Is Interluekin-6 (IL-6) an Appropriate Diagnostic and Prognostic Biomarker for Colorectal Cancers?

• W.M.M.S. Bandara

  Department of Pre –Clinical Sciences, General Sir John Kotelawala Defence University Rathmalana, Sri Lanka

• A.J.I.S. Rathnayake

  Department of Pre –Clinical Sciences, General Sir John Kotelawala Defence University Rathmalana, Sri Lanka

Development of colorectal cancer (CRC) is a slow process, where a benign polyp progresses into a malignant stage over a long period of time. The patient may be asymptomatic during this period, thus delayed diagnosis has become a prime obstacle in managing CRC. Improved routine screening for early detection and prognosis will aid in better management of CRCs reducing mortality rates.

Diagnosis of CRCs is primarily based on the invasive colonoscopy and tissue biopsy and fecal occult blood test with alongside evaluation of carcinoembryonic antigen (CEA) levels in blood for prognosis and recurrence. However, CEA as a standalone biomarker for CRCs, fail due to its non-specificity, low sensitivity and high false-positivity highlighting the importance of identification of new biomarkers for CRCs.

In the recent past inflammatory cytokines emerged as key drivers of CRC pathogenesis, particularly as determinants of disease progression. The pleiotropic cytokine, interleukin-6 (IL-6) has been identified as activating oncogenic gene transcription in the colorectal epithelial cells leading to the pathogenesis of CRCs. By activating STAT3 signaling pathway, IL-6 promotes initiation, growth and metastasis of the colorectal cancer cell clone. In this review, we present the prospect of IL-6 in CRCs, describing the emerging evidence for IL-6 as a potential biomarker, the drawbacks of IL-6 and future directions for IL-6 as a diagnostic and prognostic marker for CRC.

The original articles were extracted from the PubMed using the key words: "IL-6/interleukin 6 levels in colorectal cancer/ IL-6/ interleukin 6 concentrations in colorectal cancer/ IL-6 expression/ serum interleukin 6/ IL-6 in colorectal cancer". Full text articles published in English in last 25 years (from 2000 to July 2025) were included and the research carried out in animal models and in vitro, reviews, case reports, meta-analyses, editorials and non-relevant articles (post –surgery/treatment, studies on IL-6 in overlapping cancers/conditions etc.) were excluded.

Though IL-6 stands as a potential marker for CRCs with markedly elevated levels, heterogeneity of patient populations with inadequacy of data for defining and distinguishing clinical sub groups, control groups and methodologies have become a barrier for its progression from bench to bed side. Hence, prospective research need to be focused on obtaining data on IL-6 using standardized methodologies to determine stage-specific and population specific cut-off values in well-defined CRC sub groups.

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