Iga Kołodziejczak-Guglas

Cancer progression and therapeutic resistance are closely linked to a stemness phenotype. Here, we introduce a protein-expression-based stemness index (PROTsi) to evaluate oncogenic dedifferentiation in relation to histopathology, molecular features, and clinical outcomes. Utilizing datasets from the Clinical Proteomic Tumor Analysis Consortium across 11 tumor types, we validate PROTsi's effectiveness in accurately quantifying stem-like features. Through integration of PROTsi with multi-omics, including protein post-translational modifications, we identify molecular features associated with stemness and proteins that act as active nodes within transcriptional networks, driving tumor aggressiveness. Proteins highly correlated with stemness were identified as potential drug targets, both shared and tumor specific. These stemness-associated proteins demonstrate predictive value for clinical outcomes, as confirmed by immunohistochemistry in multiple samples. The findings emphasize PROTsi's efficacy as a valuable tool for selecting predictive protein targets, a crucial step in customizing anti-cancer therapy and advancing the clinical development of cures for cancer patients.

Recent advancements in proteomics have enhanced our understanding of clear cell renal cell carcinoma (CCRCC). Utilizing a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by immunohistochemical validation, we investigated the expression levels of UCHL1, PAK4, and SNRNP200 in high-grade CCRCC samples. Our analysis also integrated Reactome pathway enrichment to elucidate the roles of these proteins in cancer-related pathways. Our results revealed significant upregulation of UCHL1 and SNRNP200 and downregulation of PAK4 in high-grade CCRCC tissues compared to non-cancerous tissues. UCHL1, a member of the ubiquitin carboxy-terminal hydrolase family, showed variable expression across different tissues and was notably involved in the Akt signaling pathway, which plays a critical role in cellular survival in various cancers. SNRNP200, a key component of the RNA splicing machinery, was found to be essential for proper cell cycle progression and possibly linked to autosomal dominant retinitis pigmentosa. PAK4's role was noted as critical in RCC cell proliferation and invasion and its expression correlated significantly with poor progression-free survival in CCRCC. Additionally, the expression patterns of these proteins suggested potential as prognostic markers for aggressive disease phenotypes. This study confirms the upregulation of UCHL1, SNRNP200, and PAK4 as significant factors in the progression of high-grade CCRCC, linking their enhanced expression to poor clinical outcomes. These findings propose these proteins as potential prognostic markers and therapeutic targets in CCRCC, offering novel insights into the molecular landscape of this malignancy and highlighting the importance of targeted therapeutic interventions.

Clear-cell renal cell carcinoma (ccRCC) is a kidney cancer associated with poor prognosis and limited treatment options. Identifying new prognostic markers is crucial. This study investigates the potential of BCL9 and TPX2, two proteins involved in cancer progression, to predict patient outcomes This study analyzed protein abundance data from the CPTAC cohort (110 ccRCC and 84 NAT samples) using LC-MS/MS. BCL9 and TPX2 were validated via immunohistochemistry (IHC) in an independent cohort (52 ccRCC samples). Patients were stratified into high- and low-expression groups based on IHC scores. Survival analyses were conducted, and Reactome pathway enrichment analysis was performed. BCL9 and TPX2 were significantly upregulated in ccRCC compared to NAT. In the validation cohort, high BCL9 levels were associated with shorter progression-free survival (PFS) but not OS, while high TPX2 levels correlated with shorter overall survival (OS) but not PFS. Pathway analysis linked BCL9 to Wnt signaling and TPX2 to cell cycle regulation. Elevated BCL9 and TPX2 are associated with poor prognosis in ccRCC. These proteins are potential prognostic markers and therapeutic targets.

Clear cell renal cell carcinoma (ccRCC) is a significant global cancer, particularly impacting individuals in Western countries. Despite that, the molecular mechanisms driving renal cell carcinoma progression remain poorly understood, highlighting the need to investigate these mechanisms and identify novel therapeutic targets. Literature evidence suggests that elongation factor Tu GTP binding domain containing 2 (EFTUD2) and prominin (PROM1) gene expression have significant diagnostic potential in early tumor detection, potentially reflecting the trends in progression, and may become a novel therapeutic target. Therefore, this study aimed to evaluate EFTUD2 and PROM1 protein expression on clinical characteristics of ccRCC patients, especially overall and progression-free survival. To achieve that goal, we have combined publicly available liquid chromatography-mass spectrometry (LC-MS/MS) protein expression data with a comprehensive literature review to identify key protein markers for further study and immunohistochemical (IHC) analysis. Our findings highlight the importance of considering protein expression heterogeneity within tumors. The significant variation in EFTUD2 expression, its association with PFS, and its intricate connections with the mRNA splicing machinery underscore the need for a more nuanced understanding of its role in ccRCC. Similarly, the downregulation of PROM1 and its potential effects on cell surface interactions warrant further exploration. Future studies should focus on elucidating the mechanisms underlying these observations, exploring their potential as therapeutic targets, and investigating the specific pathways affected by their dysregulation.

Gastric cancer is marked by profound molecular and microenvironmental heterogeneity that limits therapeutic progress. Here, we present a 15-layer multi-omics atlas that integrates genomics, epigenomics, transcriptomics, proteomics, multiple post-translational modifications (PTMs), protein-protein interactions, metabolomics, and microbiome profiles from 159 primary gastric adenocarcinomas and 30 matched normal adjacent tissues. Using cell-state deconvolution, we define tumor ecotypes that refine genomic and histological subtypes by capturing distinct tumor microenvironment architectures linked to clinical outcomes and potential associations with immunotherapy response. Multi-omics integration prioritizes genomic and epigenomic aberrations and their associated vulnerabilities; defines ecotype-specific transcriptional programs, signaling pathways, PTMs, protein interaction networks, and metabolic regulation; and identifies microbiome features linked to ecotypes and resistance pathways. We further prioritize ecotype-, genomic subtype-, and cell type-specific targetable proteins using proteomic and PTM analyses within a tumor microenvironment context. This comprehensive atlas provides a systems-level blueprint for decoding gastric cancer heterogeneity and advancing precision oncology.