Biology subjects

Kaprio, T.

Publications and source records attributed to Kaprio, T..

5 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↗

bioRxiv2025

High-resolution integrative analysis allows characterization and spatial annotation of normal and cancer-associated colon fibroblasts

Fibroblasts represent key regulators of colon homeostasis, and cancer-associated fibroblasts (CAFs) play pivotal roles in colorectal cancer (CRC). Despite their critical influence, a consensus view of adult human colon fibroblast and CRC CAF heterogeneity, spatial organization, and developmental trajectories is currently lacking. Here, we address this gap by performing a comprehensive characterization of colonic fibroblasts and CRC CAFs. Using large-scale integration of single-cell RNA-sequencing datasets from normal colon and CRC we mapped the fibroblast subpopulations. Spatial transcriptomics, immunohistochemistry, and in situ hybridization were used for validation and computational analyses to predict developmental trajectories and transcription factors underlying CAF activation. Subepithelial myofibroblasts (SEMFs), mucosa-associated fibroblasts (MAFs), and submucosa-associated fibroblasts (SAFs) were identified as the main colon fibroblast subtypes, and in mice, further divided into location-based subclusters. We also identified a novel colon fibroblast subset: muscle-embedded interstitial fibroblasts (MIFs). CRCs contained normal fibroblasts as well as four cancer-specific CAF populations: inflammatory CAFs (iCAFs), matrix CAFs (mCAFs), and two precursor CAF (preCAF) subtypes. Our data suggested that iCAFs originate from SEMFs through a preCAF1 intermediate phenotype, while mCAFs derive from SAFs/MIFs via preCAF2s. Transcription factors PRRX1, MAFB, and TWIST1 were uncovered as potential regulators of CAF identity and CTHRC1 was identified as a specific and sensitive pan-CAF marker in CRC. Our study presents a detailed framework for understanding colon fibroblast and CRC CAF heterogeneity. This work lays the groundwork for future research into the roles and potential therapeutic relevance of different CRC CAF subsets.

cancer biology↗

bioRxiv2024

HOXB6 and HOXB8 control immune-cancer cell interactions in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer lacking effective drugs and therefore new treatment targets are needed. Transcriptomic analysis comparing human embryonic and PDAC tissue identified a large overlap of expression profiles suggesting a re-initiation of developmental programs in pancreatic cancer. Specifically, we identified the transcription factors HOXB6 and HOXB8 as potential key regulators in PDAC. Loss of HOXB6 and HOXB8 in pancreatic cancer cells inhibited cell proliferation, induced apoptosis and senescence and enhanced gemcitabine sensitivity. Moreover, reduced HOXB6 and HOXB8 expression in pancreatic and lung adenocarcinoma cell lines affected transcription of immune response pathways which resulted in an increased sensitivity of cancer cells to anti-tumorigenic activities of macrophages suggesting that the HOXB6 and HOXB8 immune regulatory pattern is conserved in different cancer types. Additionally, naive M0 macrophages exposed to HOXB8 deficient PDAC cells were unable to differentiate into tumor associated macrophages, suggesting that HOXB8 promotes the transition of initial anti-tumor macrophage to a tumor-promoting macrophage phenotype in pancreatic cancer. Our findings indicate that HOXB6 and HOXB8 play important roles in regulating cell proliferation, immune response and treatment resistance to promote pancreatic cancer tumorigenesis and could be useful therapeutic targets.

cancer biology↗

bioRxiv2023

E2F transcription factors promote tumorigenicity in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with limited treatment options, illustrating an urgent need to identify new drugable targets in PDACs. Using the similarities between tumor development and normal embryonic development, which is accompanied by rapid cell expansion, we identified embryonic signalling pathways that were reinitiated during tumor formation and expansion. Here, we report that the transcription factors E2F1 and E2F8 are potential key regulators in PDAC. E2F1 and E2F8 RNA expression is mainly localized in proliferating cells in the developing pancreas and in malignant ductal cells in PDAC. Silencing of E2F1 and E2F8 in PANC-1 pancreatic tumor cells inhibited cell proliferation and impaired cell spreading and migration. Moreover, loss of E2F1 also affected cell viability and apoptosis with E2F expression in PDAC tissues correlating with expression of apoptosis and mitosis pathway genes, suggesting that E2F factors promote cell cycle regulation and tumorigenesis in PDAC cells. In conclusion, our findings show that E2F1 and E2F8 transcription factors regulate cell proliferation, survival, and migration during pancreatic carcinogenesis.

cancer biology↗