Abstract
Exosomes have emerged as novel vehicles for proteins and other contents in cancer progression. Cyclophilin A (CYPA) is a pivotal member of immunophilin family. Whether CYPA can be detected in sera of nasopharyngeal carcinoma (NPC) patients remains to be explored. Epstein‐Barr virus (EBV) is the first identified human tumor virus and is a causative agent of NPC. The antibody of EBV capsid antigen immunoglobulin A (EBV‐VCA‐IgA) is a known biomarker of NPC, with a proportion of no more than 70% being detected positively. Hence, novel biomarkers need to be discovered for early diagnosis, prognosis, and monitoring of EBV‐associated NPC. A total of 110 NPC and 36 normal control serum samples were collected. Exosomes from these samples were extracted. The mRNA and protein expression levels of the above samples were validated by reverse transcription –quantitative polymerase chain reaction, Western blotting, or enzyme‐linked immunosorbent assay (ELISA). Finally, the results demonstrated that both the serum and exosomal CYPA levels of NPC patients were significantly higher than that of normal cases. In addition, exosomal CYPA had a much higher level than that in the whole sera. The positive rate of EBV‐VCA‐IgA antibody was 68.2% in NPC sera, and noticeably, among the cases with EBV‐VCA‐IgA negative, 80% of them presented high levels of CYPA above the standard (cutoff value). In particular, CYPA in exosomes was uniformly with higher significance than that in whole sera. Combined analysis of CYPA protein and EBV‐VCA‐IgA antibody showed a greatly higher discriminatory ability in diagnosis of NPC. Moreover, exosomal CYPA level had a positive correlation with that of the EBV‐encoded latent membrane protein 1 (LMP1) in exosomes. EBV‐positive cancer cells secreted significantly higher levels of exosomal CYPA. This study established the utility of circulating exosomal CYPA as a potential noninvasive diagnostic biomarker for EBV‐associated NPC.
Highlights
Nasopharyngeal carcinoma (NPC), especially the undifferentiated subtype, is epidemic in southern China.[1]
It has been shown that age‐standardized incidence rates (1970‐2007) of NPC reduced significantly in epidemic areas by −0.9%‐−5.4% in males and −1.1%‐−4.1% in females every year in average, owing to lifestyle changes and economic development and another study revealed that age‐standardized mortality rates (1970‐2013) declined varying from −0.9% to 3.7% and −0.8% to −6.5% in males and females, respectively
NPC is curable when diagnosed early and its 5‐year survival could be reached as much as 90%
Summary
Nasopharyngeal carcinoma (NPC), especially the undifferentiated subtype, is epidemic in southern China.[1]. It has been shown that age‐standardized incidence rates (1970‐2007) of NPC reduced significantly in epidemic areas by −0.9%‐−5.4% in males and −1.1%‐−4.1% in females every year in average, owing to lifestyle changes and economic development and another study revealed that age‐standardized mortality rates (1970‐2013) declined varying from −0.9% to 3.7% and −0.8% to −6.5% in males and females, respectively These changes are probably due to diagnostic accuracy and combination of diverse treatment approaches including the radiotherapy techniques.[2] distant metastasis remains a major issue. Exosomes contain DNA, RNA, proteins and other bioactive molecules, playing roles in exchanging genetic information and regulating physiological and pathological activities.[18,19] Emerging studies have proven that exosomes released from tumor cells can affect tumor formation, growth, angiogenesis, metastasis, drug resistance, and immune evasion.[20,21,22,23] Noninvasive methods and potential biomarkers are essential for early detection. The results implied that exosomal CYPA could become a promising biomarker for EBV‐associated NPC
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