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Albumin, Globulin, and Albumin-Globulin Ratio with EBV DNA as Potential Markers for Nasopharyngeal Carcinoma: Experience from a Regional Cancer Centre in North-Eastern India

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Healthcare Research and Related Technologies (NERC 2022)

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Abstract

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy in the north-eastern region of India. Epstein Barr virus (EBV) infection coupled with inflammation and nutritional status has a significant effect on NPC diagnosis. Recent studies have cited albumin, globulin levels and albumin/globulin ratio as predictive factors in various cancer types. We evaluate the potential value of EBV DNA, serum albumin, globulin, and AGR and their correlation to NPC diagnosis in this region. EBV load was assessed by quantitative PCR (qPCR) assay in 105 biopsy-proven NPC patients and 115 matched healthy participants. Further serum profiles were measured by Capillary Electrophoresis and the AGR value was determined. The effectiveness of EBV-DNA, serum albumin, globulin, and AGR was examined, and its diagnostic performance was calculated. Our results demonstrated higher EBV DNA copies tend to be associated with the risk of NPC. EBV DNA load was found higher in advanced-stage than those in early-stage patients (p < 0.05). The receiver operating characteristic curve shows EBV DNA levels with a sensitivity of 81.4% and specificity of 91.43% with cut-off values of 3893 copies/ml for distinguishing NPC patients from healthy donors. In addition, low serum albumin and low AGR with high globulin levels were also significantly correlated with NPC with optimal cut-off values of ≤4.06 g/dL, ≤1, and >3.59 g/dL respectively. In summary, the combination of AGR with albumin and globulin and EBV load were associated with the development of NPC and can serve as promising biomarkers in the clinical management of NPC.

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References

  1. Chang ET, Adami HO (2006) The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 15(10):1765–1777. https://doi.org/10.1158/1055-9965.Epi-06-0353

    Article  Google Scholar 

  2. Forman D (2014) Cancer incidence in five continents: volume X. International Agency for Research on Cancer

    Google Scholar 

  3. Kataki AC, Simons MJ, Das AK, Sharma K, Mehra NK (2011) Nasopharyngeal carcinoma in the Northeastern states of India. Chin J Cancer 30(2):106–113. https://doi.org/10.5732/cjc.010.10607

    Article  Google Scholar 

  4. Sharma TD, Singh TT, Laishram RS, Sharma LD, Sunita AK, Imchen LT (2011) Nasopharyngeal carcinoma–a clinico-pathological study in a regional cancer centre of northeastern India. Asian Pac J Cancer Prev: APJCP 12(6):1583–1587

    Google Scholar 

  5. Lung ML, Cheung AK, Ko JM, Lung HL, Cheng Y, Dai W (2014) The interplay of host genetic factors and Epstein-Barr virus in the development of nasopharyngeal carcinoma. Chin J Cancer 33(11):556–568. https://doi.org/10.5732/cjc.014.10170

    Article  Google Scholar 

  6. Lakhanpal M, Singh LC, Rahman T, Sharma J, Singh MM, Kataki AC et al (2015) Contribution of susceptibility locus at HLA class I region and environmental factors to occurrence of nasopharyngeal cancer in Northeast India. Tumour Biol 36(4):3061–3073. https://doi.org/10.1007/s13277-014-2942-5

    Article  Google Scholar 

  7. Hau PM, Lung HL, Wu M, Tsang CM, Wong KL, Mak NK et al (2020) Targeting Epstein-Barr virus in nasopharyngeal carcinoma. Front Oncol 10:600. https://doi.org/10.3389/fonc.2020.00600

    Article  Google Scholar 

  8. Ng WT, Yuen KT, Au KH, Chan OS, Lee AW (2014) Staging of nasopharyngeal carcinoma–the past, the present and the future. Oral Oncol 50(6):549–554. https://doi.org/10.1016/j.oraloncology.2013.06.003

    Article  Google Scholar 

  9. Li HP, Hsu CL, Chang YS (2018) Screening of nasopharyngeal carcinoma using plasma Epstein-Barr virus DNA for at-risk population. 2:3

    Google Scholar 

  10. Kimura H, Kwong YL (2019) EBV viral loads in diagnosis, monitoring, and response assessment. Front Oncol 9:62. https://doi.org/10.3389/fonc.2019.00062

    Article  Google Scholar 

  11. Tan R, Phua SKA, Soong YL, Oon LLE, Chan KS, Lucky SS et al (2020) Clinical utility of Epstein-Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma. Cancer Commun (London, England) 40(11):564–585. https://doi.org/10.1002/cac2.12100

    Article  Google Scholar 

  12. McMillan DC (2009) Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care 12(3):223–226. https://doi.org/10.1097/MCO.0b013e32832a7902

    Article  Google Scholar 

  13. Laviano A, Koverech A, Mari A (2015) Cachexia: clinical features when inflammation drives malnutrition. Proc Nutr Soc 74(4):348–354. https://doi.org/10.1017/s0029665115000117

    Article  Google Scholar 

  14. Lu H, Ouyang W, Huang C (2006) Inflammation, a key event in cancer development. Mol Cancer Res: MCR 4(4):221–233. https://doi.org/10.1158/1541-7786.Mcr-05-0261

    Article  Google Scholar 

  15. Du XJ, Tang LL, Mao YP, Sun Y, Zeng MS, Kang TB et al (2014) The pretreatment albumin to globulin ratio has predictive value for long-term mortality in nasopharyngeal carcinoma. PLoS ONE 9(4):e94473. https://doi.org/10.1371/journal.pone.0094473

    Article  Google Scholar 

  16. Willegger M, Posch F, Schieder S, Funovics PT, Scharrer A, Brodowicz T et al (2017) Serum creatinine and albumin predict sarcoma-specific survival in patients with myofibroblastic and fibroblastic sarcomas. J Orthop Res 35(12):2815–2824. https://doi.org/10.1002/jor.23598

    Article  Google Scholar 

  17. Ichikawa K, Mizuno S, Hayasaki A, Kishiwada M, Fujii T, Iizawa Y et al (2019) Prognostic nutritional index after chemoradiotherapy was the strongest prognostic predictor among biological and conditional factors in localized pancreatic ductal adenocarcinoma patients. Cancers (Basel) 11(4). https://doi.org/10.3390/cancers11040514

  18. Meyer EJ, Nenke MA, Rankin W, Lewis JG, Torpy DJ (2016) Corticosteroid-binding globulin: a review of basic and clinical advances. Horm Metab Res 48(6):359–371. https://doi.org/10.1055/s-0042-108071

    Article  Google Scholar 

  19. Gupta D, Lis CG (2010) Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J 9:69. https://doi.org/10.1186/1475-2891-9-69

    Article  Google Scholar 

  20. Jin Y, Zhao L, Peng F (2013) Prognostic impact of serum albumin levels on the recurrence of stage I non-small cell lung cancer. Clinics (Sao Paulo, Brazil) 68(5):686–693. https://doi.org/10.6061/clinics/2013(05)17

    Article  Google Scholar 

  21. Li G, Gao J, Liu ZG, Tao YL, Xu BQ, Tu ZW et al (2014) Influence of pretreatment ideal body weight percentile and albumin on prognosis of nasopharyngeal carcinoma: long-term outcomes of 512 patients from a single institution. Head Neck 36(5):660–666. https://doi.org/10.1002/hed.23357

    Article  Google Scholar 

  22. Adly L, Hill D, Sherman ME, Sturgeon SR, Fears T, Mies C et al (2006) Serum concentrations of estrogens, sex hormone-binding globulin, and androgens and risk of breast cancer in postmenopausal women. Int J Cancer 119(10):2402–2407. https://doi.org/10.1002/ijc.22203

    Article  Google Scholar 

  23. Asher V, Lee J, Bali A (2012) Preoperative serum albumin is an independent prognostic predictor of survival in ovarian cancer. Med Oncol 29(3):2005–2009. https://doi.org/10.1007/s12032-011-0019-5

    Article  Google Scholar 

  24. Guthrie GJ, Roxburgh CS, Farhan-Alanie OM, Horgan PG, McMillan DC (2013) Comparison of the prognostic value of longitudinal measurements of systemic inflammation in patients undergoing curative resection of colorectal cancer. Br J Cancer 109(1):24–28. https://doi.org/10.1038/bjc.2013.330

  25. Azab BN, Bhatt VR, Vonfrolio S, Bachir R, Rubinshteyn V, Alkaied H et al (2013) Value of the pretreatment albumin to globulin ratio in predicting long-term mortality in breast cancer patients. Am J Surg 206(5):764–770. https://doi.org/10.1016/j.amjsurg.2013.03.007

    Article  Google Scholar 

  26. Yao Y, Zhao M, Yuan D, Gu X, Liu H, Song Y (2014) Elevated pretreatment serum globulin albumin ratio predicts poor prognosis for advanced non-small cell lung cancer patients. J Thorac Dis 6(9):1261–1270. https://doi.org/10.3978/j.issn.2072-1439.2014.07.13

    Article  Google Scholar 

  27. Shibutani M, Maeda K, Nagahara H, Ohtani H, Iseki Y, Ikeya T et al (2015) The pretreatment albumin to globulin ratio predicts chemotherapeutic outcomes in patients with unresectable metastatic colorectal cancer. BMC Cancer 15:347. https://doi.org/10.1186/s12885-015-1375-x

    Article  Google Scholar 

  28. Lv GY, An L, Sun XD, Hu YL, Sun DW (2018) Pretreatment albumin to globulin ratio can serve as a prognostic marker in human cancers: a meta-analysis. Clin Chim Acta 476:81–91. https://doi.org/10.1016/j.cca.2017.11.019

    Article  Google Scholar 

  29. Puri KS, Suresh KR, Gogtay NJ, Thatte UM (2009) Declaration of Helsinki, 2008: implications for stakeholders in research. J Postgrad Med 55(2):131–134. https://doi.org/10.4103/0022-3859.52846

    Article  Google Scholar 

  30. Edge SB, Compton CC (2010) The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17(6):1471–1474. https://doi.org/10.1245/s10434-010-0985-4

  31. Tune CE, Liavaag PG, Freeman JL, van den Brekel MW, Shpitzer T, Kerrebijn JD et al (1999) Nasopharyngeal brush biopsies and detection of nasopharyngeal cancer in a high-risk population. J Natl Cancer Inst 91(9):796–800. https://doi.org/10.1093/jnci/91.9.796

    Article  Google Scholar 

  32. Nonoyama M, Pagano JS (1973) Homology between Epstein-Barr virus DNA and viral DNA from Burkitt’s lymphoma and nasopharyngeal carcinoma determined by DNA-DNA reassociation kinetics. Nature 242(5392):44–47. https://doi.org/10.1038/242044a0

    Article  Google Scholar 

  33. Lourembam DS, Singh AR, Sharma TD, Singh TS, Singh TR, Singh LS (2015) Evaluation of risk factors for nasopharyngeal carcinoma in a high-risk area of India, the Northeastern Region. Asian Pac J Cancer Prev: APJCP 16(12):4927–4935. https://doi.org/10.7314/apjcp.2015.16.12.4927

    Article  Google Scholar 

  34. Petersen JR, Okorodudu AO, Mohammad A, Payne DA (2003) Capillary electrophoresis and its application in the clinical laboratory. Clin Chim Acta 330(1–2):1–30. https://doi.org/10.1016/s0009-8981(03)00006-8

    Article  Google Scholar 

  35. Hoo ZH, Candlish J, Teare D (2017) What is an ROC curve? Emerg Med J: EMJ 34(6):357–359. https://doi.org/10.1136/emermed-2017-206735

    Article  Google Scholar 

  36. Mentzer AJ, Brenner N, Allen N, Littlejohns TJ, Chong AY, Cortes A et al (2022) Identification of host-pathogen-disease relationships using a scalable multiplex serology platform in UK Biobank. Nat Commun 13(1):1818. https://doi.org/10.1038/s41467-022-29307-3

    Article  Google Scholar 

  37. Adham M, Greijer AE, Verkuijlen SA, Juwana H, Fleig S, Rachmadi L et al (2013) Epstein-Barr virus DNA load in nasopharyngeal brushings and whole blood in nasopharyngeal carcinoma patients before and after treatment. Clin Cancer Res 19(8):2175–2186. https://doi.org/10.1158/1078-0432.Ccr-12-2897

    Article  Google Scholar 

  38. Yip TT, Ngan RK, Fong AH, Law SC (2014) Application of circulating plasma/serum EBV DNA in the clinical management of nasopharyngeal carcinoma. Oral Oncol 50(6):527–538. https://doi.org/10.1016/j.oraloncology.2013.12.011

    Article  Google Scholar 

  39. He SS, Wang Y, Bao Y, Cai XY, Yang XL, Chen DM et al (2018) Dynamic changes in plasma Epstein-Barr virus DNA load during treatment have prognostic value in nasopharyngeal carcinoma: a retrospective study. Cancer Med 7(4):1110–1117. https://doi.org/10.1002/cam4.1381

    Article  Google Scholar 

  40. Alfieri S, Iacovelli NA, Marceglia S, Lasorsa I, Resteghini C, Taverna F et al (2017) Circulating pre-treatment Epstein-Barr virus DNA as prognostic factor in locally-advanced nasopharyngeal cancer in a non-endemic area. Oncotarget 8(29):47780–47789. https://doi.org/10.18632/oncotarget.17822

    Article  Google Scholar 

  41. Mayne ST, Playdon MC, Rock CL (2016) Diet, nutrition, and cancer: past, present and future. Nat Rev Clin Oncol 13(8):504–515. https://doi.org/10.1038/nrclinonc.2016.24

    Article  Google Scholar 

  42. Ritter B, Greten FR (2019) Modulating inflammation for cancer therapy. J Exp Med 216(6):1234–1243. https://doi.org/10.1084/jem.20181739

    Article  Google Scholar 

  43. Luan CW, Tsai YT, Yang HY, Chen KY, Chen PH, Chou HH (2021) Pretreatment prognostic nutritional index as a prognostic marker in head and neck cancer: a systematic review and meta-analysis. Sci Rep 11(1):17117. https://doi.org/10.1038/s41598-021-96598-9

    Article  Google Scholar 

  44. Chi J, Xie Q, Jia J, Liu X, Sun J, Chen J et al (2018) Prognostic value of albumin/globulin ratio in survival and lymph node metastasis in patients with cancer: a systematic review and meta-analysis. J Cancer 9(13):2341–2348. https://doi.org/10.7150/jca.24889

    Article  Google Scholar 

  45. He J, Pan H, Liang W, Xiao D, Chen X, Guo M et al (2017) Prognostic effect of albumin-to-globulin ratio in patients with solid tumors: a systematic review and meta-analysis. J Cancer 8(19):4002–4010. https://doi.org/10.7150/jca.21141

    Article  Google Scholar 

  46. Rasouli M, Okhovatian A, Enderami A (2005) Serum proteins profile as an indicator of malignancy: multivariate logistic regression and ROC analyses. Clin Chem Lab Med 43(9):913–918. https://doi.org/10.1515/cclm.2005.156

    Article  Google Scholar 

  47. Yoshino Y, Taguchi A, Shimizuguchi T, Nakajima Y, Takao M, Kashiyama T et al (2019) A low albumin to globulin ratio with a high serum globulin level is a prognostic marker for poor survival in cervical cancer patients treated with radiation based therapy. Int J Gynecol Cancer 29(1):17–22. https://doi.org/10.1136/ijgc-2018-000025

    Article  Google Scholar 

  48. Selvyana D, Hutajulu SH, Kurnianda J (2017) The pretreatment albumin has a predictive value for overall survival in nasopharyngeal carcinoma. Ann Oncol 28:x108. https://doi.org/10.1093/annonc/mdx665.029

    Article  Google Scholar 

  49. Chen X, Long X, Liang Z, Lei H, Li L, Qu S et al (2017) Higher N stage and serum ferritin, but lower serum albumin levels are associated with distant metastasis and poor survival in patients with nasopharyngeal carcinoma following intensity-modulated radiotherapy. Oncotarget 8(42):73177–73186. https://doi.org/10.18632/oncotarget.17418

    Article  Google Scholar 

  50. Zhong LT, Wang H, Liang HQ, Su MR, Liu CD, Wu DH (2016) An elevated pretreatment serum globulin level predicts a poor prognosis of nasopharyngeal carcinoma. Nan Fang Yi Ke Da Xue Xue Bao 36(2):151–156

    Google Scholar 

  51. Du XJ, Tang LL, Mao YP, Guo R, Sun Y, Lin AH et al (2016) Circulating EBV DNA, globulin and nodal size predict distant metastasis after intensity-modulated radiotherapy in stage II Nasopharyngeal Carcinoma. J Cancer 7(6):664–670. https://doi.org/10.7150/jca.14183

    Article  Google Scholar 

  52. Azab B, Kedia S, Shah N, Vonfrolio S, Lu W, Naboush A et al (2013) The value of the pretreatment albumin/globulin ratio in predicting the long-term survival in colorectal cancer. Int J Colorectal Dis 28(12):1629–1636. https://doi.org/10.1007/s00384-013-1748-z

    Article  Google Scholar 

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Acknowledgements

We would like to thank the Director, RIMS, Imphal, and Dept of Biotechnology, Manipur University Imphal for supporting the conduct of this study, while the first author acknowledges RIMS, Imphal, India for financial assistance through DBT Grant. Govt. of India.

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Correspondence to Deepak Singh Lourembam .

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The study was approved [No: AC/112/EC/RIMS/2005/1481 dated 10th October 2011] by the Institutional Review Board (IRB), Regional Institute of Medical Sciences.

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All the authors declared no conflict of interest.

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Lourembam, D.S., Sharma, T.D., Singh, L.S. (2023). Albumin, Globulin, and Albumin-Globulin Ratio with EBV DNA as Potential Markers for Nasopharyngeal Carcinoma: Experience from a Regional Cancer Centre in North-Eastern India. In: Pandey, L.M., Gupta, R., Thummer, R.P., Kar, R.K. (eds) Healthcare Research and Related Technologies. NERC 2022. Springer, Singapore. https://doi.org/10.1007/978-981-99-4056-1_14

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