Gene expression–based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study

Shedden, Kerby; Taylor, Jeremy M. G.; Enkemann, Steven A.; Tsao, Ming‐Sound; Yeatman, Timothy J.; Gerald, William L.; Eschrich, Steven; Jurišica, Igor; Giordano, Thomas J.; Misek, David E.; Chang, Andrew C.; Zhu, Chang-Qi; Strumpf, Daniel; Hanash, Samir M.; Shepherd, Frances A.; Ding, Keyue; Seymour, Lesley; Naoki, Katsuhiko; Pennell, Nathan A.; Weir, Barbara A.; Verhaak, Roeland; Ladd‐Acosta, Christine; Golub, Todd R.; Gruidl, Michael E.; Sharma, Anupama; Szőke, János; Zakowski, Maureen F.; Rusch, Valerie W.; Kris, Mark G.; Viale, Agnès; Motoi, Noriko; Travis, William D.; Conley, Barbara A.; Seshan, Venkatraman; Meyerson, Matthew; Kuick, Rork; Dobbin, Kevin K.; Lively, Tracy; Jacobson, James W.; Beer, David G.

doi:10.1038/nm.1790

Cited by 958 publications

(755 citation statements)

References 16 publications

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“…33,34 Modulation and interactions of these cytokine productions may be pivotal for the control of inflammation and tumor progression. Besides, recent studies using gene expression assays have been used to predict the survival of patients with lung and colorectal carcinoma 35,36 and have proven to be more precise in the classification of the disease stage than the current systems. Richardsen 38 also found high expression of COX-2, tumor growth factor-b and Ki67 in metastatic primary prostate carcinoma compared with non-metastatic cancers.…”

Section: Discussionmentioning

confidence: 99%

IL-10 polymorphisms and prostate cancer risk: a meta-analysis

Shao

et al. 2011

Prostate Cancer Prostatic Dis

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Evidence is accumulating that chronic inflammation may have an important role in prostate cancer (PCa). Three common polymorphisms in the promoter of interleukin-10 (IL-10) gene, À1082 A4G, À819 C4T and À592 C4A, have been implicated to alter the risk of PCa, but the results of relative studies are inconclusive or controversial. To derive a more precise estimation of the relationship, we performed an updated meta-analysis on the basis of 10 studies. A comprehensive search was conducted to examine all the eligible studies of IL-10 polymorphism and PCa risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) give a sense of the precision of the estimate. Overall, there were no significant associations between increased risk of PCa and IL-10 À1082 A4G, À819 C4T and À592 C4A polymorphisms. However, meta-analysis suggested that IL-10 À819 C4T and À592 C4A polymorphisms might be modestly associated with PCa aggressiveness (T versus C, OR ¼ 1.162, 95% CI: 1.035-1.305, P ¼ 0.011; A versus C, OR ¼ 1.131, 95% CI: 1.012-1.264, P ¼ 0.030; respectively). IL-10 À819 C4T and À592 C4A polymorphisms might impact PCa progression. Variant alleles at both À819 and À592 were modestly associated with advanced stages of PCa. Additional well-designed studies are warranted to validate these findings.

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Section: Discussionmentioning

confidence: 99%

IL-10 polymorphisms and prostate cancer risk: a meta-analysis

Shao

et al. 2011

Prostate Cancer Prostatic Dis

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“…We queried Gene Expression Omnibus (GEO) with the keyword “lung” and with the platform set to “GPL570” or “GPL96,” and then selected datasets with a sample size of more than 30. As a result, we got six datasets on platform GPL570, including GSE10245 (n = 40), 34 GSE19188 (n = 110), 35 GSE30219 (n = 83), 36 GSE31210 (n = 224), 37,38 GSE37745 (n = 91), 39 and GSE50081 (n = 128), 40 and five datasets on platform GPL96, including GSE10072 (n = 107), 41 GSE14814 (n = 71), 42 GSE31547 (n = 50), 43 GSE68465 (n = 353), 44 and GSE7670 (n = 54). 45 Detailed information about the datasets is presented in Table 1; the sample numbers are the result of removing patients treated with chemotherapy or radiotherapy.…”

Section: Methodsmentioning

confidence: 99%

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

et al. 2018

OncoImmunology

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Tobacco smoking causes DNA damages in epithelial cells and immune dysfunction in the lung, which collectively contribute to lung carcinogenesis and progression. However, potential mechanisms by which tumor-infiltrating immune cells contribute to lung cancer survival and their differential contributions in ever-smokers and never-smokers are not well studied. Here, we performed integrative analysis of 11 lung cancer gene-expression datasets, including 1,111 lung adenocarcinomas and 200 adjacent normal lung samples. Distinct pathways were altered in lung carcinogenesis in ever-smokers and never-smokers. Never-smoker patients had a better outcome than ever-smoker patients. We characterized compositional patterns of 21 types of immune cells in lung adenocarcinomas and revealed the complex association between immune cell composition and clinical outcomes. Interestingly, we found two subsets of immune cells, mast cells and CD4+ memory T cells, which had completely opposite associations with outcomes in resting and activated status. We further discovered that several chemokines and their associated receptors (e.g., CXCL11-CX3CR1 axis) were selectively altered in lung tumors in response to cigarette smoking and their abundances showed stronger correlation with fractions of these immune subsets in ever-smokers than never-smokers. The status switched from the resting to activated forms in mast cells and CD4+ memory T cells might manifest some important processes induced by cigarette smoking during tumor development and progression. Our findings suggested that aberrant activation of mast cells and CD4+ memory T cells plays crucial roles in cigarette smoking-induced immune dysfunction in the lung, which contributes to tumor development and progression.

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“…To further validate the relevance of this classification in primary tumors, we performed hierarchical cluster analysis using publicly available data of 442 primary lung adenocarcinoma cases, 37 using the genes selectively expressed in Group I and Group II. As shown in Figure 4A, primary lung adenocarcinoma cases were divided into three clusters (Cluster A, B, and C), reflecting the intertumoral heterogeneity of primary tumors as compared to cell lines.…”

Section: Hierarchical Cluster Analysis Of Primary Tumorsmentioning

confidence: 99%

Co-Activation of Epidermal Growth Factor Receptor and c-MET Defines a Distinct Subset of Lung Adenocarcinomas

Matsubara

Ishikawa

Oguni

et al. 2010

The American Journal of Pathology

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Epidermal growth factor receptor (EGFR) and MET are molecular targets for lung cancer treatment. The relationships between expression, activation, and gene abnormalities of these two targets are currently unclear. Here, we demonstrate that a panel of 40 lung cancer cell lines could be classified into two groups. Group I was characterized by (1) high phosphorylations of MET and EGFR, (2) frequent mutation or amplification of EGFR, MET, and human epidermal growth factor receptor-2 (HER2), (3) high expressions of bronchial epithelial markers (thyroid transcription factor-1 (TTF-1), MUC1, and Cytokeratin 7 (CK7)); and (4) high expressions of MET, human epidermal growth factor receptor-3, E-cadherin, cyclooxygenase-2, and laminin gamma2. In contrast, Group II exhibited little or no phosphorylation of MET and EGFR; no mutation or amplification of EGFR, MET, and HER2; were triple-negative for TTF-1, MUC1, and CK7; and showed high expressions of vimentin, fibroblast growth factor receptor-1, and transcription factor 8. Importantly, Group I was more sensitive to gefitinib and more resistant to cisplatin and paclitaxel than Group II. The clinical relevance was confirmed in publicly available data on 442 primary lung adenocarcinoma patients; survival benefits by postoperative chemotherapy were seen in only patients with tumors corresponding to Group II. Overall, co-activation of EGFR and MET defines a distinct subgroup of lung carcinoma with characteristic genetic abnormalities, gene expression pattern , and response to chemotherapeutic reagents. (Am J

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Gene expression–based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study

Cited by 958 publications

References 16 publications

IL-10 polymorphisms and prostate cancer risk: a meta-analysis

IL-10 polymorphisms and prostate cancer risk: a meta-analysis

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

Co-Activation of Epidermal Growth Factor Receptor and c-MET Defines a Distinct Subset of Lung Adenocarcinomas

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