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. 2018 Apr 6;9(26):18548-18558.
doi: 10.18632/oncotarget.24946.

Host chemokine signature as a biomarker for the detection of pre-cancerous cervical lesions

Ramya Bhatia  1 , Kim Kavanagh  2 , June Stewart  3 , Sharon Moncur  3 , Itziar Serrano  4 , Duanduan Cong  3 , Heather A Cubie  5 , Juergen G Haas  4 , Camille Busby-Earle  6 , Alistair R W Williams  6 , Sarah E M Howie #  3 , Kate Cuschieri #  7
Affiliations

Host chemokine signature as a biomarker for the detection of pre-cancerous cervical lesions

Ramya Bhatia et al. Oncotarget. .

Abstract

Background: The ability to distinguish which hrHPV infections predispose to significant disease is ever more pressing as a result of the increasing move to hrHPV testing for primary cervical screening. A risk-stratifier or "triage" of infection should ideally be objective and suitable for automation given the scale of screening.

Results: CCL2, CCL3, CCL4, CXCL1, CXCL8 and CXCL12 emerged as the strongest, candidate biomarkers to detect underlying disease [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)]. For CIN2+, CCL2 had the highest area under the curve (AUC) of 0.722 with a specificity of 82%. A combined biomarker panel of six chemokines CCL2, CCL3, CCL4, CXCL1, CXCL8, and CXCL12 provides a sensitivity of 71% and specificity of 67%.

Conclusion: The present work demonstrates that the levels of five chemokine-proteins are indicative of underlying disease. We demonstrate technical feasibility and promising clinical performance of a chemokine-based biomarker panel, equivalent to that of other triage options. Further assessment in longitudinal series is now warranted.

Methods: A panel of 31 chemokines were investigated for expression in routinely taken archived and prospective cervical liquid based cytology (LBC) samples using Human Chemokine Proteomic Array kit. Nine chemokines were further validated using Procartaplex assay on the Luminex platform.

Keywords: HPV; biomarkers; cervical screening; chemokines; triage.

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Conflict of interest statement

CONFLICTS OF INTEREST None.

Figures

Figure 1
Figure 1
Proteomic array shows detection of chemokines in pooled aliquots from 9 samples in following categories hrHPV negative, cytological normal; hrHPV positive, CIN1; 3) hrHPV positive CIN2; and 4) hrHPV positive CIN3 (A). Relative pixel density ratio for each protein on the array was calculated using ImageJ by normalising to negative controls (NEG CONTROL) (B). Heatmap representing array results with pixel density.
Figure 2
Figure 2. Distribution of chemokine level (pg/200 ug) for ≤CIN1 versus CIN2+
Boxplots demonstrate the median, lower and upper quartile of the values, with the mean value represented as a triangle. Individual data points are shown as grey dots. Values deemed to be outliers of the distribution are shown as black dots. P values were calculated using Mann–Whitney test.
Figure 3
Figure 3. Distribution of chemokine level (pg/200 ug) for categorised disease groupings hrHPV positive ≤CIN2 versus CIN3+
Boxplots demonstrate the median, lower and upper quartile of the values, with the mean value represented as a triangle. Individual data points are shown as grey dots. Values deemed to be outliers of the distribution are shown as black dots. P values were calculated using Mann–Whitney test.
See this image and copyright information in PMC

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