scholarly journals A comparative microarray analysis identifies a conserved gene expression signature between airway injury and lung cancer

2016 ◽  
Author(s):  
Adam Giangreco

AbstractLung squamous cell carcinoma (SqCC) accounts for 30% of lung cancers, with over 400,000 deaths per year worldwide. Although evidence suggests that chronic lung injury drives carcinogenesis, a comprehensive understanding of this process remains elusive. Here, I used a comparative microarray analysis to identify gene expression differences shared between airway injury and squamous lung cancer. Of the 667 genes that exhibited differential expression following murine polidocanol and SO2 injury, 40.6% were additionally dysregulated in human SqCC. Among these, 150 genes were consistently upregulated and 54 downregulated relative to all controls. Examples included genes associated with increased cell cycling, aberrant cytokinesis and DNA repair, and enhanced tumour cell invasion and metastases. For 88.2% of identified genes, altered expression was associated with increased SqCC progression and patient mortality. These results establish a novel gene expression signature linking airway injury and lung cancer pathogenesis.

2015 ◽  
Vol 16 (12) ◽  
pp. 11465-11481 ◽  
Author(s):  
Xi Wang ◽  
Yujie Ning ◽  
Feng Zhang ◽  
Fangfang Yu ◽  
Wuhong Tan ◽  
...  

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 69-69
Author(s):  
Melissa Rotunno ◽  
Nan Hu ◽  
Hua Su ◽  
Chaoyu Wang ◽  
Pier Alberto Bertazzi ◽  
...  

69 Background: Accurate blood-based biomarker for early cancer detection could be an easier and more convenient screening option than monitoring the target organ via tissue or imaging. We recently identified and validated eight genetic biomarkers of early-stage lung adenocarcinoma detectable in both peripheral whole blood (PWB) and lung tissue of smokers. Since biomarkers distinguishing benign disease versus lung malignancy across all cell types are needed in the diagnostic clinical setting, it is important to test the identified biomarkers in other lung cancer histologies, particularly in squamous cell carcinoma (SQCC), the second most common lung cancer histology after adenocarcinoma (AD). Methods: Using Real-Time Quantitative PCR (qRT-PCR), we measured mRNA levels for the eight candidate genes in PWB of 48 randomly sampled stage I SQCC cases, in addition to previously analyzed 82 AD cases and 130 age, sex, and smoking frequency matched healthy controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study. The qRT-PCR data were analyzed using the 2-ΔΔCtmethod to compare SQCC cases with controls. The area under the receiver operating characteristic curve (AUC) was computed to assess the predictive accuracy of the candidate biomarkers in SQCC separately, and in SQCC and AD together. Results: Expression of TGFBR3, RUNX3, TRGC2, TRGV9, TARP, and TSTA3 genes, significantly differentiated SQCC cases versus controls, while ACP1 and VCAN gene expression did not. The eight genes combined discriminated patients with lung cancer from healthy controls with similarly high accuracy in SQCC and overall (AUC = 0.80 ± 0.1). RUNX3 showed the highest single gene accuracy for SQCC (AUC = 0.78). Conclusions: We showed that the previously identified gene expression signature of early-stage lung AD also differentiated early stage SQCC from healthy controls and demonstrated its sensitivity and specificity as a potential diagnostic lung cancer biomarker. Since lung cancer is the most common cause of cancer mortality worldwide and current smokers are at very high risk, our smoking-specific findings, if confirmed and translated into screening approaches, have the potential to impact public health.


PLoS Medicine ◽  
2006 ◽  
Vol 3 (12) ◽  
pp. e467 ◽  
Author(s):  
Yan Lu ◽  
William Lemon ◽  
Peng-Yuan Liu ◽  
Yijun Yi ◽  
Carl Morrison ◽  
...  

Oncogene ◽  
2004 ◽  
Vol 24 (7) ◽  
pp. 1212-1219 ◽  
Author(s):  
Jiangting Hu ◽  
Fabrizio Bianchi ◽  
Mary Ferguson ◽  
Alfredo Cesario ◽  
Stefano Margaritora ◽  
...  

2006 ◽  
Vol 66 (4) ◽  
pp. 1956-1963 ◽  
Author(s):  
Yan Lu ◽  
Ruisheng Yao ◽  
Ying Yan ◽  
Yian Wang ◽  
Yukihiko Hara ◽  
...  

The Prostate ◽  
2002 ◽  
Vol 51 (3) ◽  
pp. 189-200 ◽  
Author(s):  
Jun Luo ◽  
Thomas Dunn ◽  
Charles Ewing ◽  
Jurga Sauvageot ◽  
Yidong Chen ◽  
...  

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