Comparing progression molecular mechanisms between lung adenocarcinoma and lung squamous cell carcinoma based on genetic and epigenetic networks: big data mining and genome-wide systems identification

Abstract

Non-small-cell lung cancer (NSCLC) is the predominant type of lung cancer in the world. Lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC) are subtypes of NSCLC. We usually regard them as different disease due to their unique molecular characteristics, distinct cells of origin and dissimilar clinical response. However, the differences of genetic and epigenetic progression mechanism between LADC and LSCC are complicated to analyze. Therefore, we applied systems biology approaches and big databases mining to construct genetic and epigenetic networks (GENs) with next-generation sequencing data of LADC and LSCC. In order to obtain the real GENs, system identification and system order detection are conducted on gene regulatory networks (GRNs) and protein-protein interaction networks (PPINs) for each stage of LADC and LSCC. The core GENs were extracted via principal network projection (PNP). Based on the ranking of projection values, we got the core pathways in respect of KEGG pathway. Compared with the core pathways, we found significant differences between microenvironments, dysregulations of miRNAs, epigenetic modifications on certain signaling transduction proteins and target genes in each stage of LADC and LSCC. Finally, we proposed six genetic and epigenetic multiple-molecule drugs to target essential biomarkers in each progression stage of LADC and LSCC, respectively.

Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma

“…Our results raise the possibility that SLFN12 may act in adenocarcinoma at least in part by its effects on c-myc and its downstream signals, but SLFN12 may affect a variety of transcription factors [ 11 , 12 ] and the interplay between them and their downstream effects is likely to be complex. Although adenocarcinoma of the lung and squamous cell carcinoma of the lung both derive from the same organ, their tumor biology and response to therapy are clearly different in many ways [ 46 , 47 ], and so one would not necessarily expect that the same stimulus would have the same effects in these very different tumor types.…”

Identification of candidate genes and prognostic value analysis in patients with PDL1-positive and PDL1-negative lung adenocarcinoma

“…With the development of nextgeneration sequencing technology and bioinformatics, a novel strategic solution to this problem may be identified (Morganti et al, 2019). Furthermore, previous studies have used bioinformatic analysis to explore the core genes of lung adenocarcinoma and their malignant transformation mechanisms (Yuan et al, 2017;Yeh et al, 2019). However, no research has been conducted on PDL1-positive and PDL1-negative patients.…”

Identification of Novel Cancer-Related Genes with a Prognostic Role Using Gene Expression and Protein-Protein Interaction Network Data

“…HSPA4 knockdown would be effective in therapies in cancer with head and neck squamous cell carcinoma [48]. ShanJu et al [49] constructed genetic and epigenetic networks (GENs) with LUAD and LUSC data, and identified essential biomarkers including JUN in each progression stage of LUAD and LUSC. Mutant ARAF was an oncogenic driver in LUAD and an indicator of sorafenib response [50].…”