Autoantibodies against tumor-associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display-based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage-antigen microarrays and exploited them for the survey of autoantibody repertoire in patients with GC and inflammatory diseases. We developed procedures for data normalization and cutoff determination to define sero-positive signals and ranked them by the signal intensity and frequency of reactivity. To identify autoantibodies with the highest diagnostic value, a 1,150-feature microarray was tested with sera from 100 patients with GC and 100 cancer-free controls, and then the top-ranked 86 antigens were used for the production of focused array that was tested with an independent validation set comprising serum samples from 235 patients with GC, 154 patients with peptic ulcer and gastritis and 213 healthy controls. The receiver operating characteristic curve analysis showed that 45-autoantibody signature could discriminate GC and healthy controls with area under the curve (AUC) of 0.79 (59% sensitivity and 90% specificity), GC and peptic ulcer with AUC of 0.76 and GC and gastritis with AUC of 0.64. Moreover, it could detect early GC with equal sensitivity than advanced GC. Interestingly, the autoantibody production did not correlate with histological type, H. pylori status, grade, localization and size of the primary tumor, whereas it appeared to be associated with the metastatic disease.Despite the overall global decrease in incidence, gastric cancer (GC) with the estimated $989,600 new cases and $738,000 deaths per year remains the fourth most common type of cancer and the second most common cause of cancer-related death worldwide. 1 The high mortality rate in GC is mostly due to its detection at advanced stage (IIIA-IV), when the estimated 5-year survival rate ranges from 4 to 20% and the median overall survival is around 8-12 months. Only less than 20% of cases are detected at an early localized stage when the complete, curative resection is possible and the 5-year survival rate reaches 75%. 2,3 The early detection of GC is hampered by the lack of specific symptoms before it has spread beyond the original site and the lack of reliable noninvasive screening tests. Currently, the diagnosis is based on endoscopic examination followed by the histological analysis of gastric biopsy, which is an invasive technique not applicable for the screening of asymptomatic population. Hence, the identification and validation of GC biomarkers that could be detected in body fluids such as plasma, serum or urine and that are suitable for the development of noninvasive or minimally invasive tests applicable for screening high-risk groups would represent a significant ste...

Inhibition of CAIX reduces the self-renewal capacity of breast cancer cells, and the combination of doxorubicin and CAIX inhibition is an attractive therapeutic strategy in basal-like and triple-negative breast cancer, which warrants further investigations.

The identification of novel cancer-related and immunogenic proteins is still a challenge to be faced to improve antigen-specific tumor immunotherapy. The category of so-called cancer-testis (CT) antigens is one of the most perspective groups of proteins for anticancer immune response activation as normally they are expressed in immunoprivileged tissues and are immunogenic if aberrantly generated in tumors. The heterogeneous group of proteins called sperm-associated antigens (SPAG) might encompass novel CT antigens owing to their common expression in male germ cells, their ability to elicit immune response underlying infertility, and lately proposed oncogenic properties. We carried out a comprehensive analysis of the expression pattern in various normal and cancerous tissues and assessed the frequency of spontaneous humoral immune response against members of the SPAG group in cancer patients using phage-displayed antigen microarrays. Our results show that out of 15 analyzed SPAG genes only SPAG1, SPAG6, SPAG8, SPAG15, and SPAG17 are predominantly expressed in testis, whereas the others are ubiquitously expressed with only a testis-associated alternative splice variant of SPAG16. mRNA expression of SPAG1, SPAG6, and alternative splice variants of SPAG8, SPAG16, and SPAG17 was elevated in various tumors with frequencies ranging from approximately 10% to 70%. The upregulation of SPAG6 in lung and breast cancer was confirmed by immunohistochemical analysis of tumor and normal tissue microarrays. Cancer-associated spontaneous humoral immune response was detected against SPAG1, SPAG6, SPAG8, and a novel testis-specific splice variant of SPAG17 and ascribe these as novel CT antigens that potentially are applicable as immunotherapeutic targets and serologic biomarkers.

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