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Molecular Changes of Lung Malignancy in HIV Infection.

ABSTRACT: Malignancy of the lung is a major source of morbidity and mortality in persons with human immunodeficiency virus infection; as the most prevalent non-acquired immunodeficiency syndrome-defining malignancy, it represents an important and growing problem confronting HIV-infected patients. To evaluate the molecular changes of lung malignancy in HIV infection, we analyzed differential gene expression profiles and screened for early detection biomarkers of HIV-associated lung cancer using Affymetrix arrays and IPA analysis. A total of 59 patients were diagnosed with HIV-associated lung cancer from Jan 2010 to May 2018. The primary outcome was a significant difference in survival outcome between stages III-IV (10.46 ± 1.87 months) and I-II (17.66 ± 2.88 months). We identified 758 differentially expressed genes in HIV-associated lung cancer. The expression levels of SIX1 and TFAP2A are specifically increased in HIV-associated lung cancer and are associated with poorly differentiated tumor tissue. We also found decreased ADH1B, INMT and SYNPO2 mRNA levels in HIV lung cancer. A comprehensive network and pathway analysis of the dysregulated genes revealed that these genes were associated with four network functions and six canonical pathways relevant to the development of HIV-associated lung cancer. The molecular changes in lung malignancy may help screen the growing population of HIV patients who have or will develop this malignancy.

SUBMITTER: Zheng J

PROVIDER: S-EPMC6120915 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Many studies have explored changes in the gut microbiome associated with HIV infection, but the consistent pattern of changes has not been clarified. Men who have sex with men (MSM) are very likely to be an independent influencing factor of the gut microbiome, but relevant research is still lacking. Methods: We conducted a meta-analysis by screening 12 published studies of 16S rRNA gene amplicon sequencing of gut microbiomes related to HIV/AIDS (six of these studies contain data that is relevant and available to MSM) from NCBI and EBI databases. The analysis of gut microbiomes related to HIV infection status and MSM status included 1,288 samples (HIV-positive (HIV+) individuals, n = 744; HIV-negative (HIV-) individuals, n = 544) and 632 samples (MSM, n = 328; non-MSM, n = 304), respectively. The alpha diversity indexes, beta diversity indexes, differentially enriched genera, differentially enriched species, and differentially enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways related to gut microbiomes were calculated. Finally, the overall trend of the above indicators was evaluated. Results: Our results indicate that HIV+ status is associated with decreased alpha diversity of the gut microbiome. MSM status is an important factor that affects the study of HIV-related gut microbiomes; that is, MSM are associated with alpha diversity changes in the gut microbiome regardless of HIV infection, and the changes in the gut microbiome composition of MSM are more significant than those of HIV+ individuals. A consistent change in Bacteroides caccae, Bacteroides ovatus, Bacteroides uniformis, and Prevotella stercorea was found in HIV+ individuals and MSM. The differential expression of the gut microbiome may be accompanied by changes in functional pathways of carbohydrate metabolism, amino acid metabolism, and lipid Metabolism. Conclusions: This study shows that the changes in the gut microbiome are related to HIV and MSM status. Importantly, MSM status may have a far greater impact on the gut microbiome than HIV status.

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Molecular Changes of Lung Malignancy in HIV Infection.

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