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Abstract Sperm-associated antigen 9 (SPAG9) is a member of cancer-testis antigen, having characteristics of a scaffold protein, which is involved in the c-Jun N-terminal kinase JNK signaling pathway, suggesting its key involvement in different physiological processes, such as survival, apoptosis, tumorigenesis, and cell proliferation. We identified two families (A and B) having multisystem features like coarse facial features, albinism, cataracts, skeletal abnormalities, and developmental delay. Whole genome sequencing (WGS) in families A and B revealed a homozygous frameshift variant (c.903del; p.Phe301Leufs*2) in the SPAG9 gene. Sanger sequencing of both families revealed perfect segregation of the identified variant in all family members. 3D protein modeling revealed substantial changes in the protein’s secondary structure. Furthermore, RT-qPCR revealed a substantial reduction of SPAG9 gene expression at the mRNA level in the affected individuals of both families, thus supporting the pathogenic nature of the identified variant. For the first time in the literature, biallelic SPAG9 gene variation was linked to multisystem-exhibiting features like coarse facial features, albinism, cataracts, skeletal abnormalities, and developmental delay. Thus, this data supports the notion that SPAG9 plays an important role in a multisystemic disorder in humans.

Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive type of renal-cell carcinoma (RCC). Sperm-associated antigen 9 (SPAG9) has been reported to promote the progression of a variety of tumors and is thus a potential prognostic marker. This study combined a bioinformatics analysis with an experimental validation, exploring the prognostic value of SPAG9 expression in ccRCC patients and the possible underlying mechanisms. The SPAG9 expression was associated with a poor prognosis in pan-cancer patients, but with a good prognosis and slow tumor progression in ccRCC patients. To explore the underlying mechanism, we investigated the roles of SPAG9 in ccRCC and bladder urothelial carcinoma (BLCA). The latter was chosen for comparison with ccRCC to represent the tumor types in which SPAG9 expression suggests a poor prognosis. The overexpression of SPAG9 increased the expression of autophagy-related genes in 786-O cells but not in HTB-9 cells, and SPAG9 expression was significantly correlated with a weaker inflammatory response in ccRCC but not in BLCA. Through an integrated bioinformatics analysis, we screened out seven key genes (AKT3, MAPK8, PIK3CA, PIK3R3, SOS1, SOS2, and STAT5B) in this study. The correlation between SPAG9 expression and ccRCC prognosis depends on the expression of key genes. Since most of the key genes were PI3K-AKT-pathway members, we used the PI3K agonist 740Y-P to stimulate the 786-O cells, to mimic the effect of key-gene overexpression. Compared with the Ov-SPAG9 786-O cells, the 740Y-P further increased the expression of autophagy-related genes by more than twofold. Moreover, we constructed a nomogram based on SPAG9/key genes and other clinical features, which was proven to have some predictive value. Our study found that SPAG9 expression predicted opposite clinical outcomes in pan-cancer and ccRCC patients, and we speculated that SPAG9 suppresses tumor progression by promoting autophagy and inhibiting inflammatory responses in ccRCC. We further found that some genes might cooperate with SPAG9 to promote autophagy, and that these were highly expressed in the tumor stroma and could be represented by key genes. The SPAG9-based nomogram can help to estimate the long-term prognosis of ccRCC patients, indicating that SPAG9 is a potential prognostic marker for ccRCC. [ABSTRACT FROM AUTHOR]

Brain metastases (BM) are the most common brain neoplasm in adults. Current BM therapies still offer limited efficacy and reduced survival outcomes, emphasizing the need for a better understanding of the disease. Herein, we analyzed the transcriptional profile of brain metastasis initiating cells (BMICs) at two distinct stages of the brain metastatic cascade--the "premetastatic" or early stage when they first colonize the brain and the established macrometastatic stage. RNA sequencing was used to obtain the transcriptional profiles of premetastatic and macrometastatic (non-premetastatic) lung, breast, and melanoma BMICs. We identified that lung, breast, and melanoma premetastatic BMICs share a common transcriptomic signature that is distinct from their non-premetastatic counterparts. Importantly, we show that premetastatic BMICs exhibit increased expression of HLA-G, which we further demonstrate functions in an HLA-G/SPAG9/STAT3 axis to promote the establishment of brain metastatic lesions. Our findings suggest that unraveling the molecular landscape of premetastatic BMICs allows for the identification of clinically relevant targets that can possibly inform the development of preventive and/or more efficacious BM therapies. [ABSTRACT FROM AUTHOR]

Abstract Background Dendritic cell (DC)-based immunotherapy is capable of activating the immune system and in particular tumor-specific cytotoxic T lymphocytes (CTLs) to eradicate the tumor. However, major limitations are the availability of autologous tumor cells as antigenic source and the selection of antigen that may have potential to activate both CD4+ and CD8+ T cells in immune-specific manner. Recently, we reported the expression of sperm associated antigen 9 (SPAG9) that is associated with various types of malignancies including cervical cancer. We examined the recombinant human SPAG9 (rhSPAG9) as an antigenic source for generating efficient DCs to stimulate CD4+ and CD8+ T cell responses for future DCs-based vaccine trials in cervical cancer patients. Methods Human monocytes derived DCs were pulsed with different concentrations (250 ng/ml to 1000 ng/ml) of recombinant human SPAG9 (rhSPAG9) and evaluated for their phenotypic and functional ability. The efficacy of DCs primed with 750 ng/ml of rhSPAG9 (SPDCs) was compared with DCs primed with autologous tumor lysates (TLDCs), to induce CD4+, CD8+ T cells and activating NK cells. In addition, we investigated the effect of the chemotherapeutic drug cisplatin on phenotypic and functional potential of SPDCs. Results Phenotypic and functional characterization of DCs pulsed with 750 ng/ml rhSPAG9 was found to be optimal and effective for priming DCs. SPDCs were also capable of stimulating allogeneic T cells similar to TLDCs. SPDCs showed a statistically insignificant increase in the expression of maturation marker CD83 and migration towards CCL19 and CCL21 compared with TLDCs (CD83; P = 0.4; migration; P = 0.2). In contrast, although TLDCs showed better proliferation and secretion of Th1 cytokines (IL12p40, IL12p70 and IFNγ) compared to SPDCs, this difference was not statistically significant (IL12p40, P = 0.06). Further we also observed that clinical dose of cisplatin (200 µM) treated SPDCs were able to stimulate the proliferation of cytotoxic T lymphocytes without increasing the FOXP3+ Tregs in autologous co-cultures. Conclusions In summary, in order to overcome the limitation of the availability of autologous tumor cells as antigenic sources, our present strategy provides an insight to consider rhSPAG9 as a strong immunogen for DC-based immunotherapy for cervical cancer trials and warrants further studies. This is the first report to suggest that rhSPAG9 is an effective antigen for pulsing DCs that are capable of eliciting a potent Th1 response which, in turn, may help in decreasing the tumor burden when used along with a cisplatin based combinatorial regimen for therapeutic intervention.

Background: Cancer/testis antigens are a unique class of tumor antigens with normal expressions restricted to the testis and various cancers, but not in adult somatic tissues. Sperm-associated antigen 9 (SPAG9) has been introduced as a new member of Cancer Testis Antigens family involved in c-Jun-NH2-kinase signaling module. The objective of this research was to investigate the potential of SPAG9 as a diagnostic and prognostic biomarker in breast cancer. We further aimed to find any significant association between SPAG9 expression and clinicopathologic features of the cancer. Methods: In this retrospective study, 35 breast cancer tissues and 35 adjacent non-cancerous tissues were collected and examined using RT-PCR to explore SPAG9 mRNA expression. Statistical analysis was done utilizing SPSS 22.0 software. Results: Unexpectedly, we detected SPAG9 expression in 54% of adjacent non-cancerous tissues. Moreover, SPAG9 mRNA was expressed in 57% of cancerous tissues. Statistical analysis showed a significant association between SPAG9 expression and tumor size, lymph node metastasis, and cancer stage. Conclusion: The association between the gene expression and tumor size, lymph, node and metastasis, and cancer stage suggests that SPAG9 can potentially be considered as a prognostic biomarker in breast cancer. However, it may not be a candidate diagnostic biomarker.

Abstract Background microRNAs (miRNAs) play essential roles in the development and progression of gastric cancer (GC). Although aberrant miR-874 expression has been reported in various human cancers, its role in GC remains obscure. Methods miR-874 expression was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) in 62 matched GC and adjacent normal tissues, as well as in GC cell lines and immortalized human gastric epithelial cells. CCK8 assay, colony formation assay, and flow cytometry were used to assess the role of miR-874 in GC cell proliferation and apoptosis in vitro. Additionally, to determine the effects of miR-874 on GC cell proliferation and apoptosis in vivo, BALB/c nude mice were injected with GC cells transfected with a miR-874 mimic. The role of miR-874 in SPAG9 expression was assessed by luciferase assay, Western blotting, and RT-qPCR. Results miR-874 was downregulated in GC cell lines and tissues. miR-874 overexpression in GC cells led to inhibition of cell proliferation and induction of apoptosis. Moreover, SPAG9 was identified as a direct miR-874 target, the expression of which was suppressed by miR-874. SPAG9 overexpression markedly promoted GC cell proliferation. Conclusions miR-874 inhibited cell proliferation and induced apoptosis in GC cells. SPAG9 downregulation was crucial for the tumor-suppressive effects of miR-874. Hence, the miR-874/SPAG9 axis could serve as a novel therapeutic target in GC.

Background: Dendritic cell (DC)-based immunotherapy is capable of activating the immune system and in particular tumor-specific cytotoxic T lymphocytes (CTLs) to eradicate the tumor. However, major limitations are the availability of autologous tumor cells as antigenic source and the selection of antigen that may have potential to activate both CD4+ and CD8+ T cells in immune-specific manner. Recently, we reported the expression of sperm associated antigen 9 (SPAG9) that is associated with various types of malignancies including cervical cancer. We examined the recombinant human SPAG9 (rhSPAG9) as an antigenic source for generating efficient DCs to stimulate CD4+ and CD8+ T cell responses for future DCs-based vaccine trials in cervical cancer patients. Methods: Human monocytes derived DCs were pulsed with different concentrations (250 ng/ml to 1000 ng/ml) of recombinant human SPAG9 (rhSPAG9) and evaluated for their phenotypic and functional ability. The efficacy of DCs primed with 750 ng/ml of rhSPAG9 (SPDCs) was compared with DCs primed with autologous tumor lysates (TLDCs), to induce CD4+, CD8+ T cells and activating NK cells. In addition, we investigated the effect of the chemotherapeutic drug cisplatin on phenotypic and functional potential of SPDCs. Results: Phenotypic and functional characterization of DCs pulsed with 750 ng/ml rhSPAG9 was found to be optimal and effective for priming DCs. SPDCs were also capable of stimulating allogeneic T cells similar to TLDCs. SPDCs showed a statistically insignificant increase in the expression of maturation marker CD83 and migration towards CCL19 and CCL21 compared with TLDCs (CD83; P = 0.4; migration; P = 0.2). In contrast, although TLDCs showed better proliferation and secretion of Th1 cytokines (IL12p40, IL12p70 and IFNγ) compared to SPDCs, this difference was not statistically significant (IL12p40, P = 0.06). Further we also observed that clinical dose of cisplatin (200 µM) treated SPDCs were able to stimulate the proliferation of cytotoxic T lymphocytes without increasing the FOXP3+ Tregs in autologous co-cultures. Conclusions: In summary, in order to overcome the limitation of the availability of autologous tumor cells as antigenic sources, our present strategy provides an insight to consider rhSPAG9 as a strong immunogen for DC-based immunotherapy for cervical cancer trials and warrants further studies. This is the first report to suggest that rhSPAG9 is an effective antigen for pulsing DCs that are capable of eliciting a potent Th1 response which, in turn, may help in decreasing the tumor burden when used along with a cisplatin based combinatorial regimen for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Purpose: To determine the regulatory role of sperm-associated antigen 9 (SPAG9) in melanoma cell growth. Methods: Immunohistochemical analysis was performed to investigate SPAG9 expression in melanoma tissues. Western blot was used to evaluate SPAG9 expression in melanoma tissues and cells. Melanoma cells were transfected with an siRNA targeting SPAG9 or a SPAG9 overexpression vector. Cell migration and invasion were examined by wound healing and transwell assays. The effects of SPAG9 on the epithelial-mesenchymal transition and mitogen-activated protein kinase (MAPK) pathway in melanoma cells were assessed by western blot. Results: SPAG9 expression was enhanced in melanoma tissues and cells. SiRNA-mediated silencing of SPAG9 repressed melanoma cell migration and invasion, and SPAG9 overexpression contributed to melanoma cell metastasis. In melanoma cells transfected with siRNA-SPAG9, E-cadherin expression decreased while vimentin and matrix metalloproteinase (MMP)-2/9 expression increased. However, ectopic expression of SPAG9 reversed this expression of E-cadherin, vimentin, and MMP-2/9. Silencing of SPAG9 decreased the phosphorylation of MAPKs, including p-p38, p-ERK and p-JNK, in melanoma cells. SPAG9 overexpression upregulated phosphorylation of MAPKs. Conclusion: SPAG9 promotes the migration and invasion of melanoma cells by activating the MAPK pathway. [ABSTRACT FROM AUTHOR]

Background: Cancer/testis antigens are a unique class of tumor antigens with normal expressions restricted to the testis and various cancers, but not in adult somatic tissues. Sperm-associated antigen 9 (SPAG9) has been introduced as a new member of Cancer Testis Antigens family involved in c-Jun-NH2-kinase signaling module. The objective of this research was to investigate the potential of SPAG9 as a diagnostic and prognostic biomarker in breast cancer. We further aimed to find any significant association between SPAG9 expression and clinicopathologic features of the cancer. Methods: In this retrospective study, 35 breast cancer tissues and 35 adjacent non-cancerous tissues were collected and examined using RT-PCR to explore SPAG9 mRNA expression. Statistical analysis was done utilizing SPSS 22.0 software. Results: Unexpectedly, we detected SPAG9 expression in 54% of adjacent noncancerous tissues. Moreover, SPAG9 mRNA was expressed in 57% of cancerous tissues. Statistical analysis showed a significant association between SPAG9 expression and tumor size, lymph node metastasis, and cancer stage. Conclusion: The association between the gene expression and tumor size, lymph, node and metastasis, and cancer stage suggests that SPAG9 can potentially be considered as a prognostic biomarker in breast cancer. However, it may not be a candidate diagnostic biomarker. [ABSTRACT FROM AUTHOR]

Background: microRNAs (miRNAs) play essential roles in the development and progression of gastric cancer (GC). Although aberrant miR-874 expression has been reported in various human cancers, its role in GC remains obscure.Methods: miR-874 expression was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) in 62 matched GC and adjacent normal tissues, as well as in GC cell lines and immortalized human gastric epithelial cells. CCK8 assay, colony formation assay, and flow cytometry were used to assess the role of miR-874 in GC cell proliferation and apoptosis in vitro. Additionally, to determine the effects of miR-874 on GC cell proliferation and apoptosis in vivo, BALB/c nude mice were injected with GC cells transfected with a miR-874 mimic. The role of miR-874 in SPAG9 expression was assessed by luciferase assay, Western blotting, and RT-qPCR.Results: miR-874 was downregulated in GC cell lines and tissues. miR-874 overexpression in GC cells led to inhibition of cell proliferation and induction of apoptosis. Moreover, SPAG9 was identified as a direct miR-874 target, the expression of which was suppressed by miR-874. SPAG9 overexpression markedly promoted GC cell proliferation.Conclusions: miR-874 inhibited cell proliferation and induced apoptosis in GC cells. SPAG9 downregulation was crucial for the tumor-suppressive effects of miR-874. Hence, the miR-874/SPAG9 axis could serve as a novel therapeutic target in GC. [ABSTRACT FROM AUTHOR]

Abstract: Long non‐coding RNAs (lncRNAs) are important regulators of many cellular processes, and their aberrant expression and/or function is associated with many different diseases, including cancer. However, the identification of functional lncRNAs in gastric cancer is still a challenge. In this study, we describe a novel functional lncRNA, linc00483, that is upregulated and associated with tumorigenesis, tumour size, metastasis and poor prognosis in gastric cancer. In our study, linc00483 promoted gastric cancer cell proliferation, invasiveness and metastasis in vitro and in vivo. Mechanistically, upregulated expression of linc00483 in gastric cancer acts as a sponge to absorb endogenous tumour suppressor miR‐30a‐3p. Furthermore, it restores SPAG9 expression, which is negatively regulated by miR‐30a‐3p, and actives MAPK signaling pathway in gastric cancer cells. Thus, linc00483 is an oncogenic lncRNA in gastric cancer and targeting linc00483 or its pathway can potentially be useful in development of targeted therapies for patients with gastric cancer. Our results show that linc00483 is an important regulator in carcinogenesis and may be a useful biomarker to predict prognosis of gastric cancer patients. We believe our findings are novel and will be of interest to scientists working in many areas related to biomarkers in cancer. [ABSTRACT FROM AUTHOR]

Sperm-associated antigen 9 (SPAG9) is a recently characterized oncoprotein that is considered to be involved in several forms of malignant tumor. However, its biological function and expression pattern in human osteosarcoma have not yet been elucidated. In the present study, SPAG9 expression was analyzed in 58 cases of human osteosarcoma by immunohistochemistry. The results demonstrated that SPAG9 was overexpressed in 63.8% (37/58) of osteosarcoma tissues, while normal bone tissues exhibited negative SPAG9 expression. SPAG9 small interfering RNA was employed in the U2OS cell line, which has high endogenous expression, and SPAG9 transfection was performed in the MG63 cell line, which has low endogenous expression. MTT and Matrigel invasion assays demonstrated that SPAG-9-knockdown significantly reduced U2OS cell invasion and proliferation, while SPAG9 transfection enhanced MG63 cell proliferation and invasion. Furthermore, it was observed that SPAG9 positively regulated cyclin D1, phosphorylated-c-Jun NH2-terminal kinase (JNK) and JunD expression. Treatment with the JNK inhibitor, SP600125, abolished the upregulatory effect of SPAG9 on JunD. Taken together, the present study identified SPAG9 as a critical oncoprotein involved in osteosarcoma proliferation and invasion, possibly functioning through JNK-JunD signaling. [ABSTRACT FROM AUTHOR]

Background: Sperm-associated antigen 9 (SPAG9) is upregulated in several malignancies and its overexpression is positively correlated with cancer cell malignancies. However, the specific biological roles of SPAG9 in hepatocellular carcinoma (HCC) are less understood. Methods: We analyzed SPAG9 and ETS-like gene 1, tyrosine kinase (ELK1) expression in 50 paired HCC specimens and adjacent noncancerous liver specimens using immunohistochemistry. SPAG9 small interfering RNA (siRNA) was used to knockdown SPAG9 expression in HCCLM3 and HuH7 cell lines. We used plasmids to upregulate ELK1 expression and siRNA to downregulate ELK1 expression in HuH7 cells. Quantitative real-time polymerase chain reaction and Western blot were used to evaluate the expression of SPAG9 and ELK1 at the mRNA and protein level, respectively. Wound healing, matrigel migration, and invasion analyses were performed to determine the effect of SPAG9 and ELK1 on HCC metastasis. Results: SPAG9 and ELK1 were overexpressed in HCC tissue specimens and their expressions were higher in HCCLM3 and HuH7 cells compared to the low-metastatic HepG2 cells. Overexpression of SPAG9 was positively associated with tumor-node-metastasis staging (P=0.032), metastasis parameters (P=0.018) of HCC patients, and ELK1 expression (r=0.422, P<0.001) in HCC tissue specimens. In addition, knockdown of SPAG9 in HCCLM3 and HuH7 cells using siRNA significantly suppressed cell migration and invasion. Furthermore, we observed inhibition of ELK1 expression and p38 signaling. However, ELK1 overexpression reversed the inhibitory effects of SPAG9 siRNA on HCC cell metastasis and ELK1 depletion inhibited HuH7 cell migration and invasion. Conclusion: SPAG9 overexpression was positively correlated with HCC metastasis and SPAG9-induced migration and invasion were partially dependent on ELK1 expression in HCC cell lines. These results suggest that SPAG9 may be a potential anti-metastasis target effective in HCC therapy. [ABSTRACT FROM AUTHOR]

Background: The aberrant expression of sperm-associated antigen 9 (SPAG9) is associated with numerous cancers, including hepatocellular carcinoma (HCC). The exploration of molecules and mechanisms regulating SPAG9 expression may provide new options for HCC therapy. Methods: MiRNA target prediction programs were used to explore SPAG9-targeted miRNAs. SPAG9 and miR-141 expression were detected in HCC tissues and cell lines by Western blot and real-time PCR. Dual-luciferase reporter assay was utilized to validate SPAG9 as a direct target gene of miR-141. Cell proliferation, invasion, and migration assays were used to determine whether miR-141-mediated regulation of SPAG9 could affect HCC progression. Results: An inverse correlation was observed between SPAG9 and miR-141 expression in HCC tissues and cell lines. Dual-luciferase reporter assay further showed that SPAG9 was a direct target gene of miR-141. The ectopic expression of miR-141 could markedly suppress SPAG9 expression in HCC cells. MiR-141 overexpression also resulted in significantly reduced cell proliferation, invasion, and migration, and imitation of the SPAG9 knockdown effects on HCC cells. Furthermore, SPAG9 restoration in miR-141-expressing cells sufficiently attenuated the tumor-suppressive effects of miR-141. Finally, JNK activity was found to be reduced by miR-141 overexpression the same way as by SPAG9 silencing. The overexpression of SPAG9 lacking its 3'-UTR significantly restored JNK activity and its downstream genes in miR-141-transfected HCC cells. Conclusion: MiR-141 suppression may cause aberrant expression of SPAG9 and promote HCC tumorigenesis via JNK pathway. [ABSTRACT FROM AUTHOR]

Background: Recently, we reported an association of a novel cancer testis (CT) antigen, sperm-associated antigen 9 (SPAG9) expression in breast cancer clinical samples, indicating its potential role in carcinogenesis. Around 15% breast cancers are designated as triple-negative for which treatment modalities are limited. Therefore, in the present study, we assessed the role of SPAG9 in triple-negative breast cancer cells. Methods: SPAG9 mRNA and protein expression was investigated in various breast cancer cells of different hormone receptor status and different subtypes by employing reverse transcriptase-polymerase chain reaction (RT-PCR), real time PCR, Western blotting, indirect immunofluorescence (IIF) and fluorescence activated cell sorting (FACS). Employing plasmid-based small interfering RNA (siRNA) approach, knockdown of SPAG9 was carried out in triple-negative breast cancer cells, MDA-MB-231, to assess its role on various malignant properties in vitro and in vivo. Results: SPAG9 mRNA and protein expression was detected in all breast cancer cells. Further, IIF results showed that SPAG9 was predominantly localized in the cytoplasm of breast cancer cells. FACS analysis revealed distinct SPAG9 surface localization in breast cancer cells. Gene silencing of SPAG9 resulted in significant reduction in cellular proliferation, colony forming ability, migration, invasion and cellular motility of MDA-MB-231 cells. Further, ablation of SPAG9 expression resulted in reduction in the tumor growth of human breast cancer xenograft in nude mice in vivo. Conclusions: In summary, our data indicated that down regulation of SPAG9 reduces growth and invasive potential of triple-negative breast cancer cells, suggesting that SPAG9 may be a potential target for therapeutic use. [ABSTRACT FROM AUTHOR]

SPAG9 is a novel tumor associated antigen, expressed in variety of malignancies. However, its role in ovarian cancer remains unexplored. SPAG9 expression was validated in ovarian cancer cells by real time PCR and Western blot. SPAG9 involvement in cell cycle, DNA damage, apoptosis, paclitaxel sensitivity and epithelial- mesenchymal transition (EMT) was investigated employing RNA interference approach. Combinatorial effect of SPAG9 ablation and paclitaxel treatment was evaluated in in vitro. Quantitative PCR and Western blot analysis revealed SPAG9 expression in A10, SKOV-3 and Caov3 compared to normal ovarian epithelial cells. SPAG9 ablation resulted in reduced cellular proliferation, colony forming ability and enhanced cytotoxicity of chemotherapeutic agent paclitaxel. Effect of ablation of SPAG9 on cell cycle revealed S phase arrest and showed decreased expression of CDK1, CDK2, CDK4, CDK6, cyclin B1, cyclin D1, cyclin E and increased expression of tumor suppressor p21. Ablation of SPAG9 also resulted in increased apoptosis with increased expression of various pro- apoptotic molecules including BAD, BID, PUMA, caspase 3, caspase 7, caspase 8 and cytochrome C. Decreased expression of mesenchymal markers and increased expression of epithelial markers was found in SPAG9 ablated cells. Combinatorial effect of SPAG9 ablation and paclitaxel treatment was evaluated in in vitro assays which showed that ablation of SPAG9 resulted in increased paclitaxel sensitivity and caused enhanced cell death. In vivo ovarian cancer xenograft studies showed that ablation of SPAG9 resulted in significant reduction in tumor growth. Present study revealed therapeutic potential of SPAG9 in ovarian cancer. [ABSTRACT FROM AUTHOR]

Salivary gland cancers are highly aggressive epithelial tumor associated with metastatic potential and high mortality. The tumors are biologically diverse and are of various histotypes. Besides, the detection and diagnosis is a major problem of salivary gland cancer for available treatment modalities. In the present study, we have investigated the association ofsperm associated antigen 9(SPAG9) expression with salivary gland tumor (SGT). Clinical specimens of benign (n= 16) and malignant tumors (n= 86) were examined for theSPAG9expression. In addition, the sera and adjacent non-cancerous tissues (n= 72) from available patients were obtained. Ourin situRNA hybridization and immunohistochemistry (IHC) analysis revealed significant difference (p= 0.0001) inSPAG9gene and protein expression in benign (63%) and malignant tumor (84%) specimens. Further, significant association was also observed betweenSPAG9expression and malignant tumors (P = 0.05). A cut-off value of >10% cells expressing SPAG9 protein designated as positive in IHC, predicted presence of malignant SGT with 83.72% sensitivity, 100% specificity, 100% PPV and 83.72% NPV. Humoral response against SPAG9 protein was generated in 68% of SGT patients. A cut-off value of 0.212 OD for anti-SPAG9 antibodies in ELISA predicted presence of malignant SGT with 69.23% sensitivity, 100% specificity, 100% PPV and 78.94% NPV. Collectively, our data suggests that the majority of SGT show significant difference and association among benign and malignant tumors forSPAG9gene and protein expression and also exhibit humoral response against SPAG9 protein. Hence,SPAG9may be developed as a biomarker for detection and diagnosis of salivary gland tumors. [ABSTRACT FROM PUBLISHER]