Racial Differences in Chemokine Expression May Contribute to Prostate Cancer Disparities

Biological factors, such as certain chemokine levels, could help explain higher prostate cancer (PCa) incidence and mortality rates in African American (AA) patients, according to a recent study published in Cancer.

Despite recent advancements and progress, an “overwhelming majority” of patients with PCa still relapse. Data continually show that AA patients are a disproportionately affected demographic, experiencing twice the burden of mortality compared with Caucasian (CA) patients.

The underlying mechanisms in this disparity are not fully understood. Research points to age, genetics, lifestyle, diet, access to health care, and more as risk factors influencing these effects; however, when past studies adjusted for non-biological factors, mortality rates were still significantly higher in AA patients.

Prostate Cancer | Dr_microbe - stock.adobe.co

Systemic inflammation and immune responses have emerged as potential influences in PCa aggression. The researchers point to the various inflammatory factors present in the prostate tumors of AA patients, such as higher levels of IFN-g-related genetic signatures, proinflammatory cytokines, and macrophage inhibitory cytokines (MIC-1), among others. However, the concentrations of these inflammatory markers can differ between AA and CA patients.

To better explore this disparity and understand the role of systemic inflammation in AA patients with PCa, the serum levels of various chemokines and cytokines were profiled from preoperative PCa patients.

All cases of PCa (N = 171) were age-matched with healthy controls (N = 40). A 40-plex human chemokine assay was used to widely assess 40 chemokine/cytokines in addition to an enzyme-linked immunosorbent assay that focused on measuring chemokines CXCL2, CXCL5, and CCL23. Tissue microarray (TMA) was also conducted to evaluate how certain chemokines were expressed in different prostate tumors.

In the 40-plex human chemokine assay, serum levels were measured from 11 healthy controls and 28 patients with PCa (14 AA patients and 14 CA). Independent of racial composition, results showed significantly lower serum levels in PCa patients in the chemokines CCL1 (P = .006), CCL7 (P = .015), CCL8 (P = .001), CCL11 (P = .008), CCL13 (P < .0001), CXCL9 (P = .014), CXCL10 (P = .043); and the cytokine IL‐2 (P = .047) and TNF‐α (P = .005).

In contrast, differences specific to race were observed in significantly elevated levels of CXCL2 (P < .0001), CXCL5 (P = .016), and IL‐6 (P = .004); and lower levels of CCL23 (P < .0001) and CCL27 (P = .016) in AA PCa patients compared to CA patients.

The chemokines CXCL2, CXCL5, and CCL23 showed significantly different expressions in AA patients compared with CA. For CXCL5, AA men registered values that were 1.52 points higher than CA men (P < .001). CXCL2 outcomes were similar, with AA men registering higher serum levels. In CCL23, however, AA men had significantly lower levels than their CA counterparts. Among AA men, CCL23 levels were also significantly lower in PCa cases compared to healthy AA controls. CA patients with PCa had slightly lower levels than CA controls as well, but this was not noted as significant.

TMA results to examine prostate tumors revealed that CXCL5 expression was significantly higher in malignant tissue compared to adjacent benign tissue (P < .001). There were not any significant race-specific differences (P = .62), however, and the same was true for CCL23 expression.

The researchers’ findings suggest that elevated serum levels of CXCL2 and CXCL5 chemokines—in addition to lower CCL23 levels—play a role in immunity responses to lethal forms of PCa in AA men. They claim that their “observations pose the question of whether the increased level of serum CXCL2 and CXCL5 in AA subjects (healthy controls and prostate cancer cases) is a consequence of genetic differences or results from environmental factors, including diet and lifestyle contribute to racial disparity in prostate cancer outcomes.”

Nevertheless, highlighting the importance of disproportionate serum chemokine levels can be a useful guide for managing the care of AA patients with aggressive forms of PCa. With these uncertainties still looming in research, further studies are necessary to explore these associations.

Reference

Karan D, Wick J, Dubey S, et al. Racial differences in serum chemokines in prostate cancer patients. Cancer. Published online September 12, 2023. doi: 10.1002/cncr.35012