Expression of IFITM1 as a prognostic biomarker in resected gastric and esophageal adenocarcinoma

Abstract

BackgroundThere is an increasing amount of reports on IFITM1 (interferon-inducible transmembrane protein 1) in various malignancies. The aim of this study was to examine the expression of IFITM1 and its prognostic significance in gastroesophageal adenocarcinoma.MethodsTissue samples were obtained from a consecutive cohort of 174 patients surgically treated between 2006 and 2010 for gastroesophageal (gastric, gastroesophageal junction and esophageal) adenocarcinoma, not subjected to neoadjuvant therapy. Expression of IFITM1 was examined using immunohistochemistry on tissue microarrays of primary tumors and paired samples of adjacent normal epithelium, intestinal metaplasia and lymph node metastases.ResultsExpression of IFITM1 was significantly elevated in primary tumors and lymph node metastases compared to adjacent normal epithelium and intestinal metaplasia, regardless of tumor location. Overexpression of IFITM1 was associated with M0-disease (no distant metastases). In gastric cancer IFITM1 expression was significantly associated with improved TTR (time to recurrence) in Kaplan-Meier analysis and Cox regression, both in the unadjusted analysis (HR 0.33, 95 % CI 0.12-0.88) and in the adjusted analysis (HR 0.32, 95 % CI 0.12-0.87) but there was no significant impact on OS (overall survival). In esophageal adenocarcinoma expression of IFITM1 had no impact on TTR or OS in Kaplan-Meier-analyses, but in the adjusted Cox regression IFITM1 expression had a negative impact on both TTR (HR 3.05, 95 % CI 1.09-8.53) and OS (HR 2.71, 95 % CI 1.11-6.67).ConclusionsIFITM1 was overexpressed in gastroesophageal adenocarcinoma and associated with M0-disease. In gastric cancer IFITM1 expression had a positive impact on TTR but in esophageal cancer it seemed to have an adverse impact on survival.The reason for the diverging prognostic impact of IFITM1 in esophageal and gastric cancer is unclear and warrants further studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s40364-016-0064-5) contains supplementary material, which is available to authorized users.

Identification of IFITM1 with prognostic value in pancreatic cancer using network module-based analysis

“…To further validate the prognostic signature of IFITM1 in pancreatic cancer patients, both univariable and multivariable Cox regression analysis were assessed and the data suggested IFITM1 an independent prognostic marker. This similar prognostic values were also seen in other type of tumors [41,43,49].…”

“…The difference was also observed in two other studies demonstrated IFITM1 overexpression through patients' tissues and lung cancer cell lines [6,40]. Immunohistochemistry on TMA of a consecutive cohort including 174 gastroesophageal adenocarcinoma patients also detected a signi cant elevation of IFITM1 in primary tumors along with lymph node metastases, compared to the adjacent normal epithelium and intestinal metaplasia [41]. Notably, histologic differentiation (P = 0.032) and tumor stage (P = 0.044) of the pancreatic cancer patients were signi cantly correlated with IFITM1 expression in the clinical and pathological analyses.…”

The effects of IFITM1 and IFITM3 gene deletion on IFNγ stimulated protein synthesis

“…a model of metastatic growth) [16]. Consistent with this, using clinical material IFITM1 protein has often been shown in literature to be over-produced in cancers using immunohistochemistry and this often correlates with poor prognosis [12,52].…”

“…IFITM1 is up-regulated during development of radiation resistance, escaping from pro-apoptotic and anti-proliferative effects [9,10]. IFITM1 expression has been extensively reported in many types of cancer; breast, cervix, colon, ovary, brain and oesophagus cancer and its high expression correlates with tumor progression and can lead to a poor outcome [10][11][12][13][14][15][16].…”

“…IFITM1 was previously known as IFI 17 (interferon induced protein 17), IFI 9-27 (interferon inducible protein [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27], CD225 (cluster of differentiation) and Leu-13 (leucocyte surface protein). It is a membrane protein that plays a key role in restriction of anti-viral immune response and belongs to the interferon induced transmembrane family (IFITM) [17].…”