CD4 levels and NSCLC metastasis: the benefits of maintaining moderate levels

Abstract

Objectives: Prior researches indicate that peripheral blood CD4 levels have an inverse correlation with distant tumor metastasis in non-small cell lung cancer (NSCLC). However, the linear relationship between CD4 and distant metastasis lacks clarity. Hence, the objective of this study was to ascertain the linear relationship between CD4 and distant metastasis in NSCLC patients.

Methods: This retrospective study analyzed clinical and laboratory data of NSCLC patients between March 2016 and July 2022 at the Cancer Hospital of Anhui University of Technology. The study first applied a generalized summation model and smoothing curve fitting to determine if there was a linear relationship between CD4 and NSCLC metastasis. Secondarily, univariate logistic analysis and multiple linear regression were used to analyze the odds ratio (OR) of CD4 as a continuous variable, dichotomous variable, and trichotomous variable when predicting NSCLC metastasis. In addition, stratified and subgroup analyses were conducted to assess the reliability of CD4 in different NSCLC patient populations.

Results: The study included a total of 213 NSCLC patients, among which 122 had distant metastasis and 91 had no metastasis. The smoothing curve fitting analysis revealed a U-shaped relationship between CD4 and NSCLC metastasis with a threshold effect. The univariate logistic analysis indicated that continuous CD4 expression was not significantly associated with NSCLC metastasis (P = 0.051); however, high levels of CD4 expression (≥ 35.06%) were found to be a protective factor against NSCLC metastasis when CD4+ T was a dichotomous variable (OR = 0.49, P = 0.010). Furthermore, multivariate linear regression models showed that low (< 32%) or high levels (> 44%) of CD4 significantly increased the risk of NSCLC metastasis compared to medium levels (32-44%) when CD4+ T was trichotomized. The significance was maintained in stratified analysis in relation to age, sex, type of pathology, smoke, PS, and T stage. CD4 levels were U-shaped in relation to different sites of distant metastases (bone, brain, liver), but not with lung metastases.

Conclusions: A threshold effect is shown to exist between the peripheral blood CD4 and distant metastasis in NSCLC patients. It was revealed that the risk of distant metastasis is lower when CD4 is maintained between 32 and 44%, whereas low (< 32%) or high (> 44) levels of CD4 are associated with an increased risk of distant metastasis in NSCLC patients.

Keywords: CD4+ T cell; Lymphocyte; Metastasis; Non-small cell lung cancer.