Cancer cells utilise several mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm, and epigenetic regulation by microRNAs (miRNAs). Because it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced, and the cancer cells may have acquired drug resistance. This review summarises the main mechanisms involved in cisplatin resistance and interactions between cisplatin-resistant cancer cells and the tumour microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin-resistant non-small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly dysregulated TP53, MDM2, and CDKN1A genes as they encode the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

The aim of the study was a search for diagnostic and/or prognostic biomarkers in patients with non-small cell lung cancer (NSCLC) patients, based on circulating microRNAs (miRs: miR-23a, miR-361, miR-1228 and miR-let7i) in extracellular vesicles (EVs). Serum EVs were isolated from NSCLC patients (n = 31) and control subjects (n = 21). RNA was isolated from EVs and reverse transcription reaction was performed. Relative levels of miR-23a, miR-361, miR-1228 and miR-let7i were assessed in real-time qPCR using TaqMan probes. Analysis was based on the 2-ΔΔCT method. Statistically significant lower levels of miR-23a and miR-let7i were observed among NSCLC patients vs. control group: miR-23a, 0.054 vs. 0.107; miR-let7i, 0.193 vs. 0.369 (p = 0.003, p = 0.005, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential of each individual serum EV-derived miRNA with an area under the curve AUC = 0.744 for miR-23a (p = 0.0003), 0.733 for miR-let7i (p = 0.0007). The decreased level of miR-23a in patients correlated with metastasis to lymph nodes and with AJCC tumor staging system. The results demonstrate that miR-23a and miR-let7i may prove clinically useful as significant, non-invasive markers in NSCLC diagnosis. Additionally, changing profile level of miR-23a that correlates with cancer development may be considered as an NSCLC progression marker.

One of the main treatment modalities for non-small-cell lung cancer (NSCLC) is cisplatin-based chemotherapy. However, the acquisition of cisplatin resistance remains a major problem. Existing chemotherapy regimens are often ineffective against cancer cells expressing aldehyde dehydrogenase (ALDH). As such, there is an urgent need for therapies targeting ALDH-positive cancer cells. The present study compares the anticancer properties of 36 structurally diverse isothiocyanates (ITCs) against NSCLC cells with the ALDH inhibitor disulfiram (DSF). Their potential affinity to ALDH isoforms and ABC proteins was assessed using AutoDockTools, allowing for selection of three compounds presenting the strongest affinity to all tested proteins. The selected ITCs had no impact on NSCLC cell viability (at tested concentrations), but significantly decreased the cisplatin tolerance of cisplatin-resistant variant of A549 (A549CisR) and advanced (stage 4) NSCLC cell line H1581. Furthermore, long-term supplementation with ITC 1-(isothiocyanatomethyl)-4-phenylbenzene reverses the EMT phenotype and migratory potential of A549CisR to the level presented by parental A549 cells, increasing E-Cadherin expression, followed by decreased expression of ABCC1 and ALDH3A1. Our data indicates that the ALDH inhibitors DSF and ITCs are potential adjuvants of cisplatin chemotherapy.

Application of the FOLFOX scheme to colorectal cancer (CRC) patients often results in the development of chemo-resistance, leading to therapy failure. This study aimed to develop a functional and easy-to-use algorithm to predict patients’ response to FOLFOX treatment. Transcriptomic data of CRC patient’s samples treated with FOLFOX were downloaded from the Gene Expression Omnibus database (GSE83129, GSE28702, GSE69657, GSE19860 and GSE41568). Comparing the expression of top up- and downregulated genes in FOLFOX responder and non-responder patients’ groups, we selected 30 potential markers that were used to create a step-by-step eliminative procedure based on modified radial data visualization, which depicts the interplay between the expression level of chosen attributes (genes) to locate data points in low-dimensional space. Our analysis proved that FOLFOX-resistant CRC samples are predominantly characterized by upregulated expression levels of TMEM182 and MCM9 and downregulated LRRFIP1. Additionally, the procedure developed based on expression levels of TMEM182, MCM9, LRRFIP1, LAMP1, FAM161A, KLHL36, ETV5, RNF168, SRSF11, NCKAP5, CRTAP, VAMP2, ZBTB49 and RIMBP2 proved to be capable in predicting FOLFOX therapy response. In conclusion, our approach can give a unique insight into clinical decision-making regarding therapy scheme administration, potentially increasing patients’ survival and, consequently, medical futility due to incorrect therapy application.

Osteoarthritis (OA) is the most common degenerative joint disease, leading to severe pain and functional disability for nearly 530 million people worldwide. OA is characterized by progressive loss of cartilage and synovial hyperplasia from the articulating surfaces of any diarthrodial joints, however, the majority of cases account for the hip and knee. Currently, regenerative therapy based on stem cells has emerged as one of the most promising and rapidly evolving strategies in OA. Although progression and potential regeneration can be monitored by magnetic resonance imaging (MRI), we lack proper molecular markers of joint regeneration for diagnostic and in vitro studies. Gene expression profiles of articular cartilage (chondrocytes) and synovium from OA-affected patients’ were downloaded from The Gene Expression Omnibus database (GSE179716, GSE206848, GSE239343, GSE48556) and analyzed using various bioinformatic tools and platforms: GEO2R, FunRich, C-Big, The Human Protein Atlas, STRING, Orange data mining, Jasp, Gene Ontology and Reactome. OA-affected synovium and chondrocytes present differences between aurora B and A signaling. However, major biological pathways are similarly enriched with SRI, SMC2, PSIP1, TLE4, and MSX1 genes identified as prominent molecular biomarkers of OA progression and mesenchymal stem cell-based OA regeneration. Additionally, in peripheral blood mononuclear cells (PBMCs) from OA patients PSIP1 and TLE4 present (respectively) down and up-regulated mRNA levels. mRNA expression levels of chosen genes can indicate OA progression mainly in the in vitro studies, whereas the mRNA level ratio of PSIP1:TLE4 from PBMCs derived from OA patients can help monitor OA progression in clinical practice.

Lung cancer is one of the most diagnosed types of cancer, accounting for nearly two million deaths worldwide each year. 1 Its complex etiopathology involves a mix of genetic predispositions and env...