Prognostic significance of TMEM16A, PPFIA1, and FADD expression in invasive ductal carcinoma of the breast

Abstract

Background11q13 region is a frequently amplified locus in human malignancies. Among the genes located in this region, FADD is one of the alleged driving genes. Because amplification is not generally confined to a single gene and amplified genes may not show increased expression, we need to evaluate clinical significance of changes occurring in 11q13 region to understand their roles in carcinogenesis. Therefore, we screened expressions of FADD and closely located genes (PPFIA1 and TMEM16A) and evaluated the expressions to find clinical significance in invasive ductal carcinoma of the breast.MethodsNinety-eight cases of invasive ductal carcinoma of the breast were collected. Using archival tissues resected from the cases, we built a tissue microarray and used it in immunohistochemistry. We evaluated the association of FADD, PPFIA1, and TMEM16A expression scores with clinicopathological parameters, including disease-free survival.ResultsFADD expression was associated with T stage (P = 0.046). The combined score of FADD, PPFIA1, and TMEM16A gene expressions was associated with perineural invasion (P = 0.022). Although individual gene expressions of TMEM16A, FADD, and PPFIA1 failed to show significant association with disease-free survival, combined gene expression scores did show association with disease-free survival (P = 0.034).ConclusionsFADD, TMEM16A, and PPFIA1 gene expressions as a whole were associated with disease-free survival in breast cancer.

Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer

“…Concomitant amplification of the 11q13 region in HNSCC [ 39 ] and over expression of FADD have, in combination, suggested this gene to be the driver of this amplicon [ 40 ]. As observed in this study, both these genes, in combination, are also identified to be predictive of prognosis in breast cancers [ 41 ]. Identification of these two genes from this cross-study/cross-platform analysis, necessitates detailed investigation as to their role in the disease and their clinical applicability as biomarkers and/or therapeutic targets.…”

Assessment of Tumor Heterogeneity, as Evidenced by Gene Expression Profiles, Pathway Activation, and Gene Copy Number, in Patients with Multifocal Invasive Lobular Breast Tumors

“…Copy number data for this region are shown in Fig 2 . 11q13.3 amplification has been previously described in breast cancer,[ 26 , 27 ] specifically ILC, [ 28 – 30 ] and in oral squamous carcinoma where it was reported as prognostic of metastasis [ 31 ]. Within our dataset, amplifications were identified in CCND1 , FADD and ORAOV1 in all three punches from both foci.…”

Knockdown of TMEM16A suppressed MAPK and inhibited cell proliferation and migration in hepatocellular carcinoma

“… 7 The upregulation of TMEM16A has also been shown in several cancers, such as breast and prostate cancer, 8 head and neck squamous cell carcinoma (HNSCC), 9 esophageal squamous cell cancer, 10 and human colorectal cancer. 11 It has been shown that TMEM16A activated the MAPK signaling proteins, and promoted the tumorigenesis and invasion of various cancers, such as HNSCC, 6 breast cancer, 12 , 13 and gastrointestinal stromal tumors. 14 However, the expression and role of TMEM16A in hepatocellular carcinoma have not been evaluated to date.…”