Dados do Resumo

Título

Identification of potential biomarkers for differential diagnosis of lung adenocarcinoma and lung squamous cell carcinoma

Introdução

Therapeutic regimens for different histological subtypes of non-small cell lung cancer vary significantly. These personalized treatments are essential for improving efficacy and achieving satisfactory clinical outcomes in lung cancer patients. Therefore, precise diagnostic methods for the molecular and histological characterization of lung adenocarcinoma and lung squamous cell carcinoma subtypes are crucial. Studies show that keratin expression patterns are key for differentiating tumor origins.

Objetivo

In this study, we aimed to identify potential biomarkers to distinguish histological subtypes of lung adenocarcinoma and lung squamous cell carcinoma

Métodos

Seventeen samples of tumor tissue obtained from biopsies or surgical resection of lung cancer patients treated at the João de Barros Barreto University Hospital were analyzed. Total RNA was extracted using TRIzol and the Biospin Total RNA Extraction Kit II BioFlux. cDNA libraries were prepared following the Illumina Stranded Total RNA Prep, Ligation with Ribo-Zero Plus protocol, and sequenced on the Illumina Nextseq 500/550 platform. Raw data were processed using Trimmomatic, with quality reports generated by FastQC. Sequencing reads were aligned and quantified using Salmon v1.5.2 with the Genecode hg v43 version of the human genome GRCh38.p13. Differential gene expression analysis was conducted in R using the DEseq2 library. The study was approved by the Research Ethics Committee of João de Barros Barreto University Hospital under CAAE number 41667021.4.3001.0017.

Resultados

RNA-seq data analysis revealed 804 differentially expressed genes between lung adenocarcinoma and lung squamous cell carcinoma tumor samples. A total of 426 genes were up-regulated and 378 genes were down-regulated. The heatmap demonstrated differences in gene expression patterns between the histological subtypes. ROC curve analysis identified four keratin genes (KRT5, KRT6A, KRT16, KRT17) and two additional genes (SFN and TP63) as potential biomarkers for discriminating between lung adenocarcinoma and lung squamous cell carcinoma groups. Gene ontology enrichment analysis of the top 14 terms associated these genes with biological processes related to epidermis development. Upon examining normalized gene expression levels between the histological subtypes, these genes were up-regulated in lung squamous cell carcinoma and down-regulated in lung adenocarcinoma.

Conclusões

Our results suggest that differences in the expression of genes associated with epidermis development can identify specific patterns for differential diagnosis between lung adenocarcinoma and lung squamous cell carcinoma. This can guide effective treatments for non-small cell lung cancer. A precise diagnosis determining the histological and molecular characteristics of lung cancer provides valuable insights into new molecular targets in personalized medicine, enhancing therapeutic efficacy.

Financiador do resumo

FAPESPA, CCAD e CAPES

Palavras Chave

Transciptoma; RNA-seq; lung cancer