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Background: Previously we found that SPAG5 gene was amplified/gained in 20-35% of HER2+BC. Herein, we investigated the prognostic and predictive significance of SPAG5 (mRNA, protein) expression in 1726 HER+BC patients with median follow-up >5 years. Methods: Analysis of SPAG5 mRNA (cDNA array expression) and protein (immunohistochemistry) and their association with distant relapse risk (DRR) were determined in 446 and 642 cases of HER+2 early stage BC in which 36% and 40% of them had received adjuvant Herceptin (H) + Anthracycline based (AC) + Taxane (T); respectively. In 33% and 31% of SPAG5 mRNA cohort and 21% and 38% of SPAG5 protein cohort had received adjuvant (Adj) AC+T or chemotherapy (CT) naïve; respectively. The association between SPAG5 expression (mRNA, protein) and both pCR and DRR after receiving neoadjuvant chemotherapy (Neo-Adj-CT) were evaluated in 476 and 162 patients with HER2+ locally advanced BC; respectively. Neo-Adj AC+T+HER2 targeting (Herceptin, Herceptin+ Lapatinib or Lapatinib) and AC+/-T has been prescribed to 51% and 49% of mRNA cohort whereas the 45% and 55% of the protein expression cohort has received Neo-Adj AC+T+H and AC+/-T; respectively. Findings: In patients with SPAG5 mRNA overexpression (+;> median), those who had received AC+/-T Neo-Adj-CT alone achieved similar pCR to those who had received AC+T+HER2 targeting Neo-Adj (38% vs., 37%; OR (95% CI): 1.0 (0.6–1.6), p=0.923) in either ER- (46% vs., 52%; OR (95% CI): 1.3 (0.5–3.0), p=0.58) or ER+ subgroups (25% vs., 26%; OR (95% CI): 1.1 (0.4–3.4), p=0.88). Whereas in patients with low SPAG5 mRNA (-), those who had received AC+T+HER2 targeting Neo-Adj had achieved 2.5 fold increased in pCR compared to those who received AC+/-T alone (47% vs., 26%; OR (95% CI): 2.5 (1.4–4.4), p=0.001) in either ER- (60% vs., 31%; OR (95% CI): 3.4 (1.7–6.7), p Conclusion: SPAG5 expression could help in selecting patients who would benefit from both HER2-targeting agents and or AC-CT. Therefore patients with SPAG5- expression could avoid unnecessary AC-CT whereas those with SPAG5+ could receive a shorter Herceptin course. Citation Format: Abdel-Fatah TM, Ball GR, Ellis IO, Chan A, Chan SY. Sperm associated antigen 5 (SPAG5) predicts pathological complete response (pCR) and distant relapse risk to HER2 targeting agents and anthracycline based chemotherapy in HER2 positive (HER2+) breast cancer (BC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-08.

Background For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically. Results The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15–25 nm) and inner diameter (7–8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells. Conclusions The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer. Graphic abstract

Objective Micro RNA (miR)-363 has many important biological functions in cancers, but its roles in esophageal squamous cell carcinoma (ESCC) remain unclear. Methods We used reverse transcription PCR to quantify the expression of miR-363 in 80 ESCC tissues and analyzed its relationship with clinicopathological factors and overall survival. The effects of miR-363 on cell proliferation, apoptosis, and invasion were detected using the MTT assay, flow cytometry, and Transwell invasion assays, respectively. Further, we investigated the post-transcriptional regulation of sperm-associated antigen 5 (SPAG5) expression by miR-363 using luciferase reporter assays. Finally, the effects of SPAG5 on miR-363 were studied by SPAG5 overexpression. Results miR-363 expression was decreased in both ESCC specimens and cell lines, compared with controls, and correlated with lymph node metastasis and tumor differentiation. Low miR-363 expression was identified as an independent prognostic factor for ESCC. miR-363 overexpression decreased ESCC cell proliferation and invasion and increased apoptosis, while the opposite was seen after miR-363 inhibition. Moreover, SPAG5 was identified as a direct target of miR-363, and the reintroduction of SPAG5 restored miR-363-induced effects. Conclusions miR-363 acts as a tumor suppressor by post-transcriptionally regulating SPAG5 expression, suggesting its potential as a diagnostic biomarker and therapeutic target for ESCC.

Background: Esophageal cancer (ESCC) is one of the most common malignant tumors in the digestive system. This study aims to explore the effects of sperm associated antigen 5 (SPAG5) on cell growth, metastasis, and azithromycin resistance in esophagus cancer and its molecular mechanism.Methods: The DEGs were obtained from GSE92396, GSE17351, and GSE9982 datasets about ESCC. The PPI network was constructed using the STRING database and was visualized using Cytoscape software. The cytohubba plug-in of Cytoscape software was used to identify the hub genes of the PPI network. The DEGs were used to perform GO and KEGG pathway enrichment analysis using the DAVID database. Statistical analysis was performed to test the clinical and prognostic significance of SPAG5. Cell viability, proliferation, apoptosis, migration, and invasion were detected using CCK-8, colony formation, flow cytometry, transwell and scratch-wound assays. The expression of related genes was detected by qRT-PCR, western blot and IHC assays. The oncogenicity of SPAG5 in ESCC cells was determined using the nude mouse transplantation tumor experiment.Results: Ninety-three overlapping genes from the DEGs were used to construct the PPI network, and mainly enriched in BP, CC, and MF terms. COX regression analysis of OS showed that SPAG5 expression and pN category were correlated with OS. Univariate and multivariate analyses showed that SPAG5 was an independent prognostic factor for OS in ESCC. The ROC curve analysis showed the AUC of SPAG5 was 0.74. Multiple logistic regression showed that SPAG5 were subsequently identified as an independent risk factor associated with OS. SPAG5 overexpression was detected in ESCC tissues and cell lines, and improved cell proliferation. SPAG5 knockdown reduced cell growth and metastasis and promoted its apoptosis. The functions of SPAG5 overexpression promoting ESCC cell growth and affecting cleaved caspase-3, Ki67, VEGF, and MMP-2/-9 expression were reversed by PI3K/AKT inhibitor. SPAG5 overexpression enhanced resistance to ADM in EC9706 and Eca109 cells and it was closely related to the activation of PI3K/AKT signaling pathway.Conclusion: The overexpression of SPAG5 was an independent good prognostic factor and promoted the proliferation, invasion, migration, and ADM resistance, and inhibited the apoptosis via activating PI3K/AKT signaling pathway in ESCC.

Objectives: Sperm-associated antigen 5 (SPAG5), a spindle-binding protein, regulates the process of mitosis. The present study focused on the relationship between SPAG5 expression and the clinicopathological characteristics and prognosis of ovarian cancer. Methods: First, we used the Gene Expression Omnibus (GEO) database to analyze SPAG5 expression in ovarian cancer and its clinical relevance. Subsequently, qPCR test was used to detect SPAG5 mRNA expression in 20 cases of ovarian cancer. The expression of SPAG5 protein in a tissue microarray containing 102 cases of ovarian cancer was detected by immunohistochemistry. Cox regression and Kaplan–Meier survival analyses were performed to identify the prognostic factors for the 102 ovarian cancer patients. Results: In the GEO datasets, SPAG5 mRNA expression was significantly higher in ovarian cancer tissues than that in normal ovarian tissues (P < 0.001). qPCR and immunohistochemistry showed that SPAG5 expression in ovarian cancer tissues was significantly higher than that in paracancerous tissues (P = 0.002, P < 0.001). The high expression of SPAG5 in ovarian cancer was correlated with histological type (P = 0.009), lymph node metastasis (P = 0.001), distant metastasis (P = 0.001), TNM stage (P = 0.001), and prognosis (P = 0.001). The Kaplan–Meier curve indicated that rates of disease-free survival (DFS) and overall survival (OS) were even lower in patients with high SPAG5 expression. Multivariate analysis showed that SPAG5 expression (P = 0.001) and TNM staging (P = 0.002) were independent prognostic factors for the DFS of ovarian cancer. Conclusions: These results suggest that high SPAG5 expression was correlated with multiple clinicopathological features of ovarian cancer and can be used as an evaluation indicator for a poor ovarian cancer prognosis.

Accumulating evidence has identified microRNA-1179 (miR-1179) as a novel cancer-related miRNA that is dysregulated in multiple cancers and plays an important role in regulating cancer development and progression. However, little is known about the role of miR-1179 in non-small cell lung cancer (NSCLC). Thus, in the present study, we aimed to investigate the potential biological function and regulatory mechanism of miR-1179 in NSCLC. The results showed that decreased expression of miR-1179 expression was frequently detected in primary NSCLC tissues and cell lines. Overexpression of miR-1179 suppressed the growth and invasion of NSCLC cells in vitro while its inhibition promoted the opposite effect. Sperm-associated antigen 5 (SPAG5) was an identified as a target gene of miR-1179. Moreover, SPAG5 expression was increased in NSCLC cells and showed an inverse correlation with miR-1179 in NSCLC specimens. SPAG5 knockdown inhibited the growth and invasion of NSCLC cells, results that simulated a similar effect to miR-1179 overexpression. Mechanistic investigations showed that miR-1179 overexpression or SPAG5 knockdown significantly downregulated the activation of Akt signaling. Additionally, SPAG5 overexpression partially reversed the antitumor effect of miR-1179. Overall, our results demonstrated that miR-1179 inhibited the growth and invasion of NSCLC cells by targeting SPAG5 and inhibiting Akt, findings that highlight the importance of the miR-1179/SPAG5/Akt axis in the progression of NSCCL.

BACKGROUND Sperm-associated antigen 5 (SPAG5), a gene that encodes a mitotic spindle-associated protein, is closely related to tumor development and is involved in cell migration and proliferation. The objective of this research was to explore the clinical significance of SPAG5 expression in hepatocellular carcinoma (HCC) and the relationship between SPAG5 expression and HCC prognosis. MATERIAL AND METHODS Twenty pairs of fresh-frozen HCC samples and samples from 95 HCC patients in a tissue microarray were subjected to quantitative real-time reverse-transcription (qRT)-PCR and immunohistochemistry (IHC), respectively, to investigate the relationship between the expression of SPAG5 and the clinicopathological features of HCC patients. RESULTS PCR data showed that the messenger RNA (mRNA) expression level of SPAG5 in HCC tissue specimens was higher than that in adjacent non-tumor tissue specimens (p

Key Points Question Are sperm-associated antigen 5 (SPAG5) transcript or protein expressions associated with treatment response in patients with estrogen receptor–positive breast cancer? Findings In this cohort study including 12 720 patients with estrogen receptor–positive breast cancer, SPAG5 transcript and SPAG5 protein overexpressions were associated with worse outcomes in patients who received endocrine therapy alone. Overexpressions of SPAG5 transcript or SPAG5 protein were associated with resistance to endocrine therapy but sensitivity to anthracycline-based combination chemotherapy, and downregulation of SPAG5 during the course of preoperative systemic therapies was associated with clinical benefit. Meaning These findings suggest that SPAG5 transcript or SPAG5 protein expression could be used as a clinical tool for selecting and monitoring response to neoadjuvant therapies and guide adjuvant therapy in estrogen receptor–positive breast cancer., This cohort study examines the association of sperm-associated antigen 5 (SPAG5) transcript and protein expression with treatment response in patients with estrogen receptor–positive breast cancer., Importance There is no proven test that can guide the optimal treatment, either endocrine therapy or chemotherapy, for estrogen receptor–positive breast cancer. Objective To investigate the associations of sperm-associated antigen 5 (SPAG5) transcript and SPAG5 protein expressions with treatment response in systemic therapy for estrogen receptor–positive breast cancer. Design, Settings, and Participants This retrospective cohort study included patients with estrogen receptor–positive breast cancer who received 5 years of adjuvant endocrine therapy with or without neoadjuvant anthracycline-based combination chemotherapy (NACT) derived from 11 cohorts from December 1, 1986, to November 28, 2019. The associations of SPAG5 transcript and SPAG5 protein expression with pathological complete response to NACT were evaluated, as was the association of SPAG5 mRNA expression with response to neoadjuvant endocrine therapy. The associations of distal relapse–free survival with SPAG5 transcript or SPAG5 protein expressions were analyzed. Data were analyzed from September 9, 2015, to November 28, 2019. Main Outcomes and Measures The primary outcomes were breast cancer–specific survival, distal relapse–free survival, pathological complete response, and clinical response. Outcomes were examined using Kaplan-Meier, multivariable logistic, and Cox regression models. Results This study included 12 720 women aged 24 to 78 years (mean [SD] age, 58.46 [12.45] years) with estrogen receptor–positive breast cancer, including 1073 women with SPAG5 transcript expression and 361 women with SPAG5 protein expression of locally advanced disease stage IIA through IIIC. Women with SPAG5 transcript and SPAG5 protein expressions achieved higher pathological complete response compared with those without SPAG5 transcript or SPAG5 protein expressions (transcript: odds ratio, 2.45 [95% CI, 1.71-3.51]; P

Background Overexpression of sperm-associated antigen 5 (SPAG5) is a marker of poor prognosis in numerous tumors and is recognized as an index of tumor proliferation; however, its expression in liver cancer remains unclear. Methods The Oncomine (https://www.oncomine.org) and Timer (https://cistrome.shinyapps.io/timer) databases were used to analyze the expression of SPAG5 in liver hepatocellular carcinoma (HCC) and normal liver tissues. The relationship between the expression of SPAG5 and immune infiltration of HCC was investigated using the Timer and GEPIA (http://gepia.cancer-pku.cn) databases, and the mechanism was analyzed using Gene Set Enrichment Analysis. A Kaplan-Meier Plotter (http://kmplot.com/analysis) was used to evaluate the effect of SPAG5 on the prognosis of patients with HCC. Results The results revealed that the SPAG5 expression level was positively correlated with the infiltration levels of CD8+ T cells, macrophages, neutrophils, and especially B cells and dendritic cells. In addition, SPAG5 expression was significantly associated with T cell exhaustion. The overall survival time, progression-free survival time, recurrence-free survival time and disease-specific survival time were significantly reduced for HCC patients with high SPAG5 expression (p 0.05). Additionally, the expression of SPAG5 is related to the p53 and cell cycle signal pathways. Conclusions In conclusion, SPAG5 is not only a marker of immune infiltration and poor prognosis, but also a potential therapeutic target for liver cancer.

Sperm-associated antigen 5 (SPAG5) is involved in the tumorigenesis of multiple cancer types. However, the role of SPAG5 during lung adenocarcinoma (LUAD) progression remains to be fully elucidated. In the present study, the expression of SPAG5 in tumor tissues of patients with LUAD from public cancer databases was analyzed using the online software Gene Expression Profiling Interactive Analysis and University of Alabama Cancer Database. The association of SPAG5 expression levels with the prognosis of patients with LUAD was analyzed using Kaplan-Meier Plotter. In addition, the role of SPAG5 in the LUAD cell line A549 was determined by knocking down its expression with specific small interfering RNA. The results demonstrated that SPAG5 expression was upregulated in LUAD tissues and its high expression was associated with unfavorable prognosis. Furthermore, in A549 cells, SPAG5 promoted proliferation, migration, invasion and autophagy, but inhibited apoptosis. The present results suggest that SPAG5 has an oncogenic role in LUAD and may be a potential prognostic predictor and therapeutic target for LUAD.

Sperm-associated antigen 5 (SPAG5) has currently emerged as a novel oncogene in various cancers. High expression of SPAG5 has been frequently detected in breast cancer. However, the biological function and regulatory mechanism of SPAG5 in breast cancer remain unclear. In this study, we aimed to investigate the potential biological function of SPAG5 in breast cancer cells. Herein, we found that both the mRNA and protein expression of SPAG5 were significantly up-regulated in breast cancer cell lines. Functional experiments showed that silencing of SPAG5 inhibited the proliferation and invasion of breast cancer cells, while the overexpression of SPAG5 promoted the proliferation and invasion of breast cancer cells. Mechanistic investigation demonstrated that SPAG5 promoted the expression of Wnt3 and β-catenin, and increased the activation of β-catenin/TCF4 transcriptional activity. Notably, the inhibition of Wnt3 partially reversed the promotion effect of SPAG5 on breast cancer cell proliferation and invasion and β-catenin/TCF4 signalling. In addition, the inhibition of β-catenin also significantly abrogated SPAG5-mediated oncogenic effects in breast cancer. Taken together, these findings demonstrate that SPAG5 promotes the proliferation and invasion of breast cancer cells by activating Wnt/β-catenin signalling via up-regulating Wnt3 expression.

Sperm-associated antigen 5 (SPAG5) is currently considered to serve a role in promoting tumor cell growth and is overexpressed in several types of human cancer. However, to the best of our knowledge, the association of SPAG5 with molecular subtypes of patients with breast cancer (BC) remains to be fully investigated. Reverse transcription-quantitative polymerase chain reaction and immunohistochemistry on tissue microarrays were used in the current study to detect the expression levels of SPAG5 mRNA and protein, respectively, in BC. The association between SPAG5 mRNA and protein levels, and clinical characteristics and prognostic information were investigated. SPAG5 mRNA and protein levels were identified to be higher in BC tissues compared with matched adjacent nontumor tissues. High expression level of SPAG5 protein was associated with tumor size, histological grade, estrogen receptor expression, Ki-67 expression, lymph node status, tumor-node-metastasis (TNM) stage and the triple-negative BC subtype. In addition, high expression level of SPAG5 protein was associated with a poor prognosis in patients with BC. In summary, the current study suggests that SPAG5 is a novel and useful prognostic biomarker in BC.

1066Background: SPAG5 is an ultimate proliferation marker and important driver that is commonly amplified in “luminal B” BC. Methods: SPAG5 copy number aberrations (CNAs), mRNA and protein expressi...

1040 Background: Clinicopathological implications of SPAG5 were investigated in BC. Methods: SPAG5 copy number changes and gene expression were investigated in 1980 cases of BC (METABRIC cohort) an...

Introduction: SPAG5 has been found to be involved in the functional and dynamic regulation of mitotic spindles, and to be essential for chromosome segregation fidelity. Recently we found by using neural network and pathways analysis of a gene expression array data that SPAG5 was among top 10 ranked genes out of 48,000 of transcripts, that accurately predicted worse clinical outcome based on a 10-fold external cross-validation analysis with an average classification accuracy of >99.999%. Moreover we found that 5% of BC showed amplification of SPAG5 locus at chromosome 17q11.2 and SPAG5 mRNA expression levels displayed a statistically significant correlation with its copy number. Methods: In the current study the molecular and clinicopathological features of SPAG5 expression and its effect on management of BC have been investigated in 2800 BC patients with primary operable invasive BCs constituted four cohorts: 1) A series of 1650 BC patients received adjuvant endocrine and/or CMF chemotherapy according to NPI.2) A series of 256 BC received adjuvant anthracycline-based chemotherapy (ATC-CT)3) A series of 140 primary BC HER2+ patients treated with ATC-CT+ Herceptin 4) To validate SPAG5 as a predictor factor for ATC-CT, 260 patients with locally advanced primary breast cancer treated with neoadjuvant ATC-CT were included and the pathological complete response (pCR) was used to evaluate the response to chemotherapy. Immunohistochemical staining was performed using Anti–SPAG5 rabbit polyclonal (HPA022479; Sigma). Results: i) By using dual immunoflurescent in BC cell lines, co-expression of SPAG5 and proliferating cell nuclear antigen (PCNA) was detected in 4 out of 5 of the breast cancer cell lines screened (MCF7, T47D, MDA468 and MDA231) providing evidence for the importance of SPAG5 in cell proliferation. ii) 20% of breast cancer showed SPAG5 protein overexpression. SPAG5 overexpression showed a statistically significant association with ER−, PR−, triple negative phenotype, high grade tumour, high ki67, basal like phenotype and epithelial mesenchymal transition phenotype, p53 mutation and absence of DNA repair genes (BRCA1, ATM and XRCC1); p values Conclusion: SPAG5 is an important novel gene implicated in the survival of BC cells and its protein expression is an independent predictor for ATC- CT. SPAG5 may provide new avenues for the discovery of new predictive marker to guide therapeutic intervention. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-18.

1098 Background: Recently TOP2A alteration was found to be a predictor for ATC-CT and our neural network analysis of BC gene expression array (GEA) data has revealed SPAG5 gene as a major hubs in both TOP2A and proliferation pathways. In this study the molecular and clinicopathological functions of SPAG5 was investigated in BC and OVC. Methods: (1) A series of 171 BC was evaluated for SPAG5 gene copy number (using aCGH) and mRNA expression (using GEA) which were validated in 5 independent databases. (2) The expression of SPAG5 protein was evaluated pre-clinically in BC and OVC cell lines and in both 40 normal breast tissues and a series of 1650 primary BC and was correlated to clinicopathological and other biomarkers. (3) The association between SPAG5 and response to CT was investigated in a) 350 ER negative BC treated with adjuvant ATC-CT, b) 250 BC treated with neoadjuvant (NEO-A)-ATC-CT, and c) 200 primary OVC treated with cisplatinum based adjuvant CT. Results: (1) 5% and 15% of the 171 BC showed amplification and gain of SPAG5 locus, respectively, at 17q11.2. SPAG5 mRNA expression displayed a significant correlation with its copy number (p< 0.0001). (2) 30% and 20% of ovarian and BC respectively, showed overexpression of SPAG5 protein (+). In BC, SPAG5+ at both mRNA and protein levels showed a significant association with aggressive phenotypes, high mitosis, ER-, high grade, p53 mutation and epithelial mesenchymal transition phenotypes (ps

Breast cancer is a clinically heterogeneous disease, making it imperative to use biomarkers, such as the estrogen receptor (ER) and human epidermal growth factor 2 (HER2), to stratify patients into specific prognostic groups. Biomarker stratification provides patients with more accurate diagnoses, predictions of clinical outcomes, and offers targeted therapeutic options. SPAG5 (Sperm Associated Antigen 5) is involved in the maintenance of spindle-pole integrity, efficient chromosomal alignment, and cell proliferation. Its role in cell division may be a cancer susceptibility factor. Low expression of SPAG5 has been correlated with good prognosis and absence of metastases in ER+ breast cancer. However, its relationship to other molecular subtypes of breast cancer and its functional role in the disease are relatively unknown. The purpose of this study was to investigate the role of SPAG5 in breast cancer through (i) microarray analysis and (ii) correlating its expression with invasiveness, a factor involved in disease progression. In part (i), SPAG5 expression in breast cancers was evaluated by using five Affymetrix, three Agilent and one Illumina microarray datasets. The associations between SPAG5 expression and various tumor pathologies were analyzed via log2 expression ratios. Pathologies that were investigated included the ER+ subtype, HER2 overexpression, lymph node metastasis, and breast cancer stem cell-like/undifferentiated tumors. In part (ii), SPAG5 expression across five breast cancer epithelial cell lines of varying invasive ability (MDA-MB-231, MDA-MB-157, BT549, MCF-7, and CAMA1) was investigated. The cells were cultured at normal conditions and lysed using the CytoBusterTM protein extraction reagent. The supernatants were collected by microcentrifugation at 16,000 rcf at 4°C for 5 minutes. Western blotting was completed using standard techniques. From the microarray analysis, overexpression of SPAG5 showed strong associations with HER2 overexpression, ER-negative and triple-negative cancers, high grade tumors, metastasis, and poor clinical outcomes in a total of 1595 breast cancers. Via immunoblotting, it was shown that higher levels of SPAG5 accompanied highly invasive cell lines (MDA-MB-231, MDA-MB-157, and BT549) and lower levels occurred in weakly invasive cells (MCF-7 and CAMA1). These results suggest that SPAG5 is a biomarker of malignancy and invasiveness and may be a novel therapeutic target for the prevention of metastasis. Stratification into specific prognostic groups using SPAG5 as a biomarker could lead to early detection and intervention of breast cancers likely to metastasize. It is possible that treatments targeting the modulation of SPAG5 expression levels may also aid in improving clinical outcomes. Ongoing functional analysis of SPAG5 will elucidate its role in breast cancer and metastasis and aid in further characterization of SPAG5. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3303.