Blood protein CXCL2 shows strong accuracy detecting endometrial cancer before surgery

Three proteins circulating in the blood — p21-activated kinase 1 (PAK1), the transcription factor Snail, and the chemokine CXCL2 — have been tested as preoperative markers for endometrial cancer in a prospective, single-center case-control study published in BMC Women’s Health. The central result concerns CXCL2: serum concentrations of this chemokine were markedly lower in women with endometrial cancer than in women undergoing surgery for benign gynecologic disease, and this single measurement discriminated between the two groups with an area under the receiver operating characteristic curve (AUC) of 0.923 (95% CI 0.877–0.970), corresponding to a sensitivity of 86.4% and a specificity of 94.3%.

Those checks supported the main finding. In the age- and BMI-matched subgroup, CXCL2 discrimination was even stronger, with an AUC of 0.958 (95% CI 0.906–1.000), and among postmenopausal women the AUC was 0.926 (95% CI 0.878–0.974). The chemokine also added information beyond basic clinical variables: adding CXCL2 to age and BMI raised the AUC from 0.841 (95% CI 0.781–0.900) to 0.953 (95% CI 0.920–0.985), a difference that was statistically significant by DeLong testing (p < .001).

The other two proteins behaved differently. PAK1 and Snail did not differ between cancer cases and benign controls in univariate comparisons, but both contributed independently in a multivariable logistic regression model that also retained CXCL2, BMI, and menopausal status; that combined model reached a pseudo R² of 0.66. This pattern suggests that while PAK1 and Snail are not useful as stand-alone screening tests, they may carry complementary information when considered alongside other clinical and molecular variables.

Within the cancer group itself, serum PAK1 was higher in FIGO stage II-III disease than in stage I (p = .011). In contrast, none of the three markers varied significantly by tumor grade, meaning they did not distinguish well-differentiated from poorly differentiated tumors in this cohort.

The biological rationale for testing these particular molecules comes from two pathways implicated in endometrial carcinogenesis. CXCL2 is a chemokine, and chemokine signaling is implicated in endometrial carcinogenesis. The authors note that the value of such circulating mediators as preoperative, blood-based markers had remained poorly defined prior to this work.

However, the authors are explicit about the limits of the evidence. They describe the findings as exploratory and hypothesis-generating, noting that they will need confirmation in an independent cohort and testing against molecular subtype classification and survival data. The case-control design, in which women with cancer were compared with women operated on for benign disease, establishes diagnostic discrimination in a controlled setting but does not by itself establish performance as a screening test in the general population. The single-center design and the demographic adjustments required between groups further underline the preliminary nature of the results.

With those caveats in place, the study delivers a concrete, quantified signal: a chemokine measured in a preoperative blood sample, lower rather than higher in cancer, that separates endometrial cancer from benign gynecologic disease with high reported accuracy and holds up across matched, postmenopausal, and covariate-adjusted analyses. If independent cohorts reproduce the CXCL2 result and clarify what PAK1 and Snail add in multivariable models, these circulating EMT and chemokine markers could become candidates for incorporation into preoperative risk assessment for endometrial cancer.

Subject of Research: Preoperative serum PAK1, Snail, and CXCL2 as diagnostic and stage-associated markers in endometrial cancer

Article Title: Preoperative serum PAK1, snail, and CXCL2 in endometrial cancer: diagnostic discrimination and association with tumor stage in a prospective case-control study

Article References: Atalmış, H. A., Tuna, G., Şahin, G., & Yıldız, A. (2026). Preoperative serum PAK1, snail, and CXCL2 in endometrial cancer: diagnostic discrimination and association with tumor stage in a prospective case-control study. BMC Women's Health. https://doi.org/10.1186/s12905-026-05030-9

Image Credits: AI Generated

DOI: 10.1186/s12905-026-05030-9

Keywords: endometrial cancer, CXCL2, PAK1, Snail, biomarkers, ELISA, case-control study, ROC analysis, epithelial-mesenchymal transition, tumor stage, BMC Women's Health, diagnostic markers