Single-cell transcriptomic analysis of gingivo-buccal oral cancer reveals two dominant cellular programs.
cellular diversity
fetal cell-type signature
partial epithelial-mesenchymal transition
single-cell RNA sequencing
tumor ecosystem
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
04 Oct 2023
04 Oct 2023
Historique:
revised:
02
09
2023
received:
23
06
2023
accepted:
13
09
2023
medline:
4
10
2023
pubmed:
4
10
2023
entrez:
4
10
2023
Statut:
aheadofprint
Résumé
Oral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) is the most common cancer among men in India, and is associated with poor prognosis and frequent recurrence. Cellular heterogeneity in OSCC-GB was investigated by single-cell RNA sequencing of tumors derived from the oral cavity of 12 OSCC-GB patients, 3 of whom had concomitant presence of a precancerous lesion (oral submucous fibrosis [OSMF]). Unique malignant cell types, features, and phenotypic shifts in the stromal cell population were identified in oral tumors with associated submucous fibrosis. Expression levels of FOS, ATP1A, and DUSP1 provided robust discrimination between tumors with or without the concomitant presence of OSMF. Malignant cell populations shared between tumors with and without OSMF were enriched with the expression of partial epithelial-mesenchymal transition (pEMT) or fetal cell type signatures indicative of two dominant cellular programs in OSCC-GB-pEMT and fetal cellular reprogramming. Malignant cells exhibiting fetal cellular and pEMT programs were enriched with the expression of immune-related pathway genes known to be involved in antitumor immune response. In the tumor microenvironment, higher infiltration of immune cells than the stromal cells was observed. The T cell population was large in tumors and diverse subtypes of T cells with varying levels of infiltration were found. We also detected double-negative PLCG2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Department of Biotechnology, Ministry of Science and Technology, India BT/Med-II/NIBMG/SyMeC/2014/Vol.II
Informations de copyright
© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Références
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
de Camargo CM, Voti L, Guerra-Yi M, Chapuis F, Mazuir M, Curado MP. Oral cavity cancer in developed and in developing countries: population-based incidence. Head Neck. 2010;32(3):357-367. doi:10.1002/hed.21193
Hua X, Zhao W, Pesatori AC, et al. Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma. Nat Commun. 2020;11(1):2459. doi:10.1038/s41467-020-16295-5
Park SY, Gönen M, Kim HJ, Michor F, Polyak K. Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. J Clin Investig. 2010;120(2):636-644. doi:10.1172/JCI40724
Sottoriva A, Spiteri I, Piccirillo SGM, et al. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci U S A. 2013;110(10):4009-4014. doi:10.1073/pnas.1219747110
Tanay A, Regev A. Scaling single-cell genomics from phenomenology to mechanism. Nature. 2017;541(7637):331-338. doi:10.1038/nature21350
Puram SV, Tirosh I, Parikh AS, et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell. 2017;171(7):1611-1624.e24. doi:10.1016/j.cell.2017.10.044
Cillo AR, Kürten CHL, Tabib T, et al. Immune landscape of viral- and carcinogen-driven head and neck cancer. Immunity. 2020;52(1):183-199.e9. doi:10.1016/j.immuni.2019.11.014
Kürten CHL, Kulkarni A, Cillo AR, et al. Investigating immune and non-immune cell interactions in head and neck tumors by single-cell RNA sequencing. Nat Commun. 2021;12(1):7338. doi:10.1038/s41467-021-27619-4
Das D, Maitra A, Panda CK, et al. Genes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer. NPJ Genom Med. 2021;6(1):32. doi:10.1038/s41525-021-00195-8
Hao Y, Hao S, Andersen-Nissen E, et al. Integrated analysis of multimodal single-cell data. Cell. 2021;184(13):3573-3587.e29. doi:10.1016/j.cell.2021.04.048
Tickle TI, Georgescu C, Brown M, Haas B. inferCNV of the Trinity CTAT Project.
Qiu X, Mao Q, Tang Y, et al. Reversed graph embedding resolves complex single-cell trajectories. Nat Methods. 2017;14(10):979-982. doi:10.1038/nmeth.4402
Wang C, Gu Y, Zhang K, et al. Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types. Nat Commun. 2016;7(1):10499. doi:10.1038/ncomms10499
Hillhouse EE, Lesage S. A comprehensive review of the phenotype and function of antigen-specific immunoregulatory double negative T cells. J Autoimmun. 2013;40(1):58-65. doi:10.1016/j.jaut.2012.07.010
Fu G, Chen Y, Schuman J, Wang D, Wen R. Phospholipase Cγ2 plays a role in TCR signal transduction and T cell selection. J Immunol. 2012;189(5):2326-2332. doi:10.4049/jimmunol.1103458
Anderson G, Jenkinson EJ. Lymphostromal interactions in thymic development and function. Nat Rev Immunol. 2001;1(1):31-40. doi:10.1038/35095500
Kumar BV, Connors TJ, Farber DL. Human T cell development, localization, and function throughout life. Immunity. 2018;48(2):202-213. doi:10.1016/j.immuni.2018.01.007
Crawford A, Angelosanto JM, Kao C, et al. Molecular and transcriptional basis of CD4+ T cell dysfunction during chronic infection. Immunity. 2014;40(2):289-302. doi:10.1016/j.immuni.2014.01.005
Heger L, Balk S, Lühr JJ, et al. CLEC10A is a specific marker for human CD1c+ dendritic cells and enhances their toll-like receptor 7/8-induced cytokine secretion. Front Immunol. 2018;9:744. doi:10.3389/fimmu.2018.00744
Alqassim EY, Sharma S, Khan ANMNH, et al. RNA editing enzyme APOBEC3A promotes pro-inflammatory M1 macrophage polarization. Commun Biol. 2021;4(1):102. doi:10.1038/s42003-020-01620-x
Sun SG, Guo JJ, Qu XY, et al. The extracellular vesicular pseudogene LGMNP1 induces M2-like macrophage polarization by upregulating LGMN and serves as a novel promising predictive biomarker for ovarian endometriosis recurrence. Hum Reprod. 2022;37(3):447-465. doi:10.1093/humrep/deab266
Umbarawan Y, Enoura A, Ogura H, et al. Fabp5 is a sensitive marker for lipid-rich macrophages in the luminal side of atherosclerotic lesions. Int Heart J. 2021;62(3):666-676. doi:10.1536/ihj.20-676
Jiang Y, Zhang S, Tang L, et al. Single-cell RNA sequencing reveals TCR+ macrophages in HPV-related head and neck squamous cell carcinoma. Front Immunol. 2022;13:1030222. doi:10.3389/fimmu.2022.1030222
del Toro R, Prahst C, Mathivet T, et al. Identification and functional analysis of endothelial tip cell-enriched genes. Blood. 2010;116(19):4025-4033. doi:10.1182/blood-2010-02-270819
Annan DA, Maishi N, Soga T, et al. Carbonic anhydrase 2 (CAII) supports tumor blood endothelial cell survival under lactic acidosis in the tumor microenvironment. Cell Commun Signal. 2019;17(1):169. doi:10.1186/s12964-019-0478-4
Jha SK, Rauniyar K, Jeltsch M. Key molecules in lymphatic development, function, and identification. Ann Anat. 2018;219:25-34. doi:10.1016/j.aanat.2018.05.003
Pan Y, di Wang W, Yago T. Transcriptional regulation of podoplanin expression by Prox1 in lymphatic endothelial cells. Microvasc Res. 2014;94:96-102. doi:10.1016/j.mvr.2014.05.006
Chen DY, Sun NH, Chen X, et al. Endothelium-derived semaphorin 3G attenuates ischemic retinopathy by coordinating β-catenin-dependent vascular remodeling. J Clin Investig. 2021;131(4):e135296. doi:10.1172/JCI135296
Schupp JC, Adams TS, Cosme C, et al. Integrated single-cell atlas of endothelial cells of the human lung. Circulation. 2021;144(4):286-302. doi:10.1161/CIRCULATIONAHA.120.052318
Miners JS, Schulz I, Love S. Differing associations between Aβ accumulation, hypoperfusion, blood-brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer's disease. J Cereb Blood Flow Metab. 2018;38(1):103-115. doi:10.1177/0271678X17690761
Sakhneny L, Epshtein A, Landsman L. Pericytes contribute to the islet basement membranes to promote beta-cell gene expression. Sci Rep. 2021;11(1):2378. doi:10.1038/s41598-021-81774-8
Li H, Courtois ET, Sengupta D, et al. Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors. Nat Genet. 2017;49(5):708-718. doi:10.1038/ng.3818
India Project Team of ICGC. Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups. Nat Commun. 2013;4(1):2873. doi:10.1038/ncomms3873
Wu F, Fan J, He Y, et al. Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer. Nat Commun. 2021;12(1):2540. doi:10.1038/s41467-021-22801-0
Tirosh I, Izar B, Prakadan SM, et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science (1979). 2016;352(6282):189-196. doi:10.1126/science.aad0501
Yong KJ, Gao C, Lim JSJ, et al. Oncofetal gene SALL4 in aggressive hepatocellular carcinoma. N Engl J Med. 2013;368(24):2266-2276. doi:10.1056/nejmoa1300297
Nusse YM, Savage AK, Marangoni P, et al. Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche. Nature. 2018;559(7712):109-113. doi:10.1038/s41586-018-0257-1
Sharma A, Seow JJW, Dutertre CA, et al. Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in hepatocellular carcinoma. Cell. 2020;183(2):377-394.e21. doi:10.1016/j.cell.2020.08.040
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105-111. doi:10.1038/35102167
Sha Y, Haensel D, Gutierrez G, Du H, Dai X, Nie Q. Intermediate cell states in epithelial-to-mesenchymal transition. Phys Biol. 2019;16(2):021001. doi:10.1088/1478-3975/aaf928
Emprou C, le van Quyen P, Jégu J, et al. SNAI2 and TWIST1 in lymph node progression in early stages of NSCLC patients. Cancer Med. 2018;7(7):3278-3291. doi:10.1002/cam4.1545
Rahbari NN, Kedrin D, Incio J, et al. Anti-VEGF therapy induces ECM remodeling and mechanical barriers to therapy in colorectal cancer liver metastases. Sci Transl Med. 2016;8(360):360ra135. doi:10.1126/scitranslmed.aaf5219
Shah PP, Fong MY, Kakar SS. PTTG induces EMT through integrin αVβ3-focal adhesion kinase signaling in lung cancer cells. Oncogene. 2012;31(26):3124-3135. doi:10.1038/onc.2011.488
Deng B, Yang X, Liu J, He F, Zhu Z, Zhang C. Focal adhesion kinase mediates TGF-β1-induced renal tubular epithelial-to-mesenchymal transition in vitro. Mol Cell Biochem. 2010;340(1-2):21-29. doi:10.1007/s11010-010-0396-7
Fang L, Ly D, Wang S, et al. Targeting late-stage non-small cell lung cancer with a combination of DNT cellular therapy and PD-1 checkpoint blockade. J Exp Clin Cancer Res. 2019;38(1):123. doi:10.1186/s13046-019-1126-y
di Blasi D, Boldanova T, Mori L, Terracciano L, Heim MH, de Libero G. Unique T-cell populations define immune-inflamed hepatocellular carcinoma. Cell Mol Gastroenterol Hepatol. 2020;9(2):195-218. doi:10.1016/j.jcmgh.2019.08.004
Hall M, Liu H, Malafa M, et al. Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors. J Immunother Cancer. 2016;4(1):61. doi:10.1186/s40425-016-0164-7
Li Y, Dong K, Fan X, et al. DNT cell-based immunotherapy: progress and applications. J Cancer. 2020;11(13):3717-3724. doi:10.7150/jca.39717
Lu Y, Hu P, Zhou H, et al. Double-negative T cells inhibit proliferation and invasion of human pancreatic cancer cells in co-culture. Anticancer Res. 2019;39(11):5911-5918. doi:10.21873/anticanres.13795
Jin S, Li R, Chen MY, et al. Single-cell transcriptomic analysis defines the interplay between tumor cells, viral infection, and the microenvironment in nasopharyngeal carcinoma. Cell Res. 2020;30(11):950-965. doi:10.1038/s41422-020-00402-8
Peng J, Sun BF, Chen CY, et al. Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma. Cell Res. 2019;29(9):725-738. doi:10.1038/s41422-019-0195-y
Angadi PV, Kale AD, Hallikerimath S. Evaluation of myofibroblasts in oral submucous fibrosis: correlation with disease severity. J Oral Pathol Med. 2011;40(3):208-213. doi:10.1111/j.1600-0714.2010.00995.x