Novel biomarkers that assist in accurate discrimination of squamous cell carcinoma from adenocarcinoma of the lung

Abstract

BackgroundTargeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD). Biomarkers enabling a precise diagnosis are therefore urgently needed.MethodsCap Analysis of Gene Expression (CAGE) is a method used to quantify promoter activities across the whole genome by determining the 5’ ends of capped RNA molecules with next-generation sequencing. We performed CAGE on 97 frozen tissues from surgically resected lung cancers (22 SCC and 75 AD), and confirmed the findings by immunohistochemical analysis (IHC) in an independent group (29 SCC and 45 AD).ResultsUsing the genome-wide promoter activity profiles, we confirmed that the expression of known molecular markers used in IHC for SCC (CK5, CK6, p40 and desmoglein-3) and AD (TTF-1 and napsin A) were different between SCC and AD. We identified two novel marker candidates, SPATS2 for SCC and ST6GALNAC1 for AD, as showing comparable performance and complementary utility to the known markers in discriminating PDSCC and non-lepidic AD. We subsequently confirmed their utility at the protein level by IHC in an independent group.ConclusionsWe identified two genes, SPATS2 and ST6GALNAC1, as novel complemental biomarkers discriminating SCC and AD. These findings will contribute to a more accurate diagnosis of NSCLC, which is crucial for precision medicine for lung cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2792-1) contains supplementary material, which is available to authorized users.

An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1–Positive Lung Adenocarcinomas

“…27 Cap analysis of gene expression (CAGE) data of 97 NSCLC tissue specimens from Japanese patients treated at the Juntendo University Hospital were obtained from the DNA Data Bank of Japan (DDBJ) (JGAD00000000070). 26 Differential expression analysis was performed using edgeR. 4 DNA methylation data generated by Illumina (San Diego, California) Infinium 450K methylation array platform from the TCGA lung adenocarcinoma (LUAD) dataset were processed to obtain b values that represent DNA methylation levels.…”

“…In recent years, genomic alterations, mutation profiles, DNA methylation patterns, and transcriptomic changes in NSCLC have been extensively investigated in large cohorts. 2,3,[26][27][28] In parallel, genome and transcriptome analyses of large panels of NSCLC cell lines have been developed and publicly available. [29][30][31] Previous reports relied on cDNA microarray analyses for transcriptional profiling of NSCLC with neuroendocrine differentiation.…”

Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy

“…Recently, several markers have been studied for the identification of ADC and SqCC. For example, it has been reported that SPATS2 has a sensitivity and specificity of 67% and 100% for the identification of SqCC, and ST6GALNAC1 has a sensitivity and specificity of 67% and 100% for the identification of ADC when using resected tumor tissue [37]. The utility of these candidate biomarkers still needs to be validated in well-designed, large scale studies.…”

In situ cancer diagnosis through online plasmonics

“…Their combined revelation is often needed to ensure and validate the diagnosis through the identification of the cancer type. Recent studies have also pointed out new molecules to distinguish lung cancer subtypes, such as beta-arrestin-1 (El-Khoury et al, 2016) or SPATS2 (Takamochi et al, 2016), among a large number of other markers. Many of them were discovered through new "omics"-based technologies and are of interest for diagnosis, prognosis and/or response to treatments while detected with in vitro assays.…”