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Panâ cancer genomic analyses reveal prognostic and immunogenic features of the tumor melatonergic microenvironment across 14 solid cancer types
dc.contributor.authorLv, Jia‐wei
dc.contributor.authorZheng, Zi‐qi
dc.contributor.authorWang, Zi‐xian
dc.contributor.authorZhou, Guan‐qun
dc.contributor.authorChen, Lei
dc.contributor.authorMao, Yan‐ping
dc.contributor.authorLin, Ai‐hua
dc.contributor.authorReiter, Russel J.
dc.contributor.authorMa, Jun
dc.contributor.authorChen, Yu‐pei
dc.contributor.authorSun, Ying
dc.date.accessioned2019-03-11T15:34:52Z
dc.date.available2020-06-01T14:50:01Zen
dc.date.issued2019-04
dc.identifier.citationLv, Jia‐wei ; Zheng, Zi‐qi ; Wang, Zi‐xian ; Zhou, Guan‐qun ; Chen, Lei; Mao, Yan‐ping ; Lin, Ai‐hua ; Reiter, Russel J.; Ma, Jun; Chen, Yu‐pei ; Sun, Ying (2019). "Panâ cancer genomic analyses reveal prognostic and immunogenic features of the tumor melatonergic microenvironment across 14 solid cancer types." Journal of Pineal Research 66(3): n/a-n/a.
dc.identifier.issn0742-3098
dc.identifier.issn1600-079X
dc.identifier.urihttps://hdl.handle.net/2027.42/148219
dc.description.abstractWe performed comprehensive genomic analyses of the melatonergic system within the tumor microenvironment and their clinical relevance across a broad spectrum of solid tumors. RNAâ seq data from The Cancer Genome Atlas (TCGA) of 14 solid tumors representing 6658 human samples were analyzed. The tumor melatonergic system was characterized by the rates of melatonin synthesis and metabolism using a twoâ gene expression model (melatonin synthesis/metabolism Index). We calculated three indexes according to different melatonin metabolism isoenzymes (Indexâ I [ASMT:CYP1A1], Indexâ II [ASMT:CYP1A2], and Indexâ III [ASMT:CYP1B1]). Samples of each cancer type were classified into two subgroups (high vs low) based on median values. Clinical outcomes, mutational burden, and neoepitope abundance were analyzed and compared. We found that the ability of the tumor microenvironment to synthesize and accumulate melatonin varied across cancer types and negatively correlated with tumor burden. Kaplanâ Meier survival analyses and multivariable modeling showed that the three indexes played different roles across different cancers and harbored prognostic values in breast cancer (adjusted hazard ratio [AHR]Indexâ II = 0.65 [0.44â 0.97]; P = 0.03), cervical cancer (AHRIndexâ I = 0.62 [0.39â 0.98]; P = 0.04), lung squamous cell carcinoma (AHRIndexâ III = 0.75 [0.56â 0.99]; P = 0.04), melanoma (AHRIndexâ I = 0.74 [0.55â 0.98]; P = 0.04), and stomach adenocarcinoma (AHRIndexâ III = 0.68 [0.41â 0.94]; P = 0.02). We further investigated its clinical relevance with tumor immunogenic features (mutational burden and neoantigen abundance), which may predict immunotherapy benefits. We observed significant negative correlations with mutational burden in the majority of tumors (P < 0.05), except cervical cancer, pancreatic adenocarcinoma, and thyroid carcinoma. Our study provides a systematic overview of the oncostatic values of the melatonergic system and highlights the utilization of this simple and promising gene signature as a prognosticator and potential predictor of response to immunotherapy.
dc.publisherWiley Periodicals, Inc.
dc.subject.otherpanâ cancer analyses
dc.subject.othertumor microenvironment
dc.subject.otherneoantigen abundance
dc.subject.othermutational burden
dc.subject.othermolecular marker
dc.subject.othermelatonergic system
dc.subject.otherprognosis
dc.titlePanâ cancer genomic analyses reveal prognostic and immunogenic features of the tumor melatonergic microenvironment across 14 solid cancer types
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelInternal Medicine and Specialties
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/148219/1/jpi12557.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/148219/2/jpi12557_am.pdf
dc.identifier.doi10.1111/jpi.12557
dc.identifier.sourceJournal of Pineal Research
dc.identifier.citedreferenceHong Y, Won J, Lee Y, et al. Melatonin treatment induces interplay of apoptosis, autophagy, and senescence in human colorectal cancer cells. J Pineal Res. 2014; 56: 264 â 274.
dc.identifier.citedreferenceKinker GS, Obaâ Shinjo SM, Carvalhoâ Sousa CE, et al. Melatonergic systemâ based twoâ gene index is prognostic in human gliomas. J Pineal Res. 2016; 60: 84 â 94.
dc.identifier.citedreferenceSchumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015; 348: 69 â 74.
dc.identifier.citedreferenceRizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PDâ 1 blockade in nonâ small cell lung cancer. Science. 2015; 348: 124 â 128.
dc.identifier.citedreferenceCerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012; 2: 401 â 404.
dc.identifier.citedreferenceGao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013; 6: pl1.
dc.identifier.citedreferenceCancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012; 489: 519 â 525.
dc.identifier.citedreferencePalmer C, Diehn M, Alizadeh AA, et al. Cellâ type specific gene expression profiles of leukocytes in human peripheral blood. BMC Genom. 2006; 7: 115.
dc.identifier.citedreferenceOck CY, Keam B, Kim S, et al. Panâ cancer immunogenomic perspective on the tumor microenvironment based on PDâ L1 and CD8 Tâ cell infiltration. Clin Cancer Res. 2016; 22: 2261 â 2270.
dc.identifier.citedreferenceRooney MS, Shukla SA, Wu CJ, et al. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell. 2015; 160: 48 â 61.
dc.identifier.citedreferenceSubramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledgeâ based approach for interpreting genomeâ wide expression profiles. Proc Natl Acad Sci USA. 2005; 102: 15545 â 15550.
dc.identifier.citedreferenceCardinali DP, Esquifino AI, Srinivasan V, et al. Melatonin and the immune system in aging. NeuroImmunoModulation. 2008; 15: 272 â 278.
dc.identifier.citedreferenceNasrabadi NN, Ataee R, Abediankenari S, et al. Expression of MT2 receptor in patients with gastric adenocarcinoma and its relationship with clinicopathological features. J Gastrointest Cancer. 2014; 45: 54 â 60.
dc.identifier.citedreferenceCalvo JR, Gonzalezâ Yanes C, Maldonado MD. The role of melatonin in the cells of the innate immunity: a review. J Pineal Res. 2013; 55: 103 â 120.
dc.identifier.citedreferenceMiller SC, Pandiâ Perumal SR, Esquifino AI, et al. The role of melatonin in immunoâ enhancement: potential application in cancer. Int J Exp Pathol. 2006; 87: 81 â 87.
dc.identifier.citedreferencePoplawski T, Chojnacki C, Czubatka A, et al. Helicobacter pylori infection and antioxidants can modulate the genotoxic effects of heterocyclic amines in gastric mucosa cells. Mol Biol Rep. 2013; 40: 5205 â 5212.
dc.identifier.citedreferenceErdemli HK, Akyol S, Armutcu F, et al. Melatonin and caffeic acid phenethyl ester in the regulation of mitochondrial function and apoptosis: The basis for future medical approaches. Life Sci. 2016; 148: 305 â 312.
dc.identifier.citedreferenceMendivilâ Perez M, Sotoâ Mercado V, Guerraâ Librero A, et al. Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function. J Pineal Res. 2017; 63: e12415.
dc.identifier.citedreferenceWu SM, Lin WY, Shen CC, et al. Melatonin set out to ER stress signaling thwarts epithelial mesenchymal transition and peritoneal dissemination via calpainâ mediated C/EBPbeta and NFkappaB cleavage. J Pineal Res. 2016; 60: 142 â 154.
dc.identifier.citedreferenceChang I, Mitsui Y, Kim SK, et al. Cytochrome P450 1B1 inhibition suppresses tumorigenicity of prostate cancer via caspaseâ 1 activation. Oncotarget. 2017; 8: 39087 â 39100.
dc.identifier.citedreferenceMitsui Y, Chang I, Fukuhara S, et al. CYP1B1 promotes tumorigenesis via altered expression of CDC20 and DAPK1 genes in renal cell carcinoma. BMC Cancer. 2015; 15: 942.
dc.identifier.citedreferenceLissoni P, Chilelli M, Villa S, et al. Five years survival in metastatic nonâ small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial. J Pineal Res. 2003; 35: 12 â 15.
dc.identifier.citedreferenceWang YM, Jin BZ, Ai F, et al. The efficacy and safety of melatonin in concurrent chemotherapy or radiotherapy for solid tumors: a metaâ analysis of randomized controlled trials. Cancer Chemother Pharmacol. 2012; 69: 1213 â 1220.
dc.identifier.citedreferenceLissoni P, Meregalli S, Nosetto L, et al. Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology. 1996; 53: 43 â 46.
dc.identifier.citedreferenceCerea G, Vaghi M, Ardizzoia A, et al. Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly lowâ dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5â fluorouracilâ containing combinations. Anticancer Res. 2003; 23: 1951 â 1954.
dc.identifier.citedreferenceLissoni P, Paolorossi F, Ardizzoia A, et al. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a firstâ line treatment of advanced nonâ small cell lung cancer patients in a poor clinical state. J Pineal Res. 1997; 23: 15 â 19.
dc.identifier.citedreferenceSaini N, Gordenin DA. Somatic mutation load and spectra: a record of DNA damage and repair in healthy human cells. Environ Mol Mutagen. 2018; 59: 672 â 686.
dc.identifier.citedreferenceCastle JC, Kreiter S, Diekmann J, et al. Exploiting the mutanome for tumor vaccination. Cancer Res. 2012; 72: 1081 â 1091.
dc.identifier.citedreferenceMajidinia M, Sadeghpour A, Mehrzadi S, et al. Melatonin: a pleiotropic molecule that modulates DNA damage response and repair pathways. J Pineal Res. 2017; 63: e12416.
dc.identifier.citedreferenceMaestroni GJ. The immunoneuroendocrine role of melatonin. J Pineal Res. 1993; 14: 1 â 10.
dc.identifier.citedreferenceMaestroni GJ. Therapeutic potential of melatonin in immunodeficiency states, viral diseases, and cancer. Adv Exp Med Biol. 1999; 467: 217 â 226.
dc.identifier.citedreferenceEspino J, Rodriguez AB, Pariente JA. The inhibition of TNFâ alphaâ induced leucocyte apoptosis by melatonin involves membrane receptor MT1/MT2 interaction. J Pineal Res. 2013; 54: 442 â 452.
dc.identifier.citedreferenceVriend J, Reiter RJ. Melatonin feedback on clock genes: a theory involving the proteasome. J Pineal Res. 2015; 58: 1 â 11.
dc.identifier.citedreferenceSimonneaux V, Ribelayga C. Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacol Rev. 2003; 55: 325 â 395.
dc.identifier.citedreferenceBotros HG, Legrand P, Pagan C, et al. Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. J Pineal Res. 2013; 54: 46 â 57.
dc.identifier.citedreferenceMa X, Idle JR, Krausz KW, et al. Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos. 2005; 33: 489 â 494.
dc.identifier.citedreferenceSu SC, Hsieh MJ, Yang WE, et al. Cancer metastasis: mechanisms of inhibition by melatonin. J Pineal Res. 2017; 62: e12370.
dc.identifier.citedreferenceMaschioâ Signorini LB, Gelaleti GB, Moschetta MG, et al. Melatonin regulates angiogenic and inflammatory proteins in MDAâ MBâ 231 cell line and in coâ culture with cancerâ associated fibroblasts. Anticancer Agents Med Chem. 2016; 16: 1474 â 1484.
dc.identifier.citedreferenceJardimâ Perassi BV, Lourenco MR, Doho GM, et al. Melatonin regulates angiogenic factors under hypoxia in breast cancer cell lines. Anticancer Agents Med Chem. 2016; 16: 347 â 358.
dc.identifier.citedreferenceXu CS, Wang ZF, Huang XD, et al. Involvement of ROSâ alpha v beta 3 integrinâ FAK/Pyk2 in the inhibitory effect of melatonin on U251 glioma cell migration and invasion under hypoxia. J Transl Med. 2015; 13: 95.
dc.identifier.citedreferenceAlvarezâ Garcia V, Gonzalez A, Alonsoâ Gonzalez C, et al. Melatonin interferes in the desmoplastic reaction in breast cancer by regulating cytokine production. J Pineal Res. 2012; 52: 282 â 290.
dc.identifier.citedreferenceMarx V. Nextâ generation sequencing: the genome jigsaw. Nature. 2013; 501: 263 â 268.
dc.identifier.citedreferenceThe Cancer Genome Atlas Research Network, Weinstein JN, Collisson EA, et al. The Cancer Genome Atlas Panâ Cancer analysis project. Nat Genet. 2013; 45: 1113 â 1120.
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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