Marker For Lung Squamous Cell Carcinoma Research Articles

Regulator of nonsense transcripts 3B is a prognostic biomarker and associated with immune cell infiltration in lung squamous cell and hepatocellular carcinoma

PurposeThe characteristic of RENT3B in cancer remains ambiguous. We aimed to study the relationship between RENT3B and immune infiltration in liver hepatocellular carcinoma (LIHC) and lung squamous cell carcinoma (LUSC).Patients and methodsWe investigated the expression levels of RENT3B using ONCOMINE and TIMER databases, and assessed the interrelationship between RENT3B expression and survival using PrognoScan, GEPIA, and Kaplan–Meier plotter. Additionally, we examined the association between RENT3B and immune cells in the tumor microenvironment (TME), as well as markers of immune cells, using TIMER. Subsequently, we performed prognostic analysis based on the expression level of RENT3B within specific immune cell subgroups. Furthermore, we evaluated the promoter methylation profile of RENT3B between tumor and normal tissues in LIHC and LUSC using the DNMIVD database.ResultsRENT3B exhibited increased levels in both in LIHC and LUSC. High RENT3B expression was associated with unfavorable prognosis in LIHC, whereas it indicated a beneficial prognosis in LUSC. In LIHC, the expression of RENT3B positively correlated with immune infiltration levels of B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells. However, in LUSC, the expression of RENT3B showed a negative correlation with immune infiltration levels of B cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells. RENT3B exhibited positive correlations with 42 immune markers in LIHC, while it displayed negative associations with 10 immune markers in LUSC. Despite variations in immune cell enrichment and reduction subgroups, high RENT3B expression consistently indicated poor prognosis in LIHC, whereas it remained favorable in LUSC. Additionally, there were no significant differences observed in RENT3B promoter methylation between tumor and normal tissues in both LIHC and LUSC.ConclusionRENT3B can affect the overall tumor prognosis and is associated with immune infiltration, especially in LIHC and LUSC. Consequently, RENT3B can become a prognostic biomarker for LIHC and LUSC.

Predicting the Lung Squamous Cell Carcinoma Diagnosis and Prognosis Markers by Unique DNA Methylation and Gene Expression Profiles.

The early diagnosis of lung squamous cell carcinoma (LUSC) is difficult, causing an unsatisfactory prognosis. Therefore, the 5-year survival rate of LUSC is poor. This study aimed at screening the potential diagnostic and prognostic markers for LUSC. The data of LUSC gene expression profiles and DNA methylation were obtained from The Cancer Genome Atlas (TCGA) database; the differentially expressed genes (DEGs) and the differentially methylated genes (DMGs) were screened out by an independent t-test and Benjamini/Hochberg methods. Further, the classifiers of the gene expression and DNA methylation markers in LUSC were constructed. After that, diagnostic and prognostic markers in LUSC were analyzed by the protein-protein interaction (PPI) network. The DEGs and the DMGs from TCGA database of LUSC were screened out. After strict filtration, we identified three potential DMGs (POU domain, class 4, transcription factor 2 [POU4F2], EN1, single-minded homolog 1 [SIM1]) for early diagnosis and seven potential DEGs (G-protein coupled receptor 78 [GPR78], PCDHA5, myosin binding protein H [MYBPH], RTL3, KIAA0408, HSD3B2, PCDHA12) for prognosis of LUSC. The tumor-normal tissue classification model and prognosis model were validated in two independent datasets. In addition, the PPI network was constructed, including three DMGs and the five DEGs (GPR78, MYBPH, KIAA0408, HSD3B2, PCDHA12) of the seven DEGs. The potential DMGs (POU4F2, EN1, SIM1) and DEGs (GPR78, MYBPH, KIAA0408, HSD3B2, PCDHA12) for the diagnosis and prognosis of LUSC identified in this article are expected to be further applied in clinical practice of the treatment of LUSC.

Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma

Traditionally, non-small cell lung cancer is treated as a single disease entity in terms of systemic therapy. Emerging evidence suggests the major subtypes--adenocarcinoma (AC) and squamous cell carcinoma (SqCC)--respond differently to therapy. Identification of the molecular differences between these tumor types will have a significant impact in designing novel therapies that can improve the treatment outcome. We used an integrative genomics approach, combing high-resolution comparative genomic hybridization and gene expression microarray profiles, to compare AC and SqCC tumors in order to uncover alterations at the DNA level, with corresponding gene transcription changes, which are selected for during development of lung cancer subtypes. Through the analysis of multiple independent cohorts of clinical tumor samples (>330), normal lung tissues and bronchial epithelial cells obtained by bronchial brushing in smokers without lung cancer, we identified the overexpression of BRF2, a gene on Chromosome 8p12, which is specific for development of SqCC of lung. Genetic activation of BRF2, which encodes a RNA polymerase III (Pol III) transcription initiation factor, was found to be associated with increased expression of small nuclear RNAs (snRNAs) that are involved in processes essential for cell growth, such as RNA splicing. Ectopic expression of BRF2 in human bronchial epithelial cells induced a transformed phenotype and demonstrates downstream oncogenic effects, whereas RNA interference (RNAi)-mediated knockdown suppressed growth and colony formation of SqCC cells overexpressing BRF2, but not AC cells. Frequent activation of BRF2 in >35% preinvasive bronchial carcinoma in situ, as well as in dysplastic lesions, provides evidence that BRF2 expression is an early event in cancer development of this cell lineage. This is the first study, to our knowledge, to show that the focal amplification of a gene in Chromosome 8p12, plays a key role in squamous cell lineage specificity of the disease. Our data suggest that genetic activation of BRF2 represents a unique mechanism of SqCC lung tumorigenesis through the increase of Pol III-mediated transcription. It can serve as a marker for lung SqCC and may provide a novel target for therapy. Please see later in the article for the Editors' Summary.