Biology subjects

Bockelman, C.

Publications and source records attributed to Bockelman, C..

3 recordsLinked to original sources

bioRxiv2025

CXCL12, SCF, and eotaxin are prognostic serum biomarkers in gastric cancer

Gastric cancer is the fifth most common cancer worldwide and the fifth leading cause of cancer-related death. Its poor prognosis is primarily due to a late diagnosis and a lack of effective treatments for advanced disease. We aimed to identify new prognostic serum biomarkers to aid clinical decision-making. Our patient cohort consisted of 240 individuals who underwent surgery for histologically verified gastric adenocarcinoma in the Department of Surgery, Helsinki University Hospital, between 2000 and 2009. To determine serum protein concentrations of cytokines and growth factors, we utilized Bio-Rads premixed Bio-Plex Pro Human Cytokine 27-plex and 21-plex assay kits. Among the 48 biomarkers analyzed, three emerged as statistically significant prognostic markers for disease-specific survival using the Cox proportional hazards univariate analysis: C-X-C motif chemokine ligand 12 (CXCL12) (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.23-0.63, p<0.001), stem cell factor (HR 0.38, 95%CI 0.19-0.77, p=0.007), and eotaxin (HR 0.57, 95%CI 0.37-0.89, p=0.013). Multivariate survival analysis revealed that, among the 48 biomarkers analyzed, CXCL12 and eotaxin served as independent prognostic markers among gastric cancer patients. The prognostic effect of inflammatory serum biomarkers in gastric cancer could provide new insights into the immunological microenvironment of disease.

pathology↗

bioRxiv2025

CCL5, CLEC11A, IL-7, IL-8, and IL-13: Diagnostic serum biomarkers of gastric cancer identified in a 48-multiplex panel

BackgroundGastric cancer is the fifth most common cancer worldwide and the fifth leading cause of cancer-related death. Its poor prognosis is primarily due to a late diagnosis and a lack of effective treatments for advanced disease. MethodsWe examined a patient cohort comprising 239 individuals who underwent surgery for histologically verified gastric adenocarcinoma in the Department of Surgery at Helsinki University Hospital between 2000 and 2009, comparing them to 48 healthy controls. We measured the serum protein concentrations for 48 different cytokines and growth factors using two of Bio-Rads premixed Bio-Plex Pro Human Cytokine 27-plex and 21-plex assay kits. ResultsFive serum biomarkers were identified as indicative of gastric cancer. Cancer patients had higher serum levels of CLEC11A [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.08- 1.26, p = 0.004], IL-7 (OR 2.73, 95% CI 1.48-5.04, p = 0.014), IL-8 (OR 6.30, 95% CI 2.23-20.0, p = 0.017), and IL-13 (OR 2.67, 95% CI 1.33-5.37, p = 0.041). The CCL5 levels were lower in cancer patients compared with controls (OR 0.30, 95% CI 0.14-0.60, p = 0.014). ConclusionsIn a large cohort of 239 patients, we identified five biomarkers for which serum levels associated with gastric cancer: CCL5, CLEC11A, IL-7, IL-8, and IL-13. High serum levels of CLEC11A have not previously been associated with gastric cancer. Our results provide new support to further explore the effect of these inflammatory molecules and the role they play in gastric cancer. This may help identify novel noninvasive diagnostic methods as well as potential new druggable targets.

pathology↗

bioRxiv2021

Ovarian cancers with low CIP2A tumor expression constitute an APR-246 sensitive disease subtype

Identification of ovarian cancer (OvCa) patient subpopulations with increased sensitivity to targeted therapies could offer significant clinical benefit. We report that 22% of the high grade OvCa tumors at diagnosis express CIP2A oncoprotein at low levels. CIP2Alow OvCa tumors have significantly lower likelihood of disease relapse after standard chemotherapy, but yet a portion of relapsed tumors retain their CIP2Alow phenotype. We further discover that reactive oxygen species (ROS) inducing compound APR-246 (PRIMA-1Met/Eprenetapopt), currently in clinical development, preferentially kill CIP2Alow OvCa cells across multiple chemotherapy resistant cell lines. Consistent with CIP2Alow OvCa subtype in humans, CIP2A is dispensable for development of MISIIR-TAg-driven mouse OvCa tumors. Nevertheless, CIP2A deficient OvCa tumor cells from MISIIR-TAg mice displayed APR-246 hypersensitivity both in vitro and in vivo. Mechanistically, the lack of CIP2A expression hypersensitizes the OvCa cells to APR-246 by inhibition of NF-kB activity. Accordingly, combination of APR-246 and Nf-kB inhibitor compounds strongly synergized in killing of CIP2A positive OvCa cells. Collectively, we discover low CIP2A expression as a vulnerability for APR-246 in OvCa. The results warrant consideration of clinical testing of APR-246 for CIP2Alow OvCa tumor subtype patients, and reveal CIP2A as a candidate APR-246 combination therapy target.

cancer biology↗