Targeted proteomic scan identifies alteration of serum proteins among workers occupationally exposed to low levels of trichloroethylene

Abstract

Occupational exposure to trichloroethylene (TCE) has been associated with alterations in B-cell activation factors and an increased risk of non-Hodgkin's lymphoma (NHL). Here, we aimed to examine the biological processes influenced by TCE exposure to understand the underlying molecular mechanisms. This cross-sectional molecular epidemiology study included data of 1317 targeted proteins in the serum from 42 TCE exposed and 34 unexposed factory workers in Guangdong, China. We used multivariable linear regressions to identify proteins associated with TCE exposure and examined their exposure-response relationship across categories of TCE exposure (unexposed, low exposed: <10 ppm, high exposed: ≥10 ppm). We further examined pathway enrichment of TCE-related proteins to understand their biological response. Occupational exposure to TCE was associated with lower levels of tumor necrosis factor receptor superfamily member 17 (TNFRSF17; β = -.08; p-value = .0003) and kynureninase (KYNU; β = -.10, p-value = .002). These proteins also showed a significant exposure-response relation across the unexposed, low exposed, and high exposed workers (all p-trends < .001, false discovery rate [FDR] < 0.20). Pathway analysis of TCE-related proteins showed significant enrichment (FDR < 0.05) for several inflammatory and immune pathways. TCE exposure was associated with TNFRSF17, a key B-cell maturation antigen that mediates B-cell survival and KYNU, an enzyme that plays a role in T-cell mediated immune response. Given that altered immunity is an established risk factor for NHL, our findings support the biological plausibility of linking TCE exposure with NHL.

Keywords: KYNU; TNFRSF17; carcinogenesis; non-Hodgkin's lymphoma; proteomics; trichloroethylene.

Fig. 1.

Box and whisker plots showing mean (95% confidence intervals) serum levels (relative fluorescence unit) of TNFRSF17 and KYNU across among 0= unexposed controls; 1= low exposed (<12ppm); and 2= high exposed (≥12 ppm) workers. Mean protein levels between TCE exposure categories were tested using linear regression models, adjusting for age, sex, smoking status and analysis batch; p-values are indicated as: *p<0.05; **p<0.01.