Prognostic significance of X‐linked inhibitor of apoptosis protein in solid tumors: A systematic review and meta‐analysis

2019 ◽  
Vol 234 (10) ◽  
pp. 18111-18122 ◽  
Author(s):  
Shimeng Li ◽  
Baoxiang Pan ◽  
Lihong Li ◽  
Bo Shi ◽  
Feng Xie ◽  
...  
2018 ◽  
Vol 49 (1) ◽  
pp. 134-143 ◽  
Author(s):  
Cheng-Peng Yu ◽  
Shu-Fang Fu ◽  
Xuan Chen ◽  
Jing Ye ◽  
Yuan Ye ◽  
...  

Background/Aims: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme catalyzing the initial and rate-limiting steps in the kynurenine pathway, which converts tryptophan into kynurenine. Upregulation of IDO1 decreases tryptophan levels and increases the accumulation of kynurenine and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence has shown that IDO1 is highly expressed in various cancer types and associated with poor prognosis of cancer patients. However, the results were inconsistent. Methods: We searched the Web of Science, PubMed, Embase and Cochrane library databases to identify studies evaluating the prognostic value of IDO1 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using fixed-effects/random-effects models. Results: This systematic review and meta-analysis included 2706 patients from 24 articles. The results indicated a shorter overall survival in patients with high expression of IDO1 (hazard ratio [HR] = 2.03, 95% confidence interval [CI]: 1.56-2.63). Furthermore, disease-free survival was worse in patients with high expression of IDO1 (HR = 2.47, 95% CI: 1.46-4.20). Additionally, the pooled odds ratios (ORs) showed that increased IDO1 was significantly associated with tumor differentiation (OR = 1.81, 95% CI: 1.05-3.12), distant metastasis (OR = 1.45, 95% CI: 1.02-2.06), and poor clinical stage (OR = 1.89, 95% CI: 1.13-3.17). However, no significant correlation was observed of increased IDO1 expression with age, sex, lymph node metastasis, and tumor size. Conclusion: High expression of IDO1 is associated with poor clinical outcomes. IDO1 could serve as a biomarker of prognosis and a potential predictive factor of clinicopathology in various cancers. Further studies should be performed to verify the clinical utility of IDO1 in human solid tumors.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15055-e15055
Author(s):  
Fumiya Hongo ◽  
Daisuke Toiyama ◽  
Takashi Ueda ◽  
Yasunori Kimura ◽  
Terukazu Nakamura ◽  
...  

e15055 Background: The X-linked Inhibitor of Apoptosis protein (XIAP) is associated with cell survival by blocking caspase-mediated apoptosis. We have reported the expression and prognostic value of XIAP in human prostate cancer using prostate tissue microarrays (Clin Cancer Res 2007). The expression and prognostic significance of XIAP in renal cell cancer (RCC) has been rarely studied. To our knowledge, no report on the serum XIAP levels from RCC patients has been published. In this study, we examined serum XIAP levels of RCC patients and normal individuals and evaluated its utility as biomarker. Methods: Peripheral blood samples were obtained from 99 patients (68 men and 31 women, median age; 60.7 years [36-85]) with RCC before surgery. All the patients underwent radical or partial nephrectomy. Blood samples were also collected from 52 healthy controls. The histological grade was as follows: grade 1; n= 5, grade 2; n=72, grade 3; n= 22. The serum XIAP levels were measured by a sandwich enzyme-linked immunosorbent assay. Cut off value was calculated by ROC analysis. Results: The serum XIAP levels in patients with RCC were higher than those of normal control individuals (328.3 pg/ml vs 156.2 pg/ml, p<0.001). At a median follow up of 33 months (1-105M), tumor with low serum XIAP showed significantly longer progression free survival (PFS) than those with high serum XIAP in grade 1-2 group (p<0.001). Conclusions: Serum XIAP level is associated with recurrence and prognosis. These results suggest that it may be used as a novel prognosticator and a potential target for renal cell cancer diagnosis and therapy.


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4098
Author(s):  
Stephen Fung ◽  
Wolfram Trudo Knoefel ◽  
Andreas Krieg

Lung cancer is the most common cause of cancer-related death worldwide. Approximately 85% is non-small-cell and 15% is small-cell lung cancer. The inhibitor of apoptosis proteins (IAPs) represent a heterogeneous family of anti-apoptotic proteins, some members of which have been reported to correlate with clinical outcome in lung cancer. We screened PubMed, Web of Science, and Scopus for studies that investigated the prognostic value and clinicopathological features of IAPs in lung cancer. Forty-five eligible studies with 4428 patients assessed the expression of the IAPs survivin, XIAP, livin, and BRUCE. The pooled hazard ratio (HR) of 33 studies that analyzed overall survival (OS) revealed a positive correlation between survivin expression and poor prognosis. Seven studies displayed a strong association between survivin and disease recurrence. Two studies that assessed the expression of XIAP and livin, respectively, proved a significant relationship of these IAPs with poor OS. Meta-analyses of clinicopathological variables revealed a significant association between survivin and T stage, UICC stage, the presence of lymph node metastasis, and grade of differentiation. In conclusion, high expression of distinct IAPs significantly correlates with prognosis in lung cancer. Therefore, lung cancer patients might benefit from a targeted therapy against specific IAPs.


2005 ◽  
Vol 8 (6) ◽  
pp. 621-629 ◽  
Author(s):  
Dae-Kwang Kim ◽  
Carlos S. Alvarado ◽  
Carlos R. Abramowsky ◽  
Lubing Gu ◽  
Muxiang Zhou ◽  
...  

Livin is a recently identified member of the Inhibitor-of-Apoptosis protein (IAP) family of antiapoptosis proteins, and expression has been reported in melanoma and some types of carcinoma. We evaluated livin expression in paraffin-embedded tumor tissue from 68 patients with neuroblastoma (NB) and 7 NB cell lines by immunoperoxidase using an anti-livin monoclonal antibody. Eighteen (26.5%) of the 68 NB tumor tissues showed high livin expression, 36 (53%) showed low-intermediate expression, and 14 (20.5%) were negative. Similarly, 4 NB cell lines showed high livin expression, and 3 showed intermediate expression. In primary NB tissue, livin was observed mainly in tumor neuropil, an extension of tumor cell cytoplasm, and the cytoplasm itself. By reverse transcriptase–polymerase chain reaction, livin expression was confirmed in all 7 NB lines and in frozen tissue from 1 of 3 primary tumors examined to date, in agreement with immunohistochemical data; both livin α and β isoforms were detected. In the NB cases, we further analyzed the correlation between livin expression and clinical and biological features with established prognostic significance (i.e., age at diagnosis, stage, histology, and MYCN oncogene status), and patients' outcome. Livin expression alone did not appear to have an effect on survival; however, patients with high livin expression and amplified MYCN had significantly decreased survival compared with patients lacking both markers or with either of these markers alone. These results suggest that (a) livin is expressed in primary and cultured neuroblastoma cells and (b) high livin expression may identify a subset of neuroblastoma patients with a particularly poor prognosis among those with MYCN amplified tumors.


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