Marine omega-3 Polyunsaturated Fatty Acid Intake and Risk of Colorectal Cancer Characterized by Tumor-Infiltrating T Cells
JAMA ONCOLOGY
Authors: Song, Mingyang; Nishihara, Reiko; Cao, Yin; Chun, Eunyoung; Qian, Zhi Rong; Mima, Kosuke; Inamura, Kentaro; Masugi, Yohei; Nowak, Jonathan A.; Nosho, Katsuhiko; Wu, Kana; Wang, Molin; Giovannucci, Edward; Garrett, Wendy S.; Fuchs, Charles S.; Ogino, Shuji; Chan, Andrew T.
Abstract
IMPORTANCE Marine omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid, possess potent immunomodulatory activity and may protect against cancer development. However, evidence relating marine.-3 PUFAs to colorectal cancer (CRC) risk remains inconclusive. OBJECTIVE To test the hypothesis that marine omega-3 PUFA intakemay be associated with lower risk of CRC subsets characterized by immune infiltrate. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort studywas conducted among participants in the Nurses' Health Study (1984-2010) and Health Professionals Follow-up Study (1986-2010). EXPOSURES Intake of marine omega-3 PUFAs. MAIN OUTCOMES AND MEASURES Incidence of CRC characterized by CD3(+), CD8(+), CD45RO (PTPRC)(+), or FOXP3(+) T-cell densities in tumor tissue, measured by immunohistochemical and computer-assisted image analysis. RESULTS Among 173 229 predominantly white participants, 125 172 with 2 895 704 person-years of follow-up provided data about marine omega-3 PUFA intake every 4 years through a validated food frequency questionnaire and followed up for incident CRC evaluation. Of 2504 CRC cases, we documented 614 (252 men, 362 women) from which we could assess T-cell infiltration in the tumor microenvironment. The inverse association of marine omega-3 PUFAs intake with CRC risk differed according to FOXP3(+) T-cell infiltration: compared with intake of less than 0.15 g/d of marine omega-3 PUFAs, intake of at least 0.35 g/d was associated with a multivariable hazard ratio (HR) of 0.57 (95% CI, 0.40-0.81; P <.001 for trend) for FOXP3(+) T-cell-high tumors. In contrast, the HR for FOXP3(+) T-cell-low tumors was 1.14 (95% CI, 0.8-1.60) (P =.77 for trend; P =.01 for heterogeneity). No statistically significant differential association was found for high-density tumors (compared with low-density tumors) according to CD3(+), CD8(+), or CD45RO(+) cell density (P >=.34 for heterogeneity for all comparisons). In functional assays, the suppressive activity of regulatory T cells was approximately 2-fold lower (T-effector-cell proliferation, >= 64% vs 38%) when preincubated with docosahexaenoic acid at 50 mu M, 100 mu M, and 200 mu M concentrations than without docosahexaenoic acid (P <.001 for all comparisons). CONCLUSIONS AND RELEVANCE High marine omega-3 PUFA intake was associated with lower risk of CRC with high-level, but not low-level, FOXP3(+) T-cell density, suggesting a potential role of omega-3 PUFAs in cancer immunoprevention through modulation of regulatory T cells.
Integrated analysis of dysregulated long non-coding RNAs/microRNAs/mRNAs in metastasis of lung adenocarcinoma
JOURNAL OF TRANSLATIONAL MEDICINE
Authors: Li, Lifeng; Peng, Mengle; Xue, Wenhua; Fan, Zhirui; Wang, Tian; Lian, Jingyao; Zhai, Yunkai; Lian, Wenping; Qin, Dongchun; Zhao, Jie
Abstract
BackgroundLung adenocarcinoma (LUAD), largely remains a primary cause of cancer-related death worldwide. The molecular mechanisms in LUAD metastasis have not been completely uncovered.MethodsIn this study, we identified differentially expressed genes (DEGs), miRNAs (DEMs) and lncRNAs (DELs) underlying metastasis of LUAD from The Cancer Genome Atlas database. Intersection mRNAs were used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and co-expression network analysis. In addition, survival analyses of intersection mRNAs were conducted. Finally, intersection mRNAs, miRNAs and lncRNAs were subjected to construct miRNA-mRNA-lncRNA network.ResultsA total of 1015 DEGs, 54 DEMs and 22 DELs were identified in LUAD metastasis and non-metastasis samples. GO and KEGG pathway analysis had proven that the functions of intersection mRNAs were closely related with many important processes in cancer pathogenesis. Among the co-expression interactions network, 22 genes in the co-expression network were over the degree 20. These genes imply that they have connections with many other gene nodes. In addition, 14 target genes (ARHGAP11A, ASPM, HELLS, PRC1, TMPO, ARHGAP30, CD52, IL16, IRF8, P2RY13, PRKCB, PTPRC, SASH3 and TRAF3IP3) were found to be associated with survival in patients with LUAD significantly (log-rank P<0.05). Two lncRNAs (LOC96610 and ADAM6) acting as ceRNAs were identified based on the miRNA-mRNA-lncRNA network.ConclusionsTaken together, the results may provide a novel perspective to develop a multiple gene diagnostic tool for LUAD prognosis, which might also provide potential biomarkers or therapeutic targets for LUAD.