports, we observed frequent amplifications in 3q24-26, 8q24, 11q13, 5p15, 9q34, 7q22, 16p13, and 20q11 regions in our cohort (Supplementary Figure 9) (51,64). 11q13.3 region harbors key genes involved in cell growth, such as fibroblast growth factors (FGF3, FGF4, and FGF19) and recently reported oncogenes in ESCC including ANO1 and SHANK2 (65). CNV gains in 3q22-29 region are most frequently observed in ESCC and it contains several key oncogenes, such as PIK3CA, TP63, and SOX2 ( Figure 5).…”

Integrated analysis of genomic and transcriptomic profiles identified a prognostic immunohistochemistry panel for esophageal squamous cell cancer

“…The screening strategy for ESCC prognosis‐associated genes has been previously described . In brief, recurrent somatic CNVs with high frequency (defined as more than three samples) were screened using whole‐exome sequencing data from 81 ESCC samples, and exome sequencing data files are available at the European Genome‐phenome Archive (EGA), under accession EGAS00001000932.…”

“…Moreover, patients with a positive expression of ANO1 had a poorer prognosis, suggesting that ANO1 may contribute to tumorigenesis of ESCC. In our previous study, we found that ANO1 promotes ESCC cell proliferation, migration, and invasion by activating the TGF‐β pathway, suggesting that ANO1 is a novel oncogene and may serve as a potential therapeutic target in ESCC …”

Copy Number Alterations of Depressed Colorectal Neoplasm Predict the Survival and Response to Oxaliplatin in Proximal Colon Cancer

“…Identification of molecular biomarkers to reach the abovementioned aims provides an opportunity to individualize the treatment for subjects with proximal CRC. Growing evidence has demonstrated the effectiveness of copy number alterations (CNAs) in predicting the prognosis of various cancers [16][17][18]. The Cancer Genome Atlas and other genomic landscape studies have explored specific CNAs in CRC, and these molecular alterations may have the potential to predict the prognosis as biomarkers [19,20].…”