Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

Abstract

Background The BIRC5 gene encodes for the Survivin protein, which is a member of the inhibitor of apoptosis family. Survivin is found in humans during fetal development, but generally not in adult cells thereafter. Previous studies have shown that Survivin is abundant in most cancer cells, thereby making it a promising target for anti-cancer drugs and a potential prognostic tool. Methods To assess genetic alterations and mutations in the BIRC5 gene as well as BIRC5 co-expression with other genes, genomic and transcriptomic data were downloaded via cBioPortal for approximately 9000 samples from The Cancer Genome Atlas (TCGA) representing 33 different cancer types and 11 pan-cancer organ systems, and validated using the ICGC Data Portal and COSMIC. TCGA BIRC5 RNA sequencing data from 33 different cancer types and matching normal tissue samples for 16 cancer types were downloaded from Broad GDAC Firehose and validated using breast cancer microarray data from our previous work and data sets from the GENT2 web-based tool. Survival data were analyzed with multivariable Cox proportional hazards regression analysis and validated using KM plotter for breast-, ovarian-, lung- and gastric cancer. Results Although genetic alterations in BIRC5 were not common in cancer, BIRC5 expression was significantly higher in cancer tissue compared to normal tissue in the 16 different cancer types. For 14/33 cancer types, higher BIRC5 expression was linked to worse overall survival (OS, 4/14 after adjusting for both age and tumor grade and 10/14 after adjusting only for age). Interestingly, higher BIRC5 expression was associated with better OS in lung squamous cell carcinoma and ovarian serous cystadenocarcinoma. Higher BIRC5 expression was also linked to shorter progressive-free interval (PFI) for 14/33 cancer types (4/14 after adjusting for both age and tumor grade and 10/14 after adjusting only for age). External validation showed that high BIRC5 expression was significantly associated with worse OS for breast-, lung-, and gastric cancer. Conclusions Our findings suggest that BIRC5 overexpression is associated with the initiation and progression of several cancer types, and thereby a promising prognostic biomarker.

Role of hypoxia-inducible factor-1α and survivin in breast cancer recurrence and prognosis

“…HIF-1α is overexpressed in various cancers and that its action activates tumor cell angiogenesis, supplying oxygen and nutrients to promote their growth and proliferation, invasion, and metastasis [ 17 ]. Survivin is expressed in a variety of tumor cells, which can promote the apoptosis of tumor cells and has a strong function in apoptosis-related signal pathways [ 18 ]. Few studies have linked these two indicators; therefore, this study examined how they are related in breast cancer.…”

Single-cell analysis of CX3CR1+cells reveal a pathogenic role for BIRC5+myeloid proliferating cells driven byStaphylococcus aureusleukotoxins

“…Due to its role in cell cycle progression, BIRC5 has been hypothesized to be an important biomarker of many cancers. Indeed, multiple studies have shown a positive correlation between expression levels of BIRC5 in different tumors and a poorer prognostic outcome (15,16,29–31). Furthermore, while not true for all cancers, many tumors displayed a positive correlation between BIRC5 expression and immune cell infiltration, suggesting a potential immunogenic role for BIRC5 (15,31).…”

Gender Dimorphism in Hepatic Carcinogenesis-Related Gene Expression Associated with Obesity as a Low-Grade Chronic Inflammatory Disease

“…These data were consistent with a previously detected increase in SURVIVIN/BIRC5 in the visceral adipose tissue of male animals with obesity and blood leukocytes in humans [ 30 ]. In fact, in recent years, this oncogene has generated great interest as a biomarker of prognostic importance and therapeutic relevance in many malignant neoplasms such as HCC [ 33 , 50 , 51 , 52 ]. Thus, SURVIVIN/BIRC5 overexpression has been associated with the onset and progression of several types of cancer [ 40 , 50 , 53 , 54 , 55 ], and, regarding HCC, the expression of SURVIVIN/BIRC5 has been reported in 41% of cases and its high expression has been associated with a poor prognosis in patients [ 40 , 56 , 57 , 58 ].…”

“…In fact, in recent years, this oncogene has generated great interest as a biomarker of prognostic importance and therapeutic relevance in many malignant neoplasms such as HCC [ 33 , 50 , 51 , 52 ]. Thus, SURVIVIN/BIRC5 overexpression has been associated with the onset and progression of several types of cancer [ 40 , 50 , 53 , 54 , 55 ], and, regarding HCC, the expression of SURVIVIN/BIRC5 has been reported in 41% of cases and its high expression has been associated with a poor prognosis in patients [ 40 , 56 , 57 , 58 ]. In addition, to the best of our knowledge, this is the first study to evidence sex differences in the expression of the SURVIVIN/BIRC5 oncogene associated with the state of obesity, which was detected even before the manifestation of a tumor mass in the liver.…”