Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma

Xiao, Jian; Lu, Xiaoxiao; Chen, Xi; Zou, Yong; Liu, Aibin; Li, Wei; He, Bixiu; He, Shuya; Chen, Qiong

doi:10.18632/oncotarget.17606

Cited by 63 publications

(48 citation statements)

References 62 publications

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“…30). Importantly, KRT5, KRT6A, KRT6B, and DSG3 were recently highlighted through ROC curves as biomarkers to differentiate lung adenocarcinoma from lung squamous cell cancer (31). Indeed, our analysis showed that KRT5, KRT6A, KRT6B, and DSG3 were highly expressed in LuCaP 173.2 squamous pearl cells compared with surrounding DNPC tissue ( Figure 5B).…”

Section: Resultsmentioning

confidence: 51%

Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer

Labrecque

Coleman

Brown

et al. 2019

Journal of Clinical Investigation

292

449

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resulting in the suppression of AR target genes and clinical remissions that generally last several years (1). However, ADT is not curative. PC recurs as castration-resistant prostate cancer (CRPC), typically with reactivated AR signaling. Second-generation AR pathway inhibitors (ARIs), such as enzalutamide (ENZ) and abiraterone (ABI), were designed to further repress AR signaling and are primarily used to treat CRPC. Although these agents extend survival, durable complete responses are rare and these therapies also eventually fail (2, 3). Typically, the vast majority of metastatic CRPC (mCRPC) tumors progress with rising prostate-specific antigen (PSA/KLK3) levels despite standard of care treatment. Moreover, most mCRPC tumors are adenocarcinomas, which have robust AR program activity (4). Though rigorous epidemiological data are lacking, recent studies report that a substantial number of mCRPC tumors progressing on ARIs have lost AR signaling (5). Paralleling increased use of ARIs has been an increase in the proportion of treatment-resistant CRPC metastases that have AR-null phenotypes, i.e. tumors with diffuse small cell or neuroendocrine (NE) characteristics (SCNPC) or the recently described double-negative (DNPC) phenotype that lacks both NE and AR activity (5). A contemporary study evaluating the histology and molecular characteristics of 202 men with mCRPC found that 17% of the evaluable tumors were classified as SCNPC and this phenotype was associated with short-Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with diverse drivers of disease progression and mechanisms of therapeutic resistance. We conducted deep phenotypic characterization of CRPC metastases and patient-derived xenograft (PDX) lines using whole-genome RNA sequencing, gene set enrichment analysis, and immunohistochemistry. Our analyses revealed 5 mCRPC phenotypes based on the expression of well-characterized androgen receptor (AR) or neuroendocrine (NE) genes: AR-high tumors (ARPC), AR-low tumors (ARLPC), amphicrine tumors composed of cells coexpressing AR and NE genes (AMPC), double-negative tumors (i.e., AR-/NE-; DNPC), and tumors with small cell or NE gene expression without AR activity (SCNPC). RE1 silencing transcription factor (REST) activity, which suppresses NE gene expression, was lost in AMPC and SCNPC PDX models. However, knockdown of REST in cell lines revealed that attenuated REST activity drives the AMPC phenotype but is not sufficient for SCNPC conversion. We also identified a subtype of DNPC tumors with squamous differentiation and generated an encompassing 26-gene transcriptional signature that distinguished the 5 mCRPC phenotypes. Together, our data highlight the central role of AR and REST in classifying treatment-resistant mCRPC phenotypes. These molecular classifications could potentially guide future therapeutic studies and clinical trial design.

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Section: Resultsmentioning

confidence: 51%

Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer

Labrecque

Coleman

Brown

et al. 2019

Journal of Clinical Investigation

292

449

View full text Add to dashboard Cite

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“…Among the most significant shared genes that are associated with COVID-19 are KRT6B and TNFAIP3. Keratin 6B (KRT6B) is a type II cytokeratin, which is an important biomarker for lung adenocarcinoma (Xiao et al 2017). These genes are known as a virus-induced host factors that control the recruitment of Tcells and correlates to chronic virus infections ).…”

Section: Given the Important Association Between Heparin-binding Go Amentioning

confidence: 99%

The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1

Alsamman

Zayed

2020

Preprint

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COVID-19 pandemic is a global crisis that threatens our way of life. As of April 29, 2020, COVID-19 has claimed more than 200,000 lives, with a global mortality rate of~7% and recovery rate of~30%. Understanding the interaction of cellular targets to the SARS-CoV2 infection is crucial for therapeutic development. Therefore, the aim of this study was to perform a comparative analysis of transcriptomic signatures of infection of COVID-19 compared to different respiratory viruses (Ebola, H1N1, MERS-CoV, and SARS-CoV), to determine unique anti-COVID1-19 gene signature. We identified for the first time molecular pathways for Heparin-binding, RAGE, miRNA, and PLA2 inhibitors, to be associated with SARS-CoV2 infection. The NRCAM and SAA2 that are involved in severe inflammatory response, and FGF1 and FOXO1genes, which are associated with immune regulation, were found to be associated with a cellular gene response to COVID-19 infection. Moreover, several cytokines, most significantly the IL-8, IL-6, demonstrated key associations with COVID-19 infection. Interestingly, the only response gene that was shared between the five viral infections was SERPINB1. The PPI study sheds light on genes with high interaction activity that COVID-19 shares with other viral infections. The findings showed that the genetic pathways associated with Rheumatoid arthritis, AGE-RAGE signaling system, Malaria, Hepatitis B, and Influenza A were of high significance. We found that the virogenomic transcriptome of infection, gene modulation of host antiviral responses, and GO terms of both COVID-19 and Ebola are more similar compared to SARS, H1N1, and MERS. This work compares the virogenomic signatures of highly pathogenic viruses and provides valid targets for potential therapy against COVID-19.

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“…Likewise, the keratin 6B (KRT6B) gene encodes for a type II keratin that is normally present in mammalian epithelial cells and is rapidly induced in human keratinocytes after skin wounding [26]. KRT6B has been identified as a potential biomarker for differentiating between lung adenocarcinoma and lung squamous cell carcinoma, and its increased expression is associated with lower disease-free survival rates in young breast cancer patients [27,28]. Mutations in the KRT6B gene result in an autosomal dominant skin disorder known as pachyonychia congenita, which involves plantar keratoderma and pain alongside thickened toenails [29].…”

Section: Discussionmentioning

confidence: 99%

Epigenome-wide analysis of common warts reveals aberrant promoter methylation

et al. 2020

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Epigenetic alteration of host DNA is a common occurrence in both low-and high-risk human papillomavirus (HPV) infection. Although changes in promoter methylation have been widely studied in HPV-associated cancers, they have not been the subject of much investigation in HPV-induced warts, which are a temporary manifestation of HPV infection. The present study sought to examine the differences in promoter methylation between warts and normal skin. To achieve this, DNA was extracted from 24 paired wart and normal skin samples and inputted into the Infinium MethylationEPIC BeadChip microarray. Differential methylation analysis revealed a clear pattern of hyper-and hypomethylation in warts compared to normal skin, and the most differentially methylated promoters were found within the EIF3EP2, CYSLTR1, C10orf99, KRT6B, LAMA4, and H3F3B genes as well as the C9orf30 pseudogene. Moreover, pathway analysis showed that the H3F3A, CDKN1A, and MAPK13 genes were the most common regulators among the most differentially methylated promoters. Since the tissue samples were excised from active warts, however, this differential methylation could either be a cellular response to HPV infection or an HPV-driven process to establish the wart and/or promote disease progression. Conclusively, it is apparent that HPV infection alters the methylation status of certain genes to possibly initiate the formation of a wart and maintain its presence.

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Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma

Cited by 63 publications

References 62 publications

Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer

Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer

The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1

Epigenome-wide analysis of common warts reveals aberrant promoter methylation

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