High proportion of circulating CD38+ NK cells：a novel biomarker for lymph node metastasis and poor prognosis in colorectal cancer

Abstract Background lymph node status is a critical prognostic factor for colorectal cancer (CRC). Due to the potential influence of immune system on CRC progression, investigation into lymphocyte subsets as clinical biomarkers has gained attention. The objective of this study was to assess the predictive capability of lymphocyte subsets for lymph node metastasis (LNM) and prognosis of CRC. Methods Lymphocyte subsets, including T cells (CD3+), natural killer cells (NK, CD3- CD56+), natural killer-like T cells (NKT-like, CD3 + CD56+), CD38 + NK cells (CD3- CD56 + CD38+) and CD38 + NKT-like cells (CD3 + CD56 + CD38+), were detected by flow cytometry. Univariate and multivariate analyses were used to assess the risk factors of LNM. The prognostic role of parameters was evaluated by survival analysis. Results The proportion of CD38 + NK cells within the NK cell population was significantly higher in LNM-positive patients ( p < 0.001). However, no significant differences were observed in the proportions of other lymphocyte subsets. Poorer histologic grade (odds ratio [OR] = 3.78, p = 0.039), lymphovascular invasion (LVI) (OR = 24.52, p < 0.001), and CD38 + NK cells (high) (OR = 4.67, p < 0.001) were identified as independent risk factors for LNM. Furthermore, high proportion of CD38 + NK cells was associated with poor prognosis of CRC patients (HR = 2.37, p = 0.025). Conclusions The proportion of CD38 + NK cells within the NK cell population is a promising biomarker for LNM. Moreover, an elevated proportion of CD38 + NK cells is associated with poor prognosis in CRC.