Immunogenicity of Ra1A and its Tissue-Specific Expression in Hepatocellular Carcinoma

Abstract

In order to understand the immunogenicity of a tumor-associated antigen (TAA), Ras family small GTP binding protein (RalA) in hepatocellular carcinoma (HCC), autoantibody responses to RalA were evaluated by enzyme-linked immunosorbent assay (ELISA), Western blotting and indirect immunofluorescence assay in sera from patients with HCC and sera from normal individuals. Immunohistochemistry (IHC) study with tissue array slides was also preformed to analyze protein expression profiles of RalA in HCC and control tissues. This study demonstrated that RalA had a relative higher frequency of autoantibody response in HCC (20.1%) compared to liver cirrhosis (3.3%), chronic hepatitis (0%), and normal individuals sera (0%). RalA also showed a stepwise increased expression from normal liver tissues (26.7%), liver cirrhosis tissues (45.0%) to HCC tissues (63.3%). Sensitivity and specificity of anti-RalA antibody in detection of HCC was 20.1% and 99.3%, respectively. The data suggested that RalA might contribute to liver malignant transformation, and could be used as a potential tumor marker in HCC detection.

Evaluation and characterization of anti-RalA autoantibody as a potential serum biomarker in human prostate cancer

“…Furthermore, the IIF signal was significantly reduced when the sera were pre-absorbed with recombinant RalA. The RalA staining in these cells was consistent with previous studies with other cancer cells [23, 27]. …”

“…Evidence indicates that dephosphorylation of RalA is a major mechanism by which PP2A Aβ normally restricts tumor progression, which appears to be a critical step in the Ras-induced transformation and tumorigenesis of human cells [22]. Our recent studies have provided evidence that RalA is overexpressed in hepatocellular carcinoma (HCC), and may have potential as a tumor biomarker in HCC detection [23, 24]. Although the role of RalA in PCa has been noted [25, 26], the immunoreactivity of this protein in PCa patients remains to be investigated.…”

Using immunomic approach to enhance tumor-associated autoantibody detection in diagnosis of hepatocellular carcinoma

“…Six of these 14 TAAs, including RalA, CIP2A/p90, CAPERα, MDM2, NPM1, 14-3-3 ζ were newly added to this TAA array, and the other eight TAAs were same ones as used in our previous study [13]. RalA, CIP2A/p90 and CAPERα were identified and evaluated as TAAs in the previous studies [6–8,24]. Mouse double minute 2 homolog protein (MDM2), also known as E3 ubiquitin-protein ligase, is an important negative regulator of p53 tumor suppressor [38,66].…”

Autoantibodies against tumor-associated antigens for detection of hepatocellular carcinoma

“…In contrast, there are no data available, to our knowledge that associates autoantibodies against p53 with patients' clinical characteristics. In patients with colorectal cancer (CRC), there is an increase in the prevalence of anti-p53 autoantibodies in carcinoma in-situ (6%) compared with adenomas (1%), indicating that the level of anti-p53 autoantibody increases with CRC [36] hnRNP L Akada et al [42] HSP70, SOD2, and PRDX6 Shao et al [41] Glucose-regulated protein 78 Nomura et al [39] Ku86 Liu et al [40] CENPF, DDX3, HSPA4, HSPA5, VIM, LMNB1, and p53 Pekáriková et al [21] CRT Chen et al [28] Sui1, RalA Wang et al [43] KRT23, AHSG and FTL Wang et al [44] RalA Looi et al [45] HSP60, HSP70 Li et al [35] DDX3, eEF2, AIF, hnRNP A2, PBP, and TIM Chen et al [46] EIF3SI, LDHA, RFC2, and MCART1 Zhang et al [27] IMP1, IMP2, IMP3, p53, c-myc, cyclin B1, survivin and p16 Akere et al [13] p53 Zhou et al [47] HCC-22-5 Takashima et al [48] HSP70, GAPDH, PRX, Mn-SOD Looi et al [49] p16 Yagihashi et al [25] Survivin Su et al [17] IMP2 Himoto et al [19] IMPs Himoto et al [18] IMPs, p53, c-myc, and survivin Zhang et al [24] c-myc, cyclin B1, IMP1, Koc, p53, IMP2, and survivin Soo Hoo et al [50] p53, IMP2, Koc, CENP-F, p90 Le Naour et al [51] CRT, CK8, NDK-A, and ATP5B Zhang et al [23] IMP2, CENPF Zhang et al [20] IMP2 Raedle et al [52] p53 Covini et al [22] Cyclin B1 Imai et al [53] HCC1 TAAs: Tumor-associated antigens; HCC: Hepatocellular carcinoma; IMP: Insulin-like growth factor mRNA-binding; CENPF: Centromere protein F. 9…”