Personalized and Precision Medicine Journal

Abstract KRAS-driven lung adenocarcinoma is molecularly heterogeneous; however, evaluation of mutation-associated programs requires matched mutation and clinical metadata. Here, three GDC STAR-count RNA-sequencing files annotated with GENCODE v36 were analyzed to determine which transcriptomic conclusions could be supported from the available data alone. Protein-coding TPM values were used for library-level quality assessment, transcriptome-wide correlation, principal component analysis, sample-specific expression contrasts, and exploratory scoring of curated KRAS/MAPK, PI3K–AKT–mTOR, cell-cycle, epithelial-lineage, epithelial–mesenchymal transition, hypoxia, inflammatory, interferon, apoptosis, and NRF2-related gene sets. The samples contained 24.3–49.5 million assigned reads and 12,808–14,574 protein-coding genes with TPM ≥1. Pairwise transcriptome correlations ranged from r=0.745 to 0.825. Marked biological heterogeneity was observed. Sample 1 showed a secretory epithelial profile characterized by PAEP, CEACAM5, CEACAM6, BPIFA1, and EPCAM. Sample 2 displayed a keratinizing/squamous-like program dominated by KRT5, KRT6A, KRT14, KRT17, SPRR family genes, and elevated NRF2-associated and glycolytic scores. Sample 3 exhibited a strong alveolar-lineage and immune-associated profile, with high SFTPA1, SFTPA2, SFTPB, SFTPC, HLA-DRA, CD74, and inflammatory pathway scores. KRAS expression was detectable in all samples (16.33–30.09 TPM), but RNA expression alone could not establish KRAS mutation status. These findings demonstrate substantial lineage and pathway heterogeneity among the three transcriptomes and provide a hypothesis-generating framework for subsequent mutation-informed analysis. Mutation-stratified differential expression, prognostic modeling, and survival analysis were not performed because mutation and clinical outcome data were unavailable.

Abstract Background: Leishmania Species produced diseases include clinical problems from cutaneous self-limiting to severe non-healing forms such as visceral leishmaniasis (VL). As an obligatory intracellular parasite these pathogens proliferate and survive inside macrophages in animals and human; while these cells as a major host immune cell destroy majority of disease producing agents. Because macrophages act as first line of innate immunity, produce several molecules when activated. Proinflammatory and inflammatory cytokines are produced by these cells through their activation, act as main coordinators of the immune system against pathogens and other harmful disease producing factors against the body. Through such a mechanism the immune response resolves the problem.  To play such a critical role many cells as monocytes, macrophages, DCs and others involved in T cell regulation to establish proper innate and adaptive immunity responses. Proinflammatory and inflammatory cytokines are produced in a network acting through many signal pathways.
Methods: In this descriptive designed study, quality-controlled cDNA samples sequenced (RNA-seq) and mapped against a standard human genome version. Results: Based on the results of this study, proinflammatory and inflammatory gene expressions were significantly upregulated.
Conclusion: Upregulations of proinflammatory and inflammatory gene expressions early infection time might be indication for an early  innate immunity response.