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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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    • "Refs. First author, year Antigen Stage Case number Positive number Stage-specific sensitivity (%) Overall sensitivity (%) Specificity (%) [44] Chang, 2005 p53 I 20 6 30 28 a 100 II 54 12 22 III 58 20 35 IV 35 9 26 [16] Suppiah, 2008 p53 I 5 1 20 22 a 100 II 41 9 22 III 41 9 22 IV 4 1 25 [39] Kojima, 2011 p53 I 37 4 11 21 a 93 II 34 9 27 III 58 15 26 IV 13 2 15 [14] Kojima, 2009 p53 I 16 2 13 20 a 100 II 15 2 13 III 14 5 36 IV 0 0 - [21] Lechpammer, 2004 p53 I 28 0 0 18 a 100 II 87 9 10 III 105 9 9 IV 0 0 - [13] Tang, 2001 p53 I 17 1 6 13 a 99 II 439 53 12 III 321 39 12 IV 221 38 17 [60] Chen, 2011 Annexin A I 12 11 92 85 a 62 II 79 63 80 III 91 76 83 IV 38 37 97 [61] Fan, 2011 SEC61b I 10 8 80 79 a 75 II 25 19 76 III 35 29 83 IV 16 12 75 [33] Chen, 2011 RPH3AL I 5 3 60 73 a 84 II 29 18 61 III 34 27 80 IV 16 12 75 [62] Kocer, 2006 MUC5AC I 0 0 - 60 a 73 II 8 4 50 III 11 5 46 IV 11 8 73 [40] Chan, 2010 Panel of five antibody markers b I 7 5 7 1 5 9 a 93 II 34 17 50 III 38 22 58 IV 15 11 73 [20] Chen, 2010 Survivin I 13 8 65 57 a 64 II 86 50 58 III 92 52 57 IV 41 22 54 [51] Benmahrez, 1990 c-myc I 3 1 33 57 a 83 II 20 12 60 III 12 6 50 IV 8 5 63 [68] He, 2009 IMPDH2 I 2 1 50 32 a 100 II 6 1 17 III 14 4 29 IV 3 2 67 [39] Kojima, 2011 CEA I 37 4 11 9 a 94 II 34 3 9 III 58 5 9 IV 13 1 8 [32] Kanojia, 2011 SPAG9 I + II 12 12 100 70 100 III + IV 26 16 62 [35] Chen, 2012 AEG-1 I + II 20 6 30 49 a 100 III + IV 68 37 54 [67] Syrigos, 1999 Tropomyosin I + II 13 5 35 36 a 95 III + IV 32 12 38 "
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