Sperm-associated antigen 9 is a novel biomarker for colorectal cancer and is involved in tumor growth and tumorigenicity.

Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, New Delhi, India.
American Journal Of Pathology (Impact Factor: 4.6). 03/2011; 178(3):1009-20. DOI: 10.1016/j.ajpath.2010.11.047
Source: PubMed

ABSTRACT Colorectal cancer (CRC) is the second most common tumor in developed countries. The present study was undertaken to determine the expression of the sperm-associated antigen 9 gene (SPAG9) as a possible biomarker in CRC, to investigate its correlation with humoral immune response and different stages and grades in CRC patients, and to explore its possible role in colon tumorigenesis in vitro and in an in vivo mouse model. SPAG9 expression was determined by RT-PCR, in situ RNA hybridization, and immunohistochemistry. Humoral response against SPAG9 was detected by enzyme-linked immunosorbent assay and Western blotting. SPAG9 gene silencing was performed using plasmid-based small interfering RNA to study various malignant properties of colon cancer cells in vitro and in vivo. The majority of CRC patients showed SPAG9 expression and generated humoral response. There was a close relationship between SPAG9 protein expression and humoral immune response in the majority of early-stage CRC patients, indicating that anti-SPAG9 antibodies could be a novel serum biomarker for early diagnosis. The down-regulation of SPAG9 (mediated by small interfering RNA) inhibited malignant properties in in vitro and significantly suppressed tumor growth in vivo. These findings collectively suggest that SPAG9 may have a role in tumor development and early spread and thus could serve as a novel target for early detection and for cancer immunotherapy.

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    ABSTRACT: BACKGROUND: Cervical cancer is one of the major gynecologic cancers. In developing countries, because of a lack of medical support and infrastructure, cervical cancer is the leading cause of cancer-related deaths. Therefore, there is a need to identify novel biomarkers for cervical cancers. In this context, cancer-testis (CT) antigens represent a unique class of tumor antigens that have been shown to be associated with various solid tumors. These antigens have restricted expression in testis and no expression in somatic tissues. Because of their restricted expression, CT antigens are novel candidate molecules for early detection and diagnosis and immunotherapy. In the present study, novel CT antigen A-kinase anchor protein 4 (AKAP4) expression and humoral response were investigated in patients with cervical cancer. METHODS: In this study, 74 cervical cancer tissue specimens, which included different tumor stages (stage I [n = 35], stage II [n = 39]) and histologic grades (grade 1 [n = 17], grade 2 [n = 46], and grade 3[n = 11]) and 62 adjacent noncancerous tissue specimens were investigated for AKAP4 gene expression by using reverse transcriptase polymerase chain reaction and in situ RNA hybridization. Furthermore, AKAP4 protein expression was determined by immunohistochemistry. In addition, humoral response against purified recombinant AKAP4 protein was determined in available sera of 70 patients with cervical cancer by enzyme-linked immuno assay (ELISA). FINDINGS: Our study revealed that AKAP4 gene and protein expression was detected in 86% of total patients with cervical cancer. Based on the AKAP4 immunoreactivity score, most of stage I (n = 22/29) and stage II (n = 30/35) specimens revealed high AKAP4 expression (≥50% AKAP4-positive cells). A-kinase anchor protein 4 expression was significantly associated with early grades tumor specimens (P = 0.023). In addition, humoral response was detected in 53% of patients irrespective of stages, lymph node positivity, and grades. CONCLUSIONS: Collectively, our data indicate the putative role of AKAP4 in early tumorigenesis and may be implicated as a biomarker and immunotherapeutic target for cervical cancer.
    International Journal of Gynecological Cancer 03/2013; · 1.94 Impact Factor
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    ABSTRACT: To investigate the expression pattern of SPAG9 protein and its clinical significance in human non-small cell lung cancer (NSCLC). We checked a panel of 120 NSCLC tissues and 20 corresponding normal lung tissues by immumohistochemistry. We observed negative staining in the normal bronchial epithelia and positive staining of SPAG9 in 63 out of 120 (52.5%) NSCLC samples. Overexpression of SPAG9 correlated with poor tumor differentiation (p=0.002), advanced p-TNM stage (p=0.0001), nodal metastasis (p=0.0061) and poor overall survival (p=0.0001). We silenced SPAG9 gene in A549 and H1299 cells by specific siRNA and found that silencing SPAG9 expression inhibited cell growth and invasion. In addition, the protein and mRNA levels of MMP9 were also down-regulated in SPAG9 knocked down cells. Further research demonstrated SPAG9 depletion could inhibit the activity of p-JNK. In conclusion, SPAG9 might act as an important promoter in lung cancer progression and invasion via MMP9 regulation and JNK activation.
    Lung cancer (Amsterdam, Netherlands) 05/2013; · 3.14 Impact Factor
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    ABSTRACT: Sperm-associated antigen 9 (SPAG9) has been suggested as a possible biomarker in several malignancies including thyroid cancer. We investigated the expression of SPAG9 mRNA in fine needle aspiration (FNA) material from papillary thyroid carcinoma (PTC) and benign thyroid nodules. SPAG9 expression was assessed in 36 FNA samples corresponding to 16 PTC and 20 benign nodules using the original method detecting the SPAG9 transcript containing intron 21 (NCBI X91879). The presence of the BRAF V600E point mutation was also analyzed by pyrosequencing. Six of 16 (38%) PTC samples were positive for X91879 SPAG9 transcript compared to 8 of 20 (40%) benign samples (p = 0.88). Out of 12 BRAF-positive PTC, 3 (25%) also expressed the SPAG9 transcript compared to 3 out of 4 BRAF-negative PTC (75%; p = 0.12). The X91879 SPAG9 transcript originally described does not appear to be overexpressed in FNA material from PTC or to be clinically relevant in the diagnosis of thyroid nodules.
    European thyroid journal. 07/2012; 1(2):118-121.

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