Associations between the IASLC/ATS/ERS lung adenocarcinoma classification and EGFR and KRAS mutations

Clay, Tim; Russell, Prudence A.; Do, H.; Sundararajan, Vijaya; Conron, Matthew; Wright, Gavin; Dobrovic, Alexander; Moore, Melissa M.; McLachlan, Sue‐Anne

doi:10.1016/j.pathol.2015.11.002

Cited by 11 publications

(9 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In non‐Asian cohorts, EGFR mutation frequencies of 10%–30% are described in lung adenocarcinomas. KRAS mutations are found in 22–34% of adenocarcinomas, consistent with our observation . The oncogene KRAS activates the RAF/MEK/ERK pathway, leading to upregulation of MYC transcription factor .…”

Section: Discussionsupporting

confidence: 91%

“…KRAS mutations are found in 22-34% of adenocarcinomas, consistent with our observation. 35 The oncogene KRAS activates the RAF/MEK/ERK pathway, leading to upregulation of MYC transcription factor. 36 RAS promotes glucose uptake, glycolytic flux and channeling of intermediates into the pentose phosphate pathway through upregulation of GLUT1 and hexokinase among others.…”

Section: Nsclc Tumor Cell Metabolism In Relation To Histological Subtmentioning

confidence: 99%

See 1 more Smart Citation

Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes

et al. 2019

View full text Add to dashboard Cite

BackgroundBoth hypoxia and oncogenic mutations rewire tumor metabolism. In this study, glucose and glutamine metabolism‐related markers were examined in stage I ‐ resectable stage IIIA non‐small cell lung cancer (NSCLC). Furthermore, expression of metabolism‐related markers was correlated with mutational status to examine mutations associated with rewired tumor metabolism.MethodsMutation analysis was performed for 97 tumors. Glucose and glutamine metabolism‐related marker expression was measured by immunofluorescent staining (protein) and qPCR (mRNA) (n = 81).ResultsGlutamine metabolism‐related markers were significantly higher in adeno‐ than squamous cell NSCLCs. Glucose transporter 1 (GLUT1) protein expression was higher in solid compared to lepidic adenocarcinomas (P < 0.01). In adenocarcinomas, mRNA expression of glutamine transporter SLC1A5 correlated with tumor size (r(p) = 0.41, P = 0.005). Furthermore, SLC1A5 protein expression was significantly higher in adenocarcinomas with worse pTNM stage (r(s) = 0.39, P = 0.009). EGFR‐mutated tumors showed lower GLUT1 protein (P = 0.017), higher glutaminase 2 (GLS2) protein (P = 0.025) and higher GLS2 mRNA expression (P = 0.004), compared to EGFR wild‐type tumors. GLS mRNA expression was higher in KRAS‐mutated tumors (P = 0.019). TP53‐mutated tumors showed higher GLUT1 expression (P = 0.009).ConclusionsNSCLC is a heterogeneous disease, with differences in mutational status and metabolism‐related marker expression between adeno‐ and squamous cell NSCLCs, and also within adenocarcinoma subtypes. GLUT1 and SLC1A5 expression correlate with aggressive tumor behavior in adenocarcinomas but not in squamous cell NSCLCs. Therefore, these markers could steer treatment modification for subgroups of adenocarcinoma patients. TP53, EGFR and KRAS mutations are associated with expression of glucose and glutamine metabolism‐related markers in NSCLC.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Nsclc Tumor Cell Metabolism In Relation To Histological Subtmentioning

confidence: 99%

Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Since radiotherapy agents can effectively induce apoptosis through generation of ROS [97] it was observed that specific PI3K inhibitor such as NVP-BKM120 can be used in SqCC to decrease Nrf2 protein levels and sensitize NFE2L2 or KEAP1 -mutant cells to radiation [94]. KRAS gene mutations occur approximately in 20–30% of NSCLCs and confer to cancer cells resistance and survival [98, 99]. Promoter analysis showed that a TPA response element (TRE) located in exon1 of NFE2L2 gene was activated by Kras.…”

Section: Nrf2 Signalingmentioning

confidence: 99%

Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

Sparaneo

Fabrizio

Muscarella

2016

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

The transcription factor Nrf2 (NF-E2 related factor 2) is a master regulator of the cell antioxidant response associated with tumor growth and resistance to cytotoxic treatments. In particular, Nrf2 induces upregulation of cytoprotective genes by interacting with the closely situated AREs (Antioxidant Response Elements) in response to endogenous or exogenous stress stimuli and takes part to several oncogenic signaling pathways. Among these, the crosstalk with Notch pathway has been shown to enhance cytoprotection and maintenance of cellular homeostasis, tissue organization by modulating cell proliferation kinetics, and stem cell self-renewal in several organs. The role of Notch and Nrf2 related pathways in tumorigenesis is highly variable and when they are both abnormally activated they can synergistically cause neoplastic proliferation by promoting cell survival, differentiation, invasion, and metastases. NFE2L2, KEAP1, and NOTCH genes family appear in the list of significantly mutated genes in tumors in both combined and individual sets, supporting the crucial role that the aberrant Nrf2-Notch crosstalk might have in cancerogenesis. In this review, we summarize current knowledge about the alterations of Nrf2 and Notch pathways and their reciprocal transcriptional regulation throughout tumorigenesis and progression of lung tumors, supporting the potentiality of putative biomarkers and therapeutic targets.

show abstract

“…Mutation of EGFR, the most common targetable driver mutation in advanced lung adenocarcinoma with the mutation rate varying between 43.5 and 76.6% in Asian cohorts and between 9.6 and 29.8% in non-Asian cohorts, has attracted increasing attention (44). Numerous studies have detailed the close association between lung cancer invasion and EGFR mutation status (45)(46)(47).…”

Section: Mir-135b Expression In Adc (T/n) ---------------------------mentioning

confidence: 99%

Peripheral lung adenocarcinomas harboring epithelial growth factor receptor mutations with microRNA‑135b overexpression are more likely to invade visceral pleura

Wang

Zha

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

Abstract. Lung adenocarcinoma, characterized by its early and aggressive local invasion and high metastatic potential, is the most frequently observed histological type of non-small-cell lung cancer (NSCLC). Visceral pleural invasion (VPI) caused by peripheral lung adenocarcinomas is closely associated with the poor prognosis of patients with NSCLC. The association between VPI and some clinicopathological characteristics has been observed in the past few decades. However, the molecular mechanism of VPI in lung adenocarcinomas is unknown. In the present, the expression level of microRNA (miR-)135b and epidermal growth factor receptor (EGFR) mutations using the reverse transcription-quantitative polymerase chain reaction and DNA sequencing, respectively. In addition, the present study aimed at exploring the association between the miR-135b level, EGFR mutations and VPI in peripheral lung adenocarcinoma. The results of the present study demonstrated that miR-135b was significantly upregulated in lung adenocarcinoma compared with adjacent normal tissue and positively associated EGFR mutations in peripheral lung adenocarcinoma. Furthermore, it was identified that lung adenocarcinomas with EGFR mutations and miR-135b overexpression were more likely to invade visceral pleura. Taken together, these findings indicate that miR-135b overexpression is positively associated with mutations to EGFR, which may promote the development of peripheral lung adenocarcinomas by the formation of VPI. This indicates that the two factors may serve as prognostic markers and molecular targets for the treatment of peripheral lung adenocarcinomas.

show abstract

Associations between the IASLC/ATS/ERS lung adenocarcinoma classification and EGFR and KRAS mutations

Cited by 11 publications

References 29 publications

Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes

Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes

Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

Peripheral lung adenocarcinomas harboring epithelial growth factor receptor mutations with microRNA‑135b overexpression are more likely to invade visceral pleura

Contact Info

Product

Resources

About