Survivin and XIAP expression in distinct tumor compartments of surgically resected gastric cancer: XIAP as a prognostic marker in diffuse and mixed type adenocarcinomas

Abstract

Abstract. There is considerable evidence that the inhibitor of apoptosis protein (IAP) family serves a role in tumorigenesis. The most studied IAP family members, survivin and X-linked inhibitor of apoptosis (XIAP), have been demonstrated to serve as biomarkers in distinct tumor entities. Thus, the present study aimed to investigate the expression levels of both IAPs in the tumor center, invasion front and lymph node metastases of surgically resected gastric cancer (GC) specimens. Tissue microarrays containing samples from 201 primary GCs were analyzed. IAP expression was detected using immunohistochemistry in different tumor compartments, normal mucosa and lymph node metastases. In addition, the association between the expression levels of these proteins, and clinicopathological parameters and overall survival was investigated. High levels of survivin and XIAP were evident in GC, when compared with normal mucosa, and were correlated with intestinal-type and well-differentiated GC, as well as low International Union Against Cancer stages. Increased XIAP expression was detected in lymph node metastases as compared with corresponding primary tumors. XIAP overexpression was identified to be an independent negative prognostic marker in diffuse and mixed type GC. These results suggest a potential role of survivin and XIAP in the early phase of gastric carcinogenesis. In addition, increased XIAP expression in lymph node metastases supports the observation that IAPs serve an essential role in metastatic tumor disease. Since XIAP expression was identified to be associated with poor survival in diffuse and mixed type GC, XIAP may serve as a novel therapeutic target in these types of GC.

Prognostic Value of XIAP Level in Patients with Various Cancers: A Systematic Review and Meta-Analysis

“…All studies were retrospective design and the sample size ranged from 29 to 1103. The patients were diagnosed with various solid carcinomas, among which digestive tumors accounted for the most type, particularly gastric cancer (n=4) 25-28, colorectal cancer (n=3) 29-31, HCC (n=5) 12, 17, 32-34, esophageal cancer (n=2) 11, 35, cholangiocarcinoma (n=2) 36, 37 and pancreatic cancer (n=1) 38. And the remaining studies included breast cancer (n=4) 16, 18, 19, 39, NSCLC (n=2) 13, 40, head and neck cancer (HNC) (n=4) 41-44, thyroid cancer (n=4) 15, 45-47, prostate cancer (n=2) 14, 48, renal cancer (n=2) 49, 50 and other tumor types (n=5) listing as: sebaceous gland carcinoma, glioblastomas, ovarian cancer, bladder cancer and malignant mesothelioma 51-55.…”

Prognostic significance of X-linked inhibitor of apoptosis protein in patients with gastrointestinal tract cancers

“…The rest studies were further evaluated in full text and 31 were excluded due to unrelated, lacking enough data or other reasons. Eventually, 12 studies [ 12 , 14 – 22 , 24 , 25 ] met the inclusion criteria and were included. The study selection process was shown in Figure 1 .…”

“…This phenomenon may suggest different roles of XIAP in squamous cell carcinoma and adenocarcinoma. Dizdar et al [ 22 ] also investigated the prognostic role of XIAP in gastric cancer. Although the pooled HR from multivariate analysis was not significant in all subtypes of gastric cancer, they found that XIAP could be an independent prognostic marker in both diffuse type and mixed type of gastric cancer.…”

“…However, the results were not statistically significant in other studies. [ 15 , 22 ] Due to the controversy, the aim of this study was to systematically evaluate the prognostic value of XIAP in patients with GIT cancers through performing a meta-analysis.…”

The Biological Activities and Therapeutic Potentials of Baicalein Extracted from Oroxylum indicum: A Systematic Review

“…Moreover, XIAP and survivin are members of the inhibitor of apoptosis (IAP) protein family that inhibit caspases and block cell death. These proteins are highly expressed in most types of cancer cell and are associated with a poor clinical cancer treatment outcome [19]. The overexpression of these four proteins in cancer cells may block or delay the onset of apoptosis by selecting and maintaining the long-living cancer cells in the G0 phase of the cell cycle.…”