Rsf-1 Overexpression Research Articles

RSF-1 overexpression determines cancer progression and drug resistance in cervical cancer

RSF-1 overexpression determines cancer progression and drug resistance in cervical cancer

RSF1 requires CEBP/β and hSNF2H to promote IL-1β-mediated angiogenesis: the clinical and therapeutic relevance of RSF1 overexpression and amplification in myxofibrosarcomas.

Myxofibrosarcoma is genetically complex and lacks effective nonsurgical treatment strategies; thus, elucidation of novel molecular drivers is urgently needed. Reanalyzing public myxofibrosarcoma datasets, we identified mRNA upregulation and recurrent gain of RSF1 and characterized this chromatin remodeling gene. Myxofibrosarcoma cell lines were employed to elucidate the oncogenic mechanisms of RSF1 by genetic manipulation and two IL-1β-neutralizing antibodies (RD24, P2D7KK), highlighting the regulatory basis and targetability of downstream IL-1β-mediated angiogenesis. Tumor samples were assessed for RSF1, IL-1β, and microvascular density (MVD) by immunohistochemistry and for RSF1 gene status by FISH. In vivo, RSF1-silenced and P2D7KK-treated xenografts were analyzed for tumor-promoting effects and the IL-1β-linked therapeutic relevance of RSF1, respectively. In vitro, RSF1 overexpression promoted invasive and angiogenic phenotypes with a stronger proangiogenic effect. RT-PCR profiling identified IL1B as a top-ranking candidate upregulated by RSF1. RSF1 required hSNF2H and CEBP/β to cotransactivate the IL1B promoter, which increased the IL1B mRNA level, IL-1β secretion and angiogenic capacity. Angiogenesis induced by RSF1-upregulated IL-1β was counteracted by IL1B knockdown and both IL-1β-neutralizing antibodies. Clinically, RSF1 overexpression was highly associated with RSF1 amplification, IL-1β overexpression, increased MVD and higher grades (all P ≤ 0.01) and independently predicted shorter disease-specific survival (P = 0.019, hazard ratio: 4.556). In vivo, both RSF1 knockdown and anti-IL-1β P2D7KK (200μg twice weekly) enabled significant growth inhibition and devascularization in xenografts. In conclusion, RSF1 overexpression, partly attributable to RSF1 amplification, contributes a novel proangiogenic function by partnering with CEBP/β to cotransactivate IL1B, highlighting its prognostic, pathogenetic, and therapeutic relevance in myxofibrosarcomas.

RSF-1 overexpression determines cancer progression and drug resistance in cervical cancer.

Background: Remodeling spacing factor 1 (RSF-1/HBXAP) has been linked to a variety of cancer types, however, its roles and the therapeutic potential are not clear in cervical cancer.Methods: RSF-1 expression in cancer tissues was analyzed by immunohistochemical staining followed by statistical analysis with SPSS. Anti-RSF-1 studies were performed by treating cells with specific siRNA or a dominant mutant form (RSF-D4).Results: RSF-1 expression correlates with cancer progression that strongly-positive staining can be found in 67.7% carcinomas and 66.7% CIN lesions, but none in normal tissues. Such overexpression also associated with increased tumor size, poor differentiation, higher nodal metastasis and advanced clinical stages. Kaplan– Meier analysis confirmed that cancer patients with high RSF-1 levels exhibited a significantly shorter survival time than those with low RSF-1 levels. Downregulation of RSF-1 by siRNA silencing or RSF-D4 reduced cell growth and increased drug sensitivity toward paclitaxel treatment in HeLa cells.Conclusions: RSF-1 participates in the tumor progression of cervical cancer and could be considered as an early prognostic marker for cancer development and clinical outcome. Therapies based on anti-RSF-1 activity may be beneficial for patients with RSF-1 overexpression in their tumors.

Overexpression of Rsf-1 correlates with poor survival and promotes invasion in non-small cell lung cancer.

Rsf-1 (HBXAP) was recently reported to play roles in tumorigenesis and tumor progression. There have been many reports referred to Rsf-1 overexpression in various cancers and associated with the malignant behavior of cancer cells. However, the molecular mechanism of Rsf-1 in non-small cell lung cancer aggressiveness remains ambiguous. In the present study, we found that there was a significant association between Rsf-1 overexpression and poor overall survival (p=0.028) in lung cancer. Furthermore, knockdown of Rsf-1 expression in H1299 and H460 cells with high endogenous Rsf-1 expression inhibited cell migration and invasion and downregulated MMP2 expression and nuclear levels of NF-κB. NF-κB inhibitor could also block the effect of Rsf-1 in regulation of MMP2 expression. Further experiments demonstrated that Rsf-1 depletion restrained NF-κB reporter luciferase activity and downregulated bcl-2 and p-IκB protein level. In conclusion, we demonstrated that Rsf-1 was overexpressed in lung cancer and associated with poor survival. Rsf-1 regulated cell invasion through MMP2 and NF-κB pathway.

RSF1 regulates the proliferation and paclitaxel resistance via modulating NF-κB signaling pathway in nasopharyngeal carcinoma.

Purpose: Aberrant expression and dysfunction of RSF1 has been reported in diverse human malignancies. However, its exact role in nasopharyngeal carcinoma (NPC) remains unclear.Methods: The expression of RSF1 mRNA and protein were assayed by qRT-PCR and western blotting, and their correlations with clinicopathological parameters of patients with NPC were further analysed. Lentivirus mediated RSF1 shRNA and RSF1 cDNA were used to knockdown and upregulate the expression of RSF1. CCK8 assays and flow cytometry were applied to monitor the changes of proliferation and paclitaxel sensitivity caused by RSF1 modulation, inhibition of NF-κB pathway by inhibitor Bay 11-7082 and Survivin knockdown. Western blotting was used to detect protein alterations in NF-κB signaling pathway.Results: Our present study demonstrated that both mRNA and protein expressions of RSF1 were increased and correlated with advanced NPC clinical stage. Functional analyses revealed that RSF1 inhibition or overexpression induced changes in cell cycle, apoptosis, and then led to altered proliferation and paclitaxel sensitivity in diverse NPC cells in vitro. Further mechanism investigation hinted that RSF1 overexpression in NPC CNE-2 cells activated NF-κB pathway and promoted the expression NF-κB dependent genes involved in cell cycle and apoptosis including Survivin. Importantly, inhibition of NF-κB pathway by Bay 11-7082 and knockdown its downstream Survivin reversed the paclitaxel resistance caused by RSF1 overexpression.Conclusions: Taken together, our data indicate that RSF1 regulates the proliferation and paclitaxel resistance via activating NF-κB signaling pathway and NF-κB-dependent Survivin upregulation, suggesting that RSF1 may be used as a potential therapeutic target in NPC.

Rsf-1 overexpression serves as a prognostic marker in human hepatocellular carcinoma.

Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 and its clinical significance in human hepatocellular carcinoma (HCC) have not been reported. In the present study, we analyzed the expression pattern of Rsf-1 in human HCC tissues and found that Rsf-1 was overexpressed in 41.1 % of HCC specimens. There was a significant association between Rsf-1 overexpression and tumor stage (p = 0.0322), AFP (p = 0.0184), and tumor relapse (p = 0.0112). Furthermore, Rsf-1 overexpression correlated with poor overall survival in HCC patients (p < 0.001). Rsf-1 overexpression could serve as an independent predictor for poor recurrence-free survival (p = 0.0079). Small interfering RNA (siRNA) knockdown in SK-Hep-1 cells with high endogenous Rsf-1 expression inhibited cell proliferation and colony formation, with downregulation of cyclin E protein. In conclusion, Rsf-1 is overexpressed in HCCs and serves as a novel tumor marker. Rsf-1 contributes to hepatocellular carcinoma cell growth through regulation of cell cycle proteins.

Rsf-1 overexpression in human prostate cancer, implication as a prognostic marker

Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 and its clinical significance in human prostate cancer have not been reported. In the present study, we analyzed the expression pattern of Rsf-1 in human prostate cancer tissues and found that Rsf-1 was overexpressed in 45 % of prostate cancer specimens. There was a significant association between Rsf-1 overexpression and tumor stage (p=0.0039) and preoperative PSA level (p=0.015). Furthermore, Rsf-1 overexpression correlated with poor biomedical recurrence-free survival in prostate cancer patients (p<0.001). Rsf-1 overexpression could serve as an independent predictor for poor recurrence-free survival (p=0.012). In addition, small interfering RNA (siRNA) knockdown in DU145 cells with high endogenous Rsf-1 expression decrease cell proliferation, colony formation, and invasion. In conclusion, Rsf-1 is overexpressed in human prostate cancers and serves as a novel prognostic marker. Rsf-1 contributes to prostate cancer cell growth and invasion, which makes it a candidate therapeutic target.

Abstract A63: Rsf-1, a chromatin remodeling protein, interacts with shelterin protein hRap1 and induces telomere shortening

Abstract Background: Rsf-1, a chromatin remodeling factor that forms an ISWI chromatin-remodeling complex with SNF2H, has been implicated in the oncogenesis of a variety of human cancers, yet its functions in promoting tumor development remains unclear. In this study, we found Rsf-1 interacted with hRap1, a telomere binding protein involved in telomere length regulation. We aimed at characterizing the interaction between Rsf-1 and hRap1 and exploring the effect of Rsf-1 overexpression on telomere length in ovarian cancer cells. Methods: Protein microarray and co-immunoprecipitation were employed to screen and validate Rsf-1 interaction proteins. Deletion mutants of both Rsf-1 and hRap1 were constructed to map the binding domains responsible for their interaction. To determine whether RSF complex was enriched in the telomeric regions, we performed chromatin immunoprecipitation (ChIP) -qPCR in two ovarian cancer cell lines (OVCAR3 with high RSF-1 gene amplification and Rsf-1 inducible SKOV3) with antibodies against Rsf-1 and SNF2H. A ChIP-sequencing dataset performed with Rsf-1 and SNF2H antibodies using OVCAR3 cells was also examined for enrichment of telomeric sequences. To investigate the effect of Rsf-1 overexpression on telomere length, we evaluated by qPCR the telomere length in two Rsf-1 inducible cell lines (SKOV3 and BRK). Results: We identified hRap1, a telomere binding protein, as an interaction partner of Rsf-1 by protein microarray and co-immunoprecipitation. Protein interaction domain mapping revealed that C-terminal domain of hRAP1 and PHD domains and arginine-rich region of RSF1 were critical for this interaction. Both ChIP-qPCR and ChIP-sequencing demonstrated that Rsf-1 and SNF2H were enriched in the telomeres, suggesting that RSF complex was recruited by hRAP1 to the telomeres. Induction of RSF1 expression resulted in shortened telomere length in two different cell lines. The results suggest that RSF complex may be involved in the telomere length regulation mediated by hRAP1. Conclusions: Rsf-1 interacted with hRap1 through the PHD domain and the arginine-rich region. RSF complex bound telomeres, probably through the interaction with hRap1. Rsf-1 overexpression led to telomere length shortening, which may contribute to genomic instability in cancer cells. Citation Format: Ren-Chin Wu, Bin Guan, Yusuke Kobayashi, Tian-Li Wang, Ie-Ming Shih. Rsf-1, a chromatin remodeling protein, interacts with shelterin protein hRap1 and induces telomere shortening. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A63.

Rsf-1/HBXAP overexpression is independent of gene amplification and is associated with poor outcome in patients with urinary bladder urothelial carcinoma

BackgroundsUrothelial carcinoma of the urinary bladder (UCUB) is prevalent in developed countries. It often shows genetic instability and is associated with amplification (or gain) of various oncogenic genes or suppressive...

Rsf-1 overexpression correlates with poor prognosis and cell proliferation in colon cancer

Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 and its biological roles in colon cancer have not been reported. The molecular mechanism of Rsf-1 in cancer aggressiveness remains ambiguous. In the present study, we analyzed the expression pattern of Rsf-1 in colon cancer tissues and found that Rsf-1 was overexpressed in 50.4 % of colon cancer specimens. There was a significant association between Rsf-1 overexpression and TNM stage (p = 0.0205), lymph node metastasis (p = 0.0025), and poor differentiation (p = 0.0235). Furthermore, Rsf-1 overexpression correlated with a poor prognosis in colon cancer patients (p = 0.0011). In addition, knockdown of Rsf-1 expression in HT29 and HCT116 cells with high endogenous Rsf-1 expression decrease cell proliferation and colony formation ability. Further analysis showed that Rsf-1 knockdown decreased cyclin E expression and phospho-Rb level. In conclusion, Rsf-1 is overexpressed in colon cancers and contributes to malignant cell growth by cyclin E and phospho-Rb modulation, which makes Rsf-1 a candidate therapeutic target in colon cancer.

Rsf-1 is overexpressed in non-small cell lung cancers and regulates cyclinD1 expression and ERK activity

Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 in primary lung cancer and its biological roles in non-small cell lung cancer (NSCLC) have not been reported. The molecular mechanism of Rsf-1 in cancer aggressiveness remains ambiguous. In the present study, we analyzed the expression pattern of Rsf-1 in NSCLC tissues and found that Rsf-1 was overexpressed at both the mRNA and protein levels. There was a significant association between Rsf-1 overexpression and TNM stage (p=0.0220) and poor differentiation (p=0.0013). Furthermore, knockdown of Rsf-1 expression in H1299 and H460 cells with high endogenous Rsf-1 expression resulted in a decrease of colony formation ability and inhibition of cell cycle progression. Rsf-1 knockdown also induced apoptosis in these cell lines. Further analysis showed that Rsf-1 knockdown decreased cyclin D1 expression and phospho-ERK levels. In conclusion, Rsf-1 is overexpressed in NSCLC and contributes to malignant cell growth by cyclin D1 and ERK modulation, which makes Rsf-1 a candidate therapeutic target in lung cancer.

Pathogenesis and New Therapeutic Targets of Ovarian Cancer

Ovarian cancer remains the most lethal gynecologic malignancy, largely due to the lack of early detection tools and effective therapeutic interventions. Anti-tumor agents targeting critical molecular pathways hold promise for improving survival in these patients and understanding the critical molecular pathways involved in the pathogenesis of ovarian cancer development is central to the development of such agents. For example, using genome-wide DNA copy number analysis, investigators have identified amplification in a genomic locus (ch11q13.5) harboring a chromatin remodeling gene, RSF1, encoding Rsf-1 in high-grade ovarian serous carcinomas. Recent studies have shown that excessive Rsf-1 expression attributes to genomic instability and alters gene expression profiles to favor tumor growth and survival, especially in the presence of cytotoxic agents. The article entitled “DNA damage response is prominent in ovarian high-grade serous carcinomas, especially those with Rsf-1 (HBXAP) overexpression” reported by M. Kushirsagar et al. in this special issue provides new evidence that Rsf-1 overexpression was correlated with DNA damages which was observed more frequently in high-grade ovarian serous carcinoma. This finding should have several biological and clinical implications for the future studies of Rsf-1 in human cancer.

Associations of Rsf-1 overexpression with poor therapeutic response and worse survival in patients with nasopharyngeal carcinoma

AimsDeregulated chromatin remodelling often leads to aberrant gene expression in cells, thereby implicating tumour development and progression. As a subunit of remodelling and spacing factor complex, Rsf-1 (HBXAP), a novel...

DNA Damage Response is Prominent in Ovarian High-Grade Serous Carcinomas, Especially Those with Rsf-1 (HBXAP) Overexpression

DNA damage commonly occurs in cancer cells as a result of endogenous and tumor microenvironmental stress. In this study, we applied immunohistochemistry to study the expression of phosphorylated Chk2 (pChk2), a surrogate marker of the DNA damage response, in high grade and low grade of ovarian serous carcinoma. A phospho-specific antibody specific for threonine 68 of Chk2 was used for immunohistochemistry on a total of 292 ovarian carcinoma tissues including 250 high-grade and 42 low-grade serous carcinomas. Immunostaining intensity was correlated with clinicopathological features. We found that there was a significant correlation between pChk2 immunostaining intensity and percentage of pChk2 positive cells in tumors and demonstrated that high-grade serous carcinomas expressed an elevated level of pChk2 as compared to low-grade serous carcinomas. Normal ovarian, fallopian tube, ovarian cyst, and serous borderline tumors did not show detectable pChk2 immunoreactivity. There was no significant difference in pChk2 immunoreactivity between primary and recurrent high-grade serous carcinomas. In high-grade serous carcinomas, a significant correlation (P < 0.0001) in expression level (both in intensity and percentage) was found between pChk2 and Rsf-1 (HBXAP), a gene involved in chromatin remodeling that is amplified in high-grade serous carcinoma. Our results suggest that the DNA damage response is common in high-grade ovarian serous carcinomas, especially those with Rsf-1 overexpression, suggesting that Rsf-1 may be associated with DNA damage response in high-grade serous carcinomas.

Rsf-1/HBXAP overexpression is associated with disease-specific survival of patients with gallbladder carcinoma

Dysregulated chromatin remodeling often leads to abnormal gene expression or silencing in cells, thereby implicating tumor development and progression. As a subunit of remodeling and spacing factor (RSF) complex, Rsf-1, a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodeling and confer tumor aggressiveness in common carcinomas. We aimed, for the first time, to evaluate the Rsf-1 expression status and its associations with clinicopathological features and patient survival in a well characterized cohort of gallbladder carcinomas. Using tissue microarray-based immunohistochemistry, we assessed Rsf-1 expression in gallbladder carcinomas, yielding 88 cases undergoing surgical intervention with interpretable results. The Rsf-1 overexpression, present in 61 cases (69.3%), was significantly associated with higher histological grades (p = 0.002) and vascular invasion (p = 0.037) and marginally with non-papillary histotypes (p = 0.058). In univariate log-rank analysis, Rsf-1 overexpression was significantly predictive of disease-specific survival (p = 0.0015), which remained prognostically independent [p = 0.0191, risk ratio (RR) = 2.683], along with American Joint Committee on Cancer stages II-IV (p = 0.0265, RR = 2.102). Our findings indicate that Rsf-1 overexpression is common and associated with adverse prognosticators in gallbladder carcinomas. It may confer tumor aggressiveness through chromatin remodeling and represents a potential prognostic biomarker of gallbladder carcinomas.

Overexpression of a Chromatin Remodeling Factor, RSF-1/HBXAP, Correlates with Aggressive Oral Squamous Cell Carcinoma

RSF-1, also known as hepatitis B X-antigen associated protein (HBXAP), is a subunit of an ISWI chromatin remodeling complex, remodeling and spacing factor (RSF). Recent studies have provided new evidence that chromatin remodeling participates in the pathogenesis of neoplastic diseases by altering cell cycle regulation and gene expression. In this report, we studied the biological roles of RSF-1 in oral squamous cell carcinoma (OSCC), a highly invasive neoplastic disease. Based on IHC and quantitative real-time PCR, we demonstrated that RSF-1 expression could be detected in the majority of OSCC cases, and the levels were significantly higher in OSCC cells than in their normal counterparts. Moreover, expression levels of RSF-1 significantly correlated with the presence of angiolymphatic invasion, abnormal mitoses, metastasis, tumor recurrence, and advanced stage disease at presentation. Univariate and multivariate analyses showed a significant association of RSF-1 overexpression and worse overall survival in OSCC patients. RSF-1 knockdown remarkably decreased cellular proliferation and induced apoptosis in OSCC cells with high RSF-1 expression levels, but not in those without. Taken together, our results suggest that RSF-1 up-regulation is associated with several clinicopathological features of disease aggressiveness in OSCC patients, and RSF-1 plays an important role in maintaining cellular growth and survival in OSCC.

RSF1 Overexpression as an Adverse Prognosticator in Head and Neck Squamous Cell Carcinomas

RSF1 Overexpression as an Adverse Prognosticator in Head and Neck Squamous Cell Carcinomas

The Roles of Human Sucrose Nonfermenting Protein 2 Homologue in the Tumor-Promoting Functions of Rsf-1

Rsf-1 interacts with human sucrose nonfermenting protein 2 homologue (hSNF2H) to form a chromatin remodeling complex that participates in several biological processes. We have previously shown that Rsf-1 gene amplification was associated with the most aggressive type of ovarian cancer and cancer cells with Rsf-1 overexpression depended on Rsf-1 to survive. In this report, we determine if formation of the Rsf-1/hSNF2H complex could be one of the mechanisms contributing to tumor cell survival and growth in ovarian carcinomas. Based on immunohistochemistry, we found that Rsf-1 and hSNF2H were co-upregulated in ovarian cancer tissues. Ectopic expression of Rsf-1 in SKOV3 ovarian cancer cells with undetectable endogenous Rsf-1 expression enhanced hSNF2H protein levels and promoted SKOV3 tumor growth in a mouse xenograft model. Our studies also indicated that induction of Rsf-1 expression affected the molecular partnership of hSNF2H and translocated hSNF2H into nuclei where it colocalized with Rsf-1. Furthermore, analysis of Rsf-1 deletion mutants showed that the Rsf-D4 fragment contained the hSNF2H binding site based on coimmunoprecipitation and in vitro competition assays. As compared with other truncated mutants, expression of Rsf-D4 resulted in remarkable growth inhibition in ovarian cancer cells with Rsf-1 gene amplification and overexpression, but not in those without detectable Rsf-1 expression. The above findings suggest that interaction between Rsf-1 and hSNF2H may define a survival signal in those tumors overexpressing Rsf-1.

Expression of the chromatin remodeling factor Rsf-1 is down-regulated in breast carcinoma effusions

We recently identified Rsf-1, a chromatin-remodeling gene, as a potential oncogene that is frequently amplified and overexpressed in ovarian serous carcinoma, and demonstrated that its expression in carcinoma cells in effusions is associated with poor prognosis. In the present study, we assessed the clinical significance of Rsf-1 overexpression in breast carcinoma effusions. Formalin-fixed paraffin-embedded sections from 47 effusions were analyzed for Rsf-1 expression by immunohistochemistry. Matched primary tumors (n = 30) and solid metastases (n = 26) from 30 patients were additionally studied. Rsf-1 expression in tumor cells in effusions was analyzed for association with clinicopathologic parameters and survival. Rsf-1 protein expression was found in carcinoma cells in 34 (72%) of 47 effusions, 24 (80%) of 30 primary carcinomas, and 24 (92%) of 26 metastases. Rsf-1 immunoreactivity in effusions showed no association with HER-2 or hormone receptor status. Rsf-1 expression level was significantly lower in effusions compared with primary tumors (P = .026 and P = .011 for extent and intensity, respectively) and lymph node metastases (P = .023 and P = .013 for extent and intensity, respectively). Staining extent and intensity were both significantly lower in breast compared with ovarian carcinoma effusions (P = .001 for extent, P < .001 for intensity). Rsf-1 expression showed no association with survival. In conclusion, in contrast to ovarian carcinoma, Rsf-1 expression is down-regulated in breast carcinoma cells in effusions compared with the solid counterparts and has no prognostic role at this anatomic site.

Expression of the chromatin remodeling factor Rsf-1 is upregulated in ovarian carcinoma effusions and predicts poor survival

Objective. We recently identified Rsf-1, a chromatin remodeling gene, as a potential oncogene that is frequently amplified and overexpressed in ovarian serous carcinoma. However, its clinical role in ovarian cancer effusions is not clear. In the present study, we assessed the clinical significance of Rsf-1 overexpression in ovarian carcinoma effusions. Methods. Formalin-fixed paraffin-embedded sections from 168 effusions (134 peritoneal, 34 pleural) were analyzed for Rsf-1 expression using immunocytochemistry. Matched primary tumors ( n = 48) and solid metastases ( n = 73) from 48 patients were additionally studied. Rsf-1 expression in tumor cells in effusions was analyzed for possible association with clinicopathologic parameters and survival. Results. Rsf-1 protein expression was found in carcinoma cells in 157/168 (93%) effusions. Of these, 70 (45%) stained weakly and 87 (55%) strongly. Specimens from patients diagnosed with FIGO stage IV disease had higher staining score (extent × intensity) compared with stage III tumors ( P = 0.008). Rsf-1 expression level was significantly lower in primary tumors and solid metastases ( P < 0.001 for extent, intensity and score). Univariate survival analysis for 59 patients with post-chemotherapy recurrence effusions demonstrated a significant association between higher Rsf-1 staining and shorter overall survival (OS; P = 0.009 for staining extent and intensity, P = 0.02 for staining score). FIGO stage was the only clinical parameter associated with OS in this group ( P = 0.032). In Cox analysis, Rsf-1 expression ( P = 0.022 for staining extent and intensity, P = 0.045 for staining score) and FIGO stage ( P = 0.035) were independent predictors of shorter survival. Conclusions. Rsf-1 is frequently expressed and upregulated in ovarian carcinoma cells in effusions and is a novel prognostic marker for patients with post-chemotherapy recurrent disease. The above findings support a role of Rsf-1 in mediating disease progression and aggressive clinical behavior in this subset of ovarian carcinoma patients.