Circulating VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ as biomarkers of cancer in cancer-associated anti-TIF1-γ antibody-positive dermatomyositis

Clin Rheumatol. 2023 Mar;42(3):817-830. doi: 10.1007/s10067-022-06425-3. Epub 2022 Nov 11.

Abstract

Objectives: The objective of the current study was to detect plasma profiles of inflammatory cytokines for determining potential biomarkers indicating cancer presence among the anti-TIF1-γ antibody-positive dermatomyositis (DM) patients.

Methods: Twenty-seven cancer-associated anti-TIF1-γ antibody-positive DM (Cancer TIF1-γ-DM) patients were compared with 20 anti-TIF1-γ antibody-positive DM patients without cancer (Non-cancer TIF1-γ-DM) and 10 healthy controls (HC). The plasma levels of 17 cytokines were determined using the Luminex 200 system. The ability of plasma VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ levels to distinguish the presence of cancer was evaluated through the area under the curve (AUC) analysis. Potential protein interactions of TIF1-γ and the five cytokines were analyzed using the STRING database.

Results: VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ plasma levels were significantly higher in the Cancer TIF1-γ-DM group, especially those without any anticancer treatment, than those in the non-cancer TIF1-γ-DM and HC groups. Meanwhile, anti-TIF1-γ antibody and the five cytokines could distinguish cancer presence in anti-TIF1-γ antibody-positive DM patients. The STRING network indicated that TIF1-γ potentially interacted with the cytokines. Positive correlations of VEGF-A among CCL2, IL-6, and IFN-γ and between IFN-γ and IL-6 were observed in Cancer TIF1-γ-DM patients. VEGF-A, TNF-α, CCL2, and IL-6 were positively associated with muscle-associated enzymes among the Cancer TIF1-γ-DM patients.

Conclusion: The present study identified VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ as significant potential biomarkers indicating the presence of cancer and demonstrated a more detailed cytokine profile during diagnosis. These biomarkers could provide better screening strategies and insight into the Cancer TIF1-γ-DM pathogenesis. Key Points • VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ are potential biomarkers of cancer in cancer-associated anti-TIF1-γ antibody-positive dermatomyositis. Potential pathogenic molecular mechanism of the cancer-associated anti-TIF1-γ antibody-positive dermatomyositis.

Keywords: Anti-TIF1-γ antibody; Biomarker; Cancer; Cytokine; Dermatomyositis.

MeSH terms

  • Autoantibodies
  • Biomarkers
  • Chemokine CCL2
  • Cytokines
  • Dermatomyositis* / complications
  • Dermatomyositis* / diagnosis
  • Humans
  • Interferon-gamma
  • Interleukin-6
  • Neoplasms* / complications
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Vascular Endothelial Growth Factor A
  • Autoantibodies
  • Cytokines
  • Biomarkers
  • Interferon-gamma
  • CCL2 protein, human
  • Chemokine CCL2