A possible prognostic role of immunoglobulin-G antibody against recombinant Epstein-Barr virus BZLF-1 transactivator protein ZEBRA in patients with nasopharyngeal carcinoma

Abstract

Background. Epstein‐Barr virus BZLF‐1 replication activator (ZEBRA) is involved in the switch from viral latency to a productive cycle. Previous immunofluorescent study has shown that patients with nasopharyngeal carcinoma (NPC) have elevated immunoglobulin‐G (IgG) antibody titres against recombinant ZEBRA protein (ZEBRA/IgG). Methods. The prognostic role of ZEBRA/IgG was further investigated by enzyme‐linked immunosorbent assay (ELISA) in 110 NPC patients under long period of clinical follow‐up. Results. Ninety‐seven percent (85 of 88) of the patients with NPC had significantly higher ZEBRA/IgG titres (geometrical mean titre, i. e., GMT = 8397) than normal Chinese individuals (GMT = 233 and P < 0.0001). Based on Kaplan‐Meier analysis, the actuarial survival in patients with high ZEBRA/IgG titres (25%) after radiotherapy was significantly lower than that of those with low (76%; P = 0.0008) or intermediate titres (62%; P = 0.0036), although the titres taken before treatment did not bear such a relationship. Subdividing the patients into either individual UICC or Ho's stages, those with late‐stage disease (UICC Stage 4 and Ho's Stages 3 and 4) and with high ZEBRA/IgG titres also had poorer prognosis than those with disease of the same stages but who had low titres. Poor prognosis in those with high titres could be associated with a high risk of distant metastasis because consistent titre increase was found in the majority of patients who later developed distant metastasis either in the lung or liver. Only a minimal increase was found in patients with recurrence in the cervical lymph nodes. No consistent increase was observed, however, in patients whose disease was in remission or the majority of those with bone metastasis or local recurrence in the nasopharynx. Conclusion. The postradiotherapy ZEBRA/IgG titre could be a potentially useful marker for differentiating NPC patients with poor prognosis from those at high risk for the development of distant metastasis to the lung or liver.

Sustained elevation of Epstein–Barr virus antibody levels preceding clinical onset of nasopharyngeal carcinoma

“…Cases were separated into three categories (types I, II and III) according to their preclinical serologic profiles: serum VCA IgA of type III cases fluctuated between Xcutoff titre (closed symbols) and o cutoff titre (open symbols) during follow-up; that of type II cases fluctuated initially and rose to Xcutoff titre at or before diagnosis; and that of type I cases were sustained at Xcutoff titre throughout follow-up and at diagnosis. generally in line with anecdotal observations that elevation of EBV antibody levels may precede NPC diagnosis by years in some individuals (Ho et al, 1978a;Zeng et al, 1983;Yip et al, 1994).…”

Identification of Serum Amyloid A Protein As a Potentially Useful Biomarker to Monitor Relapse of Nasopharyngeal Cancer by Serum Proteomic Profiling

“…6 Apart from SAA and serum EBV DNA, a number of other prognostic indicators for NPC, for instance, serum IgG antibody against the EBV ZEBRA protein (45), and DNA flow cytometry that determined tumor proliferative fractions (46) were also identified previously in our institute. By combining protein chip identified biomarkers with these existing indicators, it is possible to establish a multiple-marker prognostic index for monitoring NPC in the future.…”

The prognostic value of IgA/[EBNA1+VCA-p18] on survival of nasopharyngeal cancer patients

“…Nasopharyngeal cancer patients often shows increase in antibody response of IgA and IgG against VCA, EA, EBNA1 and transcription activator Zta and Rta, as well as other EBV lytic cycle protein (Henle and Henle, 1976;Fachiroh et al, 2004). Elevation of antibody responses to EBV may precede onset of clinical manifestation of NPC by 1 to 5 year (Yip et al, 1994;Ji MF et al, 2007). Combined EBV serological biomarkers could improve diagnostic value of NPC (Neel and Taylor, 1990;Fachiroh et al, 2006;Liu et al, 2012;Ai et al, 2013;Chang et al, 2013).…”

“…Combined EBV serological biomarkers could improve diagnostic value of NPC (Neel and Taylor, 1990;Fachiroh et al, 2006;Liu et al, 2012;Ai et al, 2013;Chang et al, 2013). Furthermore, dynamic fluctuation of antibody level after treatment of NPC raised the possibilities of humoral response to be used as prognostic marker (Yip et al, 1994). Specific antibody responses to EBV proteins have become a powerful tool to detect reactivation of this virus in human body.…”