Fibrous sheath interacting protein 1 overexpression is associated with unfavorable prognosis in bladder cancer: a potential therapeutic target

Abstract

The study aimed to investigate the clinical significance of fibrous sheath interacting protein 1 (FSIP1) in bladder cancer, and its potential relevance to the survival of patients with bladder cancer. A total of 225 surgical excised-bladder cancer tissues were collected from the patients with the follow-up data >5 years. The FSIP1 expressions were assayed using immunohistochemistry. The messenger RNA (mRNA) and/or protein levels of FSIP1 in fresh bladder tumor tissues as well as bladder cancer cell lines were measured by quantitative real-time polymerase chain reaction (PCR) and Western blotting analysis. The correlation of FSIP1 expression with clinicopathological parameters was also evaluated. Western blotting analysis revealed that FSIP1 protein was detected in 94.1% (16/17) of bladder tumor specimens and in all three bladder cancer cell lines (5637, BIU-87, and T24 in particular), with significantly higher expression than those of their controls. Quantitative real-time PCR demonstrated an increased FSIP1 mRNA expression level in bladder cancer tissues than in normal adjacent tissues (P=0.012). FSIP1 overexpression showed good correlation with tumor stage and lymph node metastasis (P=0.027 and 0.000, respectively). Positive FSIP1 expression was independently associated with an unfavorable overall and disease-free survival by multivariate Cox regression (P=0.037 and 0.019, respectively). FSIP1 overexpression is associated with unfavorable prognosis in patients with bladder cancer. Thus, FSIP1 represents a potential therapeutic or predictive target for bladder cancer.

Knockdown of fibrous sheath interacting protein 1 expression reduces bladder urothelial carcinoma cell proliferation and induces apoptosis via inhibition of the PI3K/AKT pathway

“… 19 , 25 Moreover, FSIP1 overexpression was found to induce cancer cell mitotic errors. 25 Indeed, previous studies have shown that FSIP1 was overexpressed in non-small-cell lung carcinoma, 23 breast cancer, 21 and bladder cancer 30 and its overexpression was associated with poor survival in patients carrying these tumors. Thus, FSIP1 is considered to be an oncogene in these cancers.…”

“… 27 – 29 Our published data revealed that FSIP1 protein was significantly upregulated in bladder cancer tissues, and it was associated with unfavorable clinicopathological features as well as poor survival of bladder cancer patients. 30 Thus, further investigation of FSIP1 involvement in bladder cancer could provide a novel insightful information for the role of FSIP1 in the regulation of bladder cancer biological behavior, such as tumorigenesis, progression, and therapeutic strategy.…”

FSIP1 is correlated with estrogen receptor status and poor prognosis

“…In recent years, considerable attention has been deserved to explore novel therapeutic targets of luminal breast cancer . Previous investigations have reported that overexpression of FSIP1 predicted unfavorable prognosis in NSCLC, bladder cancer, and breast cancer . There also is evidence to support that FSIP1 can serve as a potential target for steroid receptor coactivator‐3 in breast cancer, a gene involved in cancer progression and poor prognosis .…”

FSIP1 regulates autophagy in breast cancer

“…Fibrous sheath interacting protein 1 (FSIP1) is a cancer/testis antigen (16) expressed in the majority of breast cancers, bladder cancers, and nonsmall cell lung cancer (17)(18)(19). Our previous findings and those of others show that high FSIP1 expression is associated with increased invasiveness and poor prognosis in breast cancer (19,20).…”