Download PDF
CC BY-NC-ND 4.0 · J Lab Physicians
DOI: 10.1055/s-0043-1772772
Original Article

Serum Levels of Interleukin-6 and Tumor Necrosis Factor-Alpha in Diagnosis and Prognosis of Gallbladder Cancer: A Pilot Study

Poonam Sharma   *
1   Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
,
Sarath Krishnan M P   *
1   Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
,
Amit Gupta
2   Department of General Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
,
Sweety Gupta
3   Department of Radiation Oncology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
,
Rahul Saxena
1   Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
,
Anissa Atif Mirza
1   Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
,
Bela Goyal
1   Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
› Author Affiliations Funding None.
› Further Information
   Permissions and Reprints

Abstract

Objectives Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) are proinflammatory cytokines that play a major role in tumorigenesis. These biomarkers are relatively unexplored in gallbladder cancer (GBC) for their diagnostic and prognostic utility.

Material and Methods A total of 40 healthy controls and 40 GBC patients were recruited. Serum IL-6 and TNF-α levels were measured, and their diagnostic utility was analyzed using the receiver operating characteristics (ROC) curve. The relationship between clinicopathological variables and serum tumor markers (CEA, CA125, and CA19-9) in identifying GBC patients was also assessed.

Results Serum IL-6 and TNF-α expression were significantly higher in the GBC group (for both IL-6 and TNF-α, p = 0.0001) than in healthy controls. ROC analysis revealed that the areas under the curve for serum IL-6 and TNF-α were 0.89 and 0.71, respectively. The sensitivity and specificity for serum IL-6 were 82.5 and 97.5%, respectively, at an optimal cutoff value of 10.34 pg/mL; for TNF-α, they were 40.0 and 100%, respectively, at a cutoff value of 0.24 pg/mL. There was also a significant difference in serum IL-6 levels between the resectable and nonresectable GBC groups. Serum IL-6 showed a positive correlation with CA125 (r = 0.34, p < 0.05), while no correlation was observed between serum TNF-α and serum tumor markers (CEA, CA125, and CA19-9).

Conclusion Serum IL-6 may serve as a diagnostic marker and a predictor of resectability, and it can be used in conjunction with other serum tumor markers in GBC.

Keywords

gallbladder cancer - interleukin-6 - tumor necrosis factor-alpha

Ethical Approval and Consent to Participate

Ethical approval was given by the All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India, under reference number 422/IEC/M. Sc/2020.


* Co-first authors.




Publication History

Article published online:
24 August 2023

© 2023. The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Recio Boiles A, Kashyap S, Babiker HM. Gallbladder Cancer. Treasure Island, FL: Stat Pearls Publishing; 2021
    Google Scholar
  • 2 Globocan 2020. The Global Cancer Observatory. November, 2020 , Available at: https://gco.iarc.fr/
    PubMed
  • 3 Nandakumar A, Gupta PC, Gangadharan P, Visweswara RN, Parkin DM. Geographic pathology revisited: development of an atlas of cancer in India. Int J Cancer 2005; 116 (05) 740-754
    CrossrefPubMedGoogle Scholar
  • 4 Sharma A, Sharma KL, Gupta A, Yadav A, Kumar A. Gallbladder cancer epidemiology, pathogenesis and molecular genetics: recent update. World J Gastroenterol 2017; 23 (22) 3978-3998
    CrossrefPubMedGoogle Scholar
  • 5 Sheth S, Bedford A, Chopra S. Primary gallbladder cancer: recognition of risk factors and the role of prophylactic cholecystectomy. Am J Gastroenterol 2000; 95 (06) 1402-1410
    CrossrefPubMedGoogle Scholar
  • 6 Chung SS, Wu Y, Okobi Q. et al. Proinflammatory cytokines IL-6 and TNF-α increased telomerase activity through NF-κB/STAT1/STAT3 activation, and withaferin A inhibited the signaling in colorectal cancer cells. Mediators Inflamm 2017; 2017: 5958429
    CrossrefPubMedGoogle Scholar
  • 7 Michalaki V, Syrigos K, Charles P, Waxman J. Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features and patient survival in patients with prostate cancer. Br J Cancer 2004; 90 (12) 2312-2316
    CrossrefPubMedGoogle Scholar
  • 8 Chang CH, Hsiao CF, Yeh YM. et al. Circulating interleukin-6 level is a prognostic marker for survival in advanced nonsmall cell lung cancer patients treated with chemotherapy. Int J Cancer 2013; 132 (09) 1977-1985
    CrossrefPubMedGoogle Scholar
  • 9 Masjedi A, Hashemi V, Hojjat-Farsangi M. et al. The significant role of interleukin-6 and its signaling pathway in the immunopathogenesis and treatment of breast cancer. Biomed Pharmacother 2018; 108: 1415-1424
    CrossrefPubMedGoogle Scholar
  • 10 Macciò A, Madeddu C. The role of interleukin-6 in the evolution of ovarian cancer: clinical and prognostic implications: a review. J Mol Med (Berl) 2013; 91 (12) 1355-1368
    CrossrefPubMedGoogle Scholar
  • 11 Liu Z, Kemp TJ, Gao YT. et al. Author correction: circulating levels of inflammatory proteins and survival in patients with gallbladder cancer. Sci Rep 2020; 10 (01) 2680
    CrossrefPubMedGoogle Scholar
  • 12 Høgdall D, O'Rourke CJ, Dehlendorff C. et al. Serum IL6 as a prognostic biomarker and IL6R as a therapeutic target in biliary tract cancers. Clin Cancer Res 2020; 26 (21) 5655-5667
    CrossrefPubMedGoogle Scholar
  • 13 Wang X, Lin Y. Tumor necrosis factor and cancer, buddies or foes?. Acta Pharmacol Sin 2008; 29 (11) 1275-1288
    CrossrefPubMedGoogle Scholar
  • 14 Du Q, Jiang L, Wang X, Wang M, She F, Chen Y. Tumor necrosis factor-α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor-κB-mediated upregulation of vascular endothelial growth factor-C. Cancer Sci 2014; 105 (10) 1261-1271
    CrossrefPubMedGoogle Scholar
  • 15 Hong H, Jiang L, Lin Y. et al. TNF-alpha promotes lymphangiogenesis and lymphatic metastasis of gallbladder cancer through the ERK1/2/AP-1/VEGF-D pathway. BMC Cancer 2016; 16: 240
    CrossrefPubMedGoogle Scholar
  • 16 Chaturmohta A, Dixit R, Narayan G. et al. Do expression profiles of cytokines VEGF, TNF-α, IL-1β, IL-6 and IL-8 correlate with gallbladder cancer. Journal of Cancer Science and Clinical Oncology. 2015; 2: 2
    Google Scholar
  • 17 Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res 2014; 2014: 149185
    CrossrefPubMedGoogle Scholar
  • 18 Popa C, Netea MG, van Riel PLCM, van der Meer JWM, Stalenhoef AFH. The role of TNF-α in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res 2007; 48 (04) 751-762
    CrossrefPubMedGoogle Scholar
  • 19 Heikkilä K, Ebrahim S, Lawlor DA. Systematic review of the association between circulating interleukin-6 (IL-6) and cancer. Eur J Cancer 2008; 44 (07) 937-945
    CrossrefPubMedGoogle Scholar
  • 20 Li Y, Zhang J, Ma H. Chronic inflammation and gallbladder cancer. Cancer Lett 2014; 345 (02) 242-248
    CrossrefPubMedGoogle Scholar
  • 21 Xu J, Ye Y, Zhang H. et al. Diagnostic and prognostic value of serum interleukin-6 in colorectal cancer. Medicine (Baltimore) 2016; 95 (02) e2502
    CrossrefPubMedGoogle Scholar
  • 22 Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420 (6917): 860-867
    CrossrefPubMedGoogle Scholar
  • 23 Rajput M. et al. The relationship between serum levels of CA- 125 and interleukin-6 with the degree of differentiation in ovarian neoplasms. Annals of Pathology and Laboratory Medicine. 2019; 6 (07) 392-397
    CrossrefGoogle Scholar