Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges

Table 1 Expression and humoral response of SPAG9 in various cancers demonstrating its clinical relevance as a biomarker and mmunotherapeutic target

Cancer	SPAG9 mRNA expressionn (%)	SPAG9 Protein expressionn (%)	SPAG9 expression in matched adjacent non-cancerous tissues	Serological detection of SPAG9 antibodiesn (%)	Expression in cell lines	Clinical relevance and concluding remarks	Ref.
Epithelial ovarian cancer	18 (90)	18 (90)	No	20 (67)	A-10, SKOV-6, Caov-2	No correlation between SPAG9 expression and tumor stages	[76]
Cervical cancer	54 (82)	54 (82)	No	53 (80)	SiHa, HeLa, CaSki, C-33A	SPAG9 expression in cervical tissue specimens was associated with early stages of cervical cancer Ablation of SPAG9 in cervical cancer cells resulted in inhibition of cellular proliferation, migration an invasion in vitro and in vivo	[78,79]
Breast cancer	88 (88)	88 (88)	No	80 (80)	MCF-7, BT-474, SK-BR-3, MDA-MB-231	SPAG9 expression was not correlated with tumor stages but showed significant association with early grades. In addition, High SPAG9 immunoreactivity score correlated with lymphovascular invasion and high risk of recurrence SPAG9 ablation in triple negative breast cancer cells resulted in inhibited cellular proliferation, colony formation , migration and invasion and reduced tumor growth in vivo	[80,81]
Renal cell carcinoma	46 (88)	46 (88)	No	40 (77)	A704, ACHN, Caki-1, Caki-2 NII-AKS395 NII-AKS413 NII-AKS414	SPAG9 expression was significantly associated with lymph node invasion and metastasis in clinical specimens siRNA mediated SPAG9 downregulation inhibited cellular proliferation, migration and invasion in vitro and in vivo	[77]
Thyroid cancer	108 (78)	108 (78)	No (not in multinodal goitres and follicular adenoma samples tested)	92 (78)	WRO, FTC-133, BC-PAP, 8305C	Both SPAG9 expression and humoral response were associated with early stages of thyroid cancer Depletion of SPAG9 resulted in inhibition of cellular growth and colony forming ability of thyroid cancer cells	[82]
Fine needle aspirates of PTC	6 (38) PTC	-	8 (40) benign nodules	-	-	No clinical relevance	[94]
Endometrial cancer	-	Serum SPAG9 antigen (with cut off 17 ng/mL) was used to determine endometrial malignancy (sensitivity = 74%, specificity = 83%)	No SPAG9 levels found in women benign diseases	36 (72)		No significant association of serum SPAG9 antigen levels with histological type, FIGO stage, tumor grade, size, myometrial invasion, lymphovascular space invasion, cervical involvement, adnexal involvement, peritoneal cytology or lymph node status of endometrial tumors Serum SPAG9 levels were found to be negatively correlated with tumor grades	[85,86]
Colorectal cancer	58 (74)	58 (74)	No	38 (70)	COLO 205, HCT 116	SPAG9 expression was correlated with early stages but not with grades, lymph nodes positivity or metastasis SPAG9 expression depletion resulted in decreased tumor growth in vivo and reduced migration and invasion in vitro	[53]
Bladder transitional cell carcinoma	101 (81)	101 (81)	No	96 (77)	HTB-2, HTB-9, HTB-1, UM-UC-3	High SPAG9 expression (> 60% SPAG9 positive cells) was found to be significantly associated with superficial non-muscle invasive stage and low grade tumors In vitro downregulation of SPAG9 caused G0-G1 arrest, inhibition of cellular proliferation, migration and invasion	[84]
Chronic myeloid leukemia	106 (88)	106 (88)	No	106 (88)	K562, KCL-22	No correlation with stages	[83]
Prostate cancer	-	54 (36.5 )	No	-	REPW-1, PC-3, DU-145	SPAG9 expression in clinical specimens is associated with advanced tumor stages and gleason score SPAG9 could supercharge prostate cancer proliferation with cyclin D1 and cyclin E upregulation SPAG9 depletion caused reduction in angiogenesis and migration	[89,90]
Brain cancer (Astrocytoma)	-	63 (60)	No	-	SW1783, SF295, TG905, U251 and U87 (SPAG9 not expressed in A172)	SPAG9 expression was found to positively correlated with tumor grades. SPAG9 depletion was accompanied by downregulation of MMP9 suggesting the possible role of SPAG9 in cellular invasion. PODXL is a critical mediator of the promoting effect of SPAG9 on astrocytoma cell invasion, possibly through upregulation of MMP9 expression	[89,90]
Hepatocellul-ar carcinoma	-	47 (48.5)	No	-		High SPAG9 expression is strongly correlated with multiple tumors, advanced TNM stage, tumor size, serum AFP levels and tumor relapse SPAG9 modulates cell proliferation through cyclin regulation	[91]
Non small cell Lung cancer		63 (52.5)	No	-	A549, H1299	Overexpression of SPAG9 correlated with poor tumor differentiation, advanced p-TNM stage, nodal metastasis and poor overall survival SPAG9 might act as an important promoter in lung cancer progression and invasion via MMP9 regulation and JNK activation	[92]
Non melanoma Skin cancer	-	18 (90) basal cell carcinoma and 18 (82) squamous cell carcinoma	weak SPAG9 expression in 25% normal skin cases	-	-	Significant negative correlation between SPAG9 expression and tumor grade and significantly higher H score values in grade I SCC cases	[93]

EOC: Epithelial ovarian cancer; SPAG9: Sperm associated antigen 9; FIGO staging: Federation of Gynecology and Obstetrics staging; G₀: G₀ phase of cell cycle; G₁: G₁ phase of cell cycle; REPW-1: Human normal prostate epithelial cells; cyclin D1: Cyclin D1protein; cyclin E: Cyclin E protein; SCC: Squamous cell carcinoma; PTC: Papillary thyroid cancer.