Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Apr 12;7(15):20282-92.
doi: 10.18632/oncotarget.7943.

Repeated observation of immune gene sets enrichment in women with non-small cell lung cancer

Jhajaira M Araujo  1 , Alexandra Prado  1 , Nadezhda K Cardenas  2 , Mayer Zaharia  1 , Richard Dyer  3 , Franco Doimi  3 , Leny Bravo  2 , Luis Pinillos  1 , Zaida Morante  4 , Alfredo Aguilar  1 , Luis A Mas  1 , Henry L Gomez  1 , Carlos S Vallejos  1 , Christian Rolfo  5 , Joseph A Pinto  1
Affiliations

Repeated observation of immune gene sets enrichment in women with non-small cell lung cancer

Jhajaira M Araujo et al. Oncotarget. .

Abstract

There are different biological and clinical patterns of lung cancer between genders indicating intrinsic differences leading to increased sensitivity to cigarette smoke-induced DNA damage, mutational patterns of KRAS and better clinical outcomes in women while differences between genders at gene-expression levels was not previously reported. Here we show an enrichment of immune genes in NSCLC in women compared to men. We found in a GSEA analysis (by biological processes annotated from Gene Ontology) of six public datasets a repeated observation of immune gene sets enrichment in women. "Immune system process", "immune response", "defense response", "cellular defense response" and "regulation of immune system process" were the gene sets most over-represented while APOBEC3G, APOBEC3F, LAT, CD1D and CCL5 represented the top-five core genes. Characterization of immune cell composition with the platform CIBERSORT showed no differences between genders; however, there were differences when tumor tissues were compared to normal tissues. Our results suggest different immune responses in NSCLC between genders that could be related with the different clinical outcome.

Keywords: CIBERSORT; GSEA; gender; immune gene sets; non-small cell lung cancer.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare they have not potential conflicts of interests with this research.

Figures

Figure 1
Figure 1. Immune gene sets enrichment more overrepresented in women
–log10 of P-values are shown in different subsets (A). Enrichment profile generated with GSEA in the gene set “immune process” comparing NSCLC in men vs NSCLC in women shown enrichment in female in smokers (B) and in non-smokers (C).
Figure 1
Figure 1. Immune gene sets enrichment more overrepresented in women
–log10 of P-values are shown in different subsets (A). Enrichment profile generated with GSEA in the gene set “immune process” comparing NSCLC in men vs NSCLC in women shown enrichment in female in smokers (B) and in non-smokers (C).
Figure 2
Figure 2. Enrichment profile and heatmaps generated with comparing the biological process: “REGULATION_OF IMMUNE_SYSTEM_PROCESS” between NSCLC in men vs NSCLC in women
This entichment was observed in subsets of smokers (Figures A, B and C), non-smokers (D) and healthy tissue from non-smokers (E).
Figure 2
Figure 2. Enrichment profile and heatmaps generated with comparing the biological process: “REGULATION_OF IMMUNE_SYSTEM_PROCESS” between NSCLC in men vs NSCLC in women
This entichment was observed in subsets of smokers (Figures A, B and C), non-smokers (D) and healthy tissue from non-smokers (E).
Figure 2
Figure 2. Enrichment profile and heatmaps generated with comparing the biological process: “REGULATION_OF IMMUNE_SYSTEM_PROCESS” between NSCLC in men vs NSCLC in women
This entichment was observed in subsets of smokers (Figures A, B and C), non-smokers (D) and healthy tissue from non-smokers (E).
Figure 3
Figure 3. Relative leukocyte fractions evaluated by CIBERSORT in Affymetrix datasets to infer relative RNA fractions from 22 leukocyte subsets (LM22 signature) in each sample
Shown are the average fractions in each dataset.
See this image and copyright information in PMC

References

    1. Hecht SS. Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst. 1999;91:1194–210. - PubMed
    1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers, Rebelo M, Parkin, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide IARC CancerBase No. 11 [Internet] Lyon, France: International Agency for Research on Cancer; 2013. Available from http://globocan.iarc.fr accessed on 10/July/2015.
    1. Ryberg D, Hewer A, Phillips DH, Haugen A. Different susceptibility to smoking-induced DNA damage among male and female lung cancer patients. Cancer Res. 1994;54:5801–3. - PubMed
    1. Dogan S, Shen R, Ang DC, Johnson ML, D'Angelo SP, Paik PK, Brzostowski EB, Riely GJ, Kris MG, Zakowski MF, Ladanyi M. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res. 2012;18:6169–77. - PMC - PubMed
    1. Radzikowska E, Głaz P, Roszkowski K. Lung cancer in women: age, smoking, histology, performance status, stage, initial treatment and survival. Population-based study of 20,561 cases. Ann Oncol. 2002;13:1087–93. - PubMed

Substances

LinkOut - more resources