Serum Chemokines CCL3 and CCL7 as Complementary Diagnostic Biomarkers Across Tumor Grades in Clear Cell Renal Cell Carcinoma

TL;DR

This study shows that the chemokines CCL3 and CCL7 in blood can help detect kidney cancer and may improve early diagnosis.

Contribution

The novel finding is that CCL3 and CCL7 are oppositely regulated in kidney cancer and could serve as complementary biomarkers.

Findings

Serum CCL3 levels increase with tumor grade in clear cell renal cell carcinoma (ccRCC).

Serum CCL7 levels are significantly lower in ccRCC patients compared to healthy individuals.

CCL3 and CCL7 show complementary diagnostic performance with high sensitivity and specificity, respectively.

Abstract

The long asymptomatic period of clear cell renal cell carcinoma, which leads to delayed diagnosis and poorer prognosis, poses a global challenge. Chemokines play a pivotal role in immune regulation and tumor progression, making them promising biomarker candidates. This study aimed to evaluate the usefulness of the C-C motif chemokine ligand 3 (CCL3) and C-C motif chemokine ligand 7 (CCL7) by assessing their serum concentrations in 40 patients with stage G1 + G2 and stage G3 + G4 renal cancer, as well as in 58 healthy volunteers. Chemokine concentrations were measured using a multiplex Luminex assay and analyzed statistically, including receiver operating characteristic (ROC) analysis. Serum CCL3 concentrations were significantly elevated in ccRCC patients compared to controls and increased with tumor grade, with the highest levels observed in patients with advanced disease (G3+G4). In contrast, serum CCL7 levels were significantly lower in ccRCC patients than in healthy individuals, with no significant differences between tumor grade subgroups. ROC analysis revealed comparable diagnostic performance of CCL3 and CCL7, with CCL3 showing a slightly higher area under the curve. CCL3 showed high sensitivity, whereas CCL7 exhibited higher specificity than sensitivity, and a relatively high positive predictive value, consistent with its inverse regulation in ccRCC. These findings suggest that serum CCL3 and CCL7 are oppositely regulated in ccRCC and may serve as complementary non-invasive biomarkers for renal cancer detection.

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