Isthmin-1, meteorin-like, and neuregulin-4 as potential diagnostic novel biomarkers for colorectal cancer in Thi-Qar Governorate, Iraq

Abstract Colorectal cancer (CRC) is one of the leading causes of cancer complications and deaths globally. Unfortunately, we have limited tests for early diagnosis of the disease. Nevertheless, novel integrative metabolic and inflammatory markers, including Isthmin-1 (ISM1), Meteorin-like (Metrnl), Neuregulin-4 (NRG4), which have the ability to formulate novel diagnostic strategies and broaden the knowledge of CRC. In a case-control study of 180 individuals, three groups were assessed: patients with CRC, individuals with benign colorectal disease (BCD), and healthy controls (HC), with 60 individuals in each category. ELISA was performed to assess the levels of these markers in individuals’ blood. Statistical results showed clearly higher ISM1 levels in CRC patients (8.91 ± 2.14 ng/mL); BCD and HC showed 5.76 ± 1.63 ng/mL and 4.83 ± 1.41 ng/mL, respectively (p < 0.001). Metrnl values were lowered by 62.8 ± 15.7 pg/mL in CRC patients, versus 88.5 ± 19.4 pg/mL in BCD and 96.3 ± 20.1 pg/mL in HC (p < 0.001). NRG4 values were equally low in CRC patients, averaging 1.74 ± 0.52 ng/mL, although this was lower than in HC (p < 0.001). The ROC analysis was promising for the three markers, with AUC of 0.912 for ISM1, 0.895 for Metrnl, and 0.887 for NRG4. In addition, ISM1 was positively associated with tumor stage and tumor size (r = 0.61, 0.53), yet Metrnl and NRG4 had the opposite effect. This study demonstrates that elevated ISM1 levels, in conjunction with decreased Metrnl and NRG4 levels, are significantly associated with CRC and its severity. These biomarkers provide more accurate predictions, which may contribute to enhancing our understanding of early CRC detection and identifying risk factors.