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The TNM staging system is currently used to detect cancer stages. Regardless, a small proportion of cancer patients recur even after therapy, suggesting more specific molecular tools are required to justify the stage-specific detection and prompt cancer diagnosis. Thus, we aimed to explore the blood-based DNA methylation signature of metastatic nasopharyngeal carcinoma (NPC) to establish a holistic methylation biomarker panel. For the identification of methylation signature, the EPIC BeadChip-based array was performed. Comparative analysis for identifying unique probes, validation, and functional studies was investigated by analyzing GEO and TCGA datasets. We observed 4093 differentially methylated probes (DMPs), 1232 hydroxymethylated probes, and 25 CpG islands. Gene expression study revealed both upregulated and downregulated genes. Correlation analysis suggested a positive (with a positive r, p ≤ 0.05) and negative (with a negative r, p ≤ 0.05) association with different cancers. TFBS analysis exhibited the binding site for many TFs. Furthermore, gene enrichment analysis indicated the involvement of those identified genes in biological pathways. However, blood-based DNA methylation data uncovered a distinct DNA methylation pattern, which might have an additive role in NPC progression by altering the TFs binding. Moreover, based on tissue-specificity, a variation of correlation between methylation and gene expression was noted in different cancers.

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RESUMEN

Nasopharyngeal Carcinoma (NPC) is one of the leading cancers in India's north-eastern (NE) region affecting a section of the population each year. A proportion of the NPC cases are observed to recur even after therapy, indicating the involvement of other factors. We aimed to explore the NPC and Epstein-Barr virus (EBV) burden in the NE region and investigate the prognostic factors for the NPC patients' poor survival and recurrence. NPC patients' information was obtained from different state hospitals between 2014 and 2019. PCR and Sanger sequencing were performed to detect EBV types. Statistical analysis, including forest plot analysis, Kaplan-Mayer survival plot, Log-rank test, cox hazard regression, and Aalen's additive regression model, were performed to determine prognostic factors for the NPC patients' lower survival and recurrence. We observed an increased incidence of NPC and EBV infection in the past five years. Step-wise statistical analyses pointed out that variable such as non-professionals (B = 1.02, HR = 2.8, 95%CI = 1.5,4.9) workers (B = 0.92, HR = 2.5, 95%CI = 1.4,4.4), kitchen cum bedroom (B = 0.61, HR = 1.8, 95%CI = 1.2,2.8), mosquito repellent (B = 0.60, HR = 1.7, 95%CI = 1.1,2.7), nasal congestion (B = 0.60, HR = 1.8, 95%CI = 1.2,2.8), lower haemoglobin level (B = 0.92, HR = 2.5, 95%CI = 1.3,4.9), tumor stage IV (B = 2.8, HR = 1.8, 95%CI = 1.6,14.3), N2 (B = 1.4, HR = 4.0, 95%CI = 1.8,9.1), N3 (B = 1.9, HR = 6.4, 95%CI = 2.8,15.3), and M+ (B = 2.02, HR = 7.5, 95%CI = 4.1,13.7) revealed significant correlation with NPC patients' poor prognosis (p < 0.05). The presence of viral factors also showed a significant association with NPC patients' decreased survival. We concluded that factors related to day-to-day life with EBV infection could be the individual predictor for NPC incidence, lower survival, and disease recurrence. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-022-00789-5.

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Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with viral malignancy, related to HIV-AIDS. With a wide geographical discrimination in its occurrence, Asian countries shows low to moderate prevalence with higher occurrence in some particular areas. India is one of the largest countries in Asia, having various geographical and cultural variations where KSHV has been considered as an unthinkable entity to cause any of its associated disease. India has been reported as a low prevalent zone for KSHV malignancy till date. Also there are no reports so far, describing the occurrence pattern of this malignancy. So this review approaches towards figuring out the tendency of prevalence pattern of this malignancy and associated risk factors found to be present in Indian population. From this study it is revealed that, KSHV related malignancy is a relatively newly reported and emerging disease in India and may exist in hidden pockets throughout India in association with tuberculosis. India shows prevalence in HIV-associated Kaposi's sarcoma in regions where socially discriminated LGBT (lesbian, gay, bisexual, and transgender) groups, unprotected sexual behavior and heterosexuality are the important risk factors for sexually transmitted viral diseases. Anti-retro viral therapy is not sufficient to combat the virus and may act adversely. On a note regarding the clinical representations of Kaposi's sarcoma, oral, mucosal, pleural and abdominal involvements are observed in worst cases and these can be considered as the main manifesting criteria for this malignancy among Indians.

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p53, p63, and p73, the members of the p53 family of proteins, are structurally similar proteins that play central roles regulating cell cycle and apoptotic cell death. Alternative splicing at the carboxyl terminus and the utilization of different promoters further categorizes these proteins as having different isoforms for each. Among such isoforms, TA and ΔN versions of each protein serve as the pro and the anti-apoptotic proteins, respectively. Changes in the expression patterns of these isoforms are noted in many human cancers. Proteins of certain human herpesviruses, like Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), interact with p53 family members and alter their expressions in many malignancies. Upon infections in the B cells and epithelial cells, EBV expresses different lytic or latent proteins during viral replication and latency respectively to preserve viral copy number, chromosomal integrity and viral persistence inside the host. In this review, we have surveyed and summarised the interactions of EBV gene products, known so far, with the p53 family proteins. The interactions between P53 and EBV oncoproteins are observed in stomach cancer, non-Hodgkin's lymphoma (NHL) of the head and neck, Nasopharyngeal Cancer (NPC), Gastric carcinoma (GC) and Burkitt's lymphoma (BL). EBV latent protein EBNA1, EBNA3C, LMP-1, and lytic proteins BZLF-1 can alter p53 expressions in many cancer cell lines. Interactions of p63 with EBNA-1, 2, 5, LMP-2A and BARF-1 have also been investigated in several cancers. Similarly, associations of p73 isoform with EBV latent proteins EBNA3C and LMP-1 have been reported. Methylation and single nucleotide polymorphisms in p53 have also been found to be correlated with EBV infection. Therefore, interactions and altered expression strategies of the isoforms of p53 family proteins in EBV associated cancers propose an important field for further molecular research.

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Parvovirus B-19, a single human pathogenic member of the Parvoviridae family with it's small ssDNA and non-enveloped structure, is known to cause diseases in erythroid progenitor cells. But a wide range of clinical association of this virus with cells of non-erythroid origins has recently been discovered and many of those are being investigated for such association. Higher substitution rates in due course of evolution has been suggested for this cellular tropism and persistence. In this report, we have summarized the different disease manifestations of B-19 virus and have tried to find out a pattern of pathogenesis. Finally, we have focused on the vaccination strategies available against B-19 virus to correlate these with the mechanisms involved in various diseases caused by this virus.