Potential of Pre-Operative Serum Interleukin-6 as a Biomarker for Colorectal Cancers
DOI:
https://doi.org/10.30683/1929-2279.2024.13.05Keywords:
Colorectal cancer, Interleukin-6, Interleukin-10, Carcinoembryonic antigen, Biomarker, DiagnosisAbstract
The diagnosis of colorectal cancers (CRC) at its early stage is challenging due to lack of early markers. Current diagnostic tests are either invasive or show low sensitivity. Interleukins are known to elevate and play important roles in the development and progression of the CRC. The studies on interleukin profiles of CRC patients are mainly confined to Caucasian populations while South Asian data are sparse. Therefore, the aim of this study was to investigate the serum IL-6 and IL-10 levels in a cohort of Sri Lankan CRC patients and explore their potential to be used as markers for early diagnosis/prognosis of CRC. Blood samples from 35 CRC patients and 35 healthy volunteers were obtained after informed consent. Their clinical findings and carcinoembryonic antigen (CEA) levels were recorded. Concentrations of IL-6 and IL-10 were measured using ELISA according to manufacturer’s protocols.
Mean serum [IL-6] was found to be significantly higher in CRC patients than controls (p<0.05). The mean [IL-10]showed no difference to that of controls. (p>0.05). Interestingly, the [IL-6] in CRC patients were correlated with the disease stage (Stage I-0.16pg/ml; stage II-7.01pg/ml; stage III-15.8pg/ml and stage IV-35.48pg/ml). CEA levels were not correlated with the disease stage or withIL-6 levels. This study provided preliminary evidence to use IL-6 as a potential biochemical marker for the diagnosis of CRC inaddition to CEA. Furthermore, IL-6 could be a marker for prognosis of CRC. Further studies with higher patient samples are needed to validate the results of this study.
References
Pourhoseingholi MA. Increased burden of colorectal cancer in Asia. World J Gastrointest Oncol 2012; 4: 68-70. https://doi.org/10.4251/wjgo.v4.i4.68
Huang J, Ngai CH, Deng Y, et al. Cancer incidence and mortality in Asian countries: A trend analysis. Cancer Control 2022; 29: 10732748221095955. https://doi.org/10.1177/10732748221095955
Rajappa S, Singh M, Uehara R, et al. Cancer incidence and mortality trends in Asia based on regions and human development index levels: an analyses from GLOBOCAN 2020. Curr Med Res Opin 2023; 39: 1127-1137. https://doi.org/10.1080/03007995.2023.2231761
Bond JH. Fecal occult blood test screening for colorectal cancer. Gastrointest Endosc Clin N Am 2002; 12: 11-21. https://doi.org/10.1016/s1052-5157(03)00054-0
Bond JH. Colorectal cancer screening: the potential role of virtual colonoscopy. J Gastroenterol 2002; 37(Suppl 13): 92-96. https://doi.org/10.1007/BF02990108
Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin 2008; 58: 130 -160. https://doi.org/10.3322/CA.2007.0018
Belluco C, Nitti D, Frantz M, et al. Interleukin-6 blood level is associated with circulating carcinoembryonic antigen and prognosis in patients with colorectal cancer. Ann Surg Oncol 2000; 7: 133-8. https://doi.org/10.1007/s10434-000-0133-7
Thirunavukarasu P, Talati C, Munjal S, et al. Effect of incorporation of pretreatment serum carcinoembryonic antigen evels into AJCC staging for colon cancer on 5-year survival. JAMA Surg 2015; 150: 747-755. https://doi.org/10.1001/jamasurg.2015.0871
Sajid KM, Parveen R, Durr-e-Sabih, et al. Carcinoembryonic antigen (CEA) levels in hookah smokers, cigarette smokers and non-smokers. J Pak Med Assoc 2007; 57: 595-9.
Nicholson BD, Shinkins B, Pathiraja I, et al. Blood CEA levels for detecting recurrent colorectal cancer. Cochrane Database Syst Rev 2015; (12): CD011134. https://doi.org/10.1002/14651858.CD011134.pub2
Katoh H, Yamashita K, Kokuba Y, et al. Diminishing impact of preoperative carcinoembryonic antigen (CEA) in prognosis of Dukes' C colorectal cancer. Anticancer Res 2008; 28(3B): 1933-41.
Nadji M. Tumor markers in gynecologic neoplasms. Clin Lab Med 1990; 10: 105-17.
Grunnet M, Sorensen JB. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung Cancer 2012; 76: 138-43. https://doi.org/10.1016/j.lungcan.2011.11.012
Asad-Ur-Rahman F, Saif MW, et al. Elevated level of serum carcinoembryonic antigen (CEA) and search for a malignancy: A case report Cureus 2016; 8(6): e648. https://doi.org/10.7759/cureus.648
Waldner MJ, Foersch S, Neurath MF, et al. Interleukin-6: a key regulator of colorectal cancer development. Int J Biol Sci 2012; 8: 1248-53. https://doi.org/10.7150/ijbs.4614
Komoda H, Tanaka Y, Honda M, et al. Interleukin-6 levels in colorectal cancer tissues. World J Surg 1998; 22: 895-8. https://doi.org/101007/s002689900489
Maihöfner C, Charalambous MP, Bhambra U, et al. Expression of cyclooxygenase-2 parallels expression of interleukin-1beta, interleukin-6 and NF-kappaB in human colorectal cancer. Carcinogenesis 2003; 24: 665-71. https://doi.org/10.1093/carcin/bgg006
Eldesoky A, Shouma A, Mosaad Y, et al. Clinical relevance of serum vascular endothelial growth factor and interleukin-6 in patients with colorectal cancer. Saudi J Gastroenterol 2011; 17: 170-3. https://doi.org/10.4103/1319-3767.80378
Corvinus FM, Orth C, Moriggl R, et al. Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth. Neoplasia 2005; 7: 545-55. https://doi.org/10.1593/neo.04571
Lin Y, He Z, Ye J, et al. Progress in Understanding the IL-6/STAT3 Pathway in Colorectal Cancer. Onco Targets Ther 2010; 13: 13023-13032. https://doi.org/10.2147/OTT.S278013
Grivennikov S, Karin E, Terzic J, et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 2009; 15: 103-13. https://doi.org/10.1016/j.ccr.2009.01.001
Florescu DN, Boldeanu MV, Șerban RE, et al. Correlation of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, inflammatory markers, and tumor markers with the diagnosis and prognosis of colorectal cancer. Life (Basel) 2023; 13: 2261. https://doi.org/10.3390/life13122261
Li B, Wang F, Ma C, et al. Predictive value of IL-18 and IL-10 in the prognosis of patients with colorectal cancer. Oncology letters 2019; 18: 713-719. https://doi.org/10.3892/ol.2019.10338
O'Hara RJ, Greenman J, MacDonald AW, et al. Advanced colorectal cancer is associated with impaired interleukin 12 and enhanced interleukin 10 production. Clin Cancer Res 1998; 4: 1943-8.
Stanilov N, Miteva L, Deliysky T, et al. Advanced colorectal cancer is associated with enhanced IL-23 and IL-10 serum levels. Lab Med 2010; 41(3): 159-63. https://doi.org/10.1309/LM7T43AQZIUPIOWZ
World Medical Association. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bull World Health Organ. 2001; 79: 373-4.
Shiga K, Hara M, Nagasaki T, et al. Preoperative serum interleukin-6 is a potential prognostic factor for colorectal cancer, including Stage II patients. Gastroenterol Res Pract 2016: 9701574. https://doi.org/10.1155/2016/9701574
Komoda H, Tanaka Y, Honda M, et al. Matsuo Y, Hazama K, Takao T. Interleukin-6 levels in colorectal cancer tissues. World J Surg 1998; 22: 895-8.
Chung YC, Chang YF. Serum interleukin-6 levels reflect the disease status of colorectal cancer. J SurgOncol 2003; 83: 222-6. https://doi.org/10.1002/jso.10269
Galizia G, Orditura M, Romano C, et al. Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery. ClinImmunol 2002; 102: 169-78. https://doi.org/10.1006/clim.2001.5163
Rohini S, Manuela Z, Stephen J, et al Systemic inflammatory response predicts prognosis in patients with advanced-stage. CIG Journal 2008; 7: 331-37. https://doi.org/10.3816/CCC.2008.n.044
Kaminska J, Kowalska MM, Nowacki MP, et al. CRP, TNF-α, IL-1ra, IL-6 and IL-10 in blood serum of CRC patients. PatholOncol-Res 2000; 6: 38-41. https://doi.org/10.1007/BF03032656
Belluco C, Nitti D, Frantz M, et al. Interleukin-6 blood level is associated with circulating carcinoembryonic antigen and prognosis in patients with colorectal cancer. Ann Surg Oncol 2000; 7: 133-8. https://doi.org/10.1007/s10434-000-0133-7
Topdagi O and Timuroglu A. Evaluation of the relationship between carcinoembryonic antigen and TNM stage in colorectal cancer. Eurasian J Med 2018; 50: 96-98. https://doi.org/10.5152/eurasianjmed.2018.17093
Lin JK, Lin CC, Yang SH. Early postoperative CEA level is a better prognostic indicator than is preoperative CEA level in predicting prognosis of patients with curable colorectal cancer. Int J Colorectal Dis 2011; 26: 1135-41. https://doi.org/10.1007/s00384-011-1209-5
Guthrie GJ, Roxburgh CS, Richards CH, et al. Circulating IL-6 concentrations link tumour necrosis and systemic and local inflammatory responses in patients undergoing resection for colorectal cancer. Br J Cancer 2013; 109: 131-7. https://doi.org/10.1038/bjc.2013.291
Goydos JS, Brumfield AM, Frezza E, et al. Marked elevation of serum interleukin-6 in patients withcholangiocarcinoma: validation of utility as a clinical marker. Ann Surg 1998; 227: 398-404. https://doi.org/10.1097/00000658-199803000-00012
Jeong SY, Jeon BG, Kim JE, et al. Interleukin 10 level in the peritoneal cavity is a prognostic marker for peritoneal recurrence of T4 colorectal cancer. Sci Rep 2011; 11: 9212. https://doi.org/10.1038/s41598-021-88653-2
Abtahi S, Davani F, Mojtahedi Z, et al. Dual association of serum interleukin-10 levels with colorectal cancer. J Cancer Res Ther 2017; 13: 252-256. https://doi.org/10.4103/0973-1482.199448
Szkaradkiewicz A, Marciniak R, Chudzicka-Strugała I, et al. Proinflammatory cytokines and IL-10 in inflammatory bowel disease and colorectal cancer patients. Arch Immunol Ther Exp (Warsz) 2009; 57: 291-4. https://doi.org/10.1007/s00005-009-0031-z
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