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Lung malignancies comprise lethal and aggressive tumours that remain the leading cancer-related death cause worldwide. Regarding histological classification, lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD) account for the majority of cases. Surgical resection and various combinations of chemo- and radiation therapies are the golden standards in the treatment of lung cancers, although the five-year survival rate remains very poor. Notch, Hedgehog, Wnt and Erbb signalling are evolutionarily conserved pathways regulating pivotal cellular processes such as differentiation, proliferation, and angiogenesis during embryogenesis and post-natal life. However, to date, there is no study comprehensively revealing signalling networks of these four pathways in LUSC and LUAD. Therefore, the aim of the present study was the investigation profiles of downstream target genes of pathways that differ between LUSC and LUAD biology. Our results showed a few co-expression modules, identified through weighted gene co-expression network analysis (WGCNA), which significantly differentiated downstream signaling of Notch, ErbB, Hedgehog, and Wnt in LUSC and LUAD. Among co-expressed genes essential regulators of the cell cycle, DNA damage response, apoptosis, and proliferation have been found. Most of them were upregulated in LUSC compared to LUAD. In conclusion, identified downstream networks revealed distinct biological mechanisms underlying cancer development and progression in LUSC and LUAD that may diversify the clinical outcome of the disease.

IntroductionProstate carcinoma (PRAD) is one of the most frequently diagnosed malignancies amongst men worldwide. It is well-known that androgen receptor (AR) plays a pivotal role in a vast majority of prostate tumors. However, recent evidence emerged stating that estrogen receptors (ERs) may also contribute to prostate tumor development. Moreover, progression and aggressiveness of prostate cancer may be associated with differential expression genes of epithelial-to-mesenchymal transition (EMT). Therefore we aimed to assess the significance of receptors status as well as EMT marker genes expression among PRAD patients in accordance to their age and Gleason score.Materials and methodsWe analyzed TCGA gene expression profiles of 497 prostate tumor samples according to 43 genes involved in EMT and 3 hormone receptor genes (AR, ESR1, ESR2) as well as clinical characteristic of cancer patients. Then patients were divided into four groups according to their age and 5 groups according to Gleason score. Next, we evaluated PRAD samples according to relationship between the set of variables in different combinations and compared differential expression in subsequent groups of patients. The analysis was applied using R packages: FactoMineR, gplots, RColorBrewer and NMF.ResultsMFA analysis resulted in distinct grouping of PRAD patients into four age categories according to expression level of AR, ESR1 and ESR2 with the most distinct group of age less than 50 years old. Further investigations indicated opposite expression profiles of EMT markers between different age groups as well as strong association of EMT gene expression with Gleason score. We found that depending on age of prostate cancer patients and Gleason score EMT genes with distinctly altered expression are: KRT18, KRT19, MUC1 and COL4A1, CTNNB1, SNAI2, ZEB1 and MMP3.ConclusionsOur major observation is that prostate cancer from patients under 50 years old compared to older ones has entirely different EMT gene expression profiles showing potentially more aggressive invasive phenotype, despite Gleason score classification.

IntroductionNotch signalling, an evolutionarily conserved mechanism of cellular differentiation and tissue remodelling, is frequently deregulated in several human malignancies, including renal cell carcinoma (RCC). However, the prognostic value of individual Notch pathway members in RC subtypes remains indefinable. The present study investigates whether the differential expression of Notch members has a contrary effect on disease-free survival (DFS) in clear cell renal cell carcinoma (KIRC), papillary cell renal cell carcinoma (KIRP) and chromophobe renal cell carcinoma (KICH) patients.Material and methodsThe predictive value of 19 Notch members was evaluated in KICH, KIRC and KIRP patient cohorts from The Cancer Genome Atlas (TCGA). Results in the form of Kaplan-Meier survival plots with the p-value calculated (log-rank test, p < 0.05) enabled the patients to be split into favourable/unfavourable prognosis groups regarding expression of Notch members.ResultsMore specifically, lowered expression of ADAM17 correlated with good prognosis in KICH, KIRC and KIRP (HR = 7.79, p = 0.03; HR = 3.98, p = 0.051; HR = 11.24, p < 0.001, respectively). Additionally, HES4 differentiated KICH and KIRC, as its higher expression correlated with good prognosis in KICH and favourable lowered expression in KIRC (HR = 0.11, p = 0.015; HR = 2.42, p < 0.001, respectively).ConclusionsOur analysis could be valuable for better understanding of the molecular mechanism of renal carcinoma. The expression of Notch pathway members could be a useful biomarker for predicting favourable/unfavourable prognosis in patients with RCC.

Notch signaling is an evolutionarily conserved pathway regulating normal embryonic development and homeostasis in a wide variety of tissues. It is also critically involved in carcinogenesis, as well as cancer progression. Activation of the Notch pathway members can be either oncogenic or suppressive, depending on tissue context. The present study is a comprehensive overview, extended with a bioinformatics analysis of TCGA cohorts, including breast, bladder, cervical, colon, kidney, lung, ovary, prostate and rectum carcinomas. We performed global expression profiling of the Notch pathway core components and downstream targets. For this purpose, we implemented the Uniform Manifold Approximation and Projection algorithm to reduce the dimensions. Furthermore, we determined the optimal cutpoint using Evaluate Cutpoint software to established disease-free and overall survival with respect to particular Notch members. Our results demonstrated separation between tumors and their corresponding normal tissue, as well as between tumors in general. The differentiation of the Notch pathway, at its various stages, in terms of expression and survival resulted in distinct profiles of biological processes such as proliferation, adhesion, apoptosis and epithelial to mesenchymal transition. In conclusion, whether oncogenic or suppressive, Notch signaling is proven to be associated with various types of malignancies, and thus may be of interest as a potential therapeutic target.