Current advances on single or multi-omics analysis of esophageal cancer

Kaidirina Kasimu, Wenwen Cui, Yihan Wang, Xin Li, Hongbo Wang, Xiaotong Yu, Fu Ren

Abstract


Esophageal cancer is associated with high mortality rates and is one of the cancers with the worst prognosis. Its incidence has significant regional specificity, particularly in China where it is much higher than in other countries. Moreover, effective diagnostic markers, therapeutic targets, and molecular subtyping biomarkers are currently lacking for esophageal cancer. Nevertheless, large-scale omics studies have identified dozens of robust genetic risk loci and prognosis-related loci, drawn genomic, epigenomic, and transcriptomic maps of esophageal cancer at multiple molecular levels, and described significant differences between esophageal squamous cell carcinoma and adenocarcinoma. These studies are of great significance for exploring the occurrence and development mechanism of esophageal cancer, guiding clinical treatment, and improving patient prognosis. This review, from the perspective of multi-omics, discusses the analytical strategies employed in these studies and summarizes their core findings. It emphasizes that the integration and analysis of multi-omics data is a key focus and development trend in the precise medical research of esophageal cancer, and has broad research and application prospects.

Keywords: Esophageal cancer; GWAS; Precision medicine; Biomarker   


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Chen W, Zheng R, Baade PD, Zhang S, Zeng H. et al. Cancer statistics in China, 2015: Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians (2016); 66:115–132.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA A Cancer Journal for Clinicians, (2019); 69:7–34.

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J. et al. Global cancer statistics, 2012: Global Cancer Statistics, 2012. CA: A Cancer Journal for Clinicians (2015); 65:87–108.

Li H, Mu F, Zou B, Wang L. Pulmonary sarcoidosis-like reactions induced by sintilimab in esophageal cancer: A case report. Medicine, (2023); 102: e34432.

Siewert JR, Ott K. Are Squamous and Adenocarcinomas of the Esophagus the Same Disease? Seminars in Radiation Oncology, (2007); 17:38–44.

Dai J, Shen W, Wen W, Chang J, Wang T. et al. Estimation of heritability for nine common cancers using data from genome-wide association studies in Chinese population: Estimation of heritability for nine common cancers. International Journal of Cancer, (2017); 140:329–336.

Contino G, Vaughan TL, Whiteman D, Fitzgerald RC. The Evolving Genomic Landscape of Barrett’s Esophagus and Esophageal Adenocarcinoma. Gastroenterology, (2017); 153:657-673.e1.

Ek WE, Levine DM, D’Amato M, Pedersen NL, Magnusson PKE. et al. Germline Genetic Contributions to Risk for Esophageal Adenocarcinoma, Barrett’s Esophagus, and Gastroesophageal Reflux. JNCI Journal of the National Cancer Institute, (2013); 105:1711–1718.

Gharahkhani P, Fitzgerald RC, Vaughan TL, Palles C, Gockel I. et al. Genome-wide association studies in oesophageal adenocarcinoma and Barrett’s oesophagus: a large-scale meta-analysis. The Lancet Oncology, (2016); 17:1363–1373.

Levine DM, Ek WE, Zhang R, Liu X, Onstad L. et al. A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett’s esophagus. Nature Genetics, (2013); 45:1487–1493.

Palles C, Chegwidden L, Li X, Findlay JM, Farnham G. et al. Polymorphisms Near TBX5 and GDF7 Are Associated With Increased Risk for Barrett’s Esophagus. Gastroenterology, (2015); 148:367–378.

The Esophageal Adenocarcinoma Genetics Consortium, The Wellcome Trust Case Control Consortium 2, Su Z, Gay LJ, Strange A. et al. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett’s esophagus. Nature Genetics, (2012); 44:1131–1136.

Hyland PL, Zhang H, Yang Q, Yang HH, Hu N. et al. Pathway, in silico and tissue-specific expression quantitative analyses of oesophageal squamous cell carcinoma genome-wide association studies data. Internatonal Journal of Epidemiology, (2016); 45:206–220.

Tian J, Liu C, Liu G, Zuo C, Chen H. Cumulative evidence for association between genetic polymorphisms and esophageal cancer susceptibility: A review with evidence from meta‐analysis and genome‐wide association studies. Cancer Medicine, (2019); 8:1289–1305.

Abnet CC, Freedman ND, Hu N, Wang Z, Yu K. et al. A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. Nature Genetics, (2010); 42:764–767.

Wang L-D, Zhou F-Y, Li X-M, Sun L-D, Song X. et al. Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies a susceptibility locus at PLCE1. Nature Genetics, (2010); 42:759–763.

Wu C, Hu Z, He Z, Jia W, Wang F. et al. Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Nature Genetics, (2011); 43:679–684.

Wu C, Kraft P, Zhai K, Chang J, Wang Z. et al. Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions. Nature Genetics, (2012); 44:1090–1097.

Wu C, Li D, Jia W, Hu Z, Zhou Y. et al. Genome-wide association study identifies common variants in SLC39A6 associated with length of survival in esophageal squamous-cell carcinoma. Nature Genetics, (2013); 45:632–638.

Wu C, Wang Z, Song X, Feng X-S, Abnet CC. et al. Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations. Nat Genet (2014); 46:1001–1006.

Wang K-L, Chen X-L, Lei L, Li P, Hong L-L. et al., Huang X-C, Mao W-M, Mukaisho K, Ling Z-Q. Validation study of susceptibility loci for esophageal squamous cell carcinoma identified by GWAS in a Han Chinese subgroup from Eastern China. Journal of Cancer, (2019); 10:3624–3631.

Yan C, Ji Y, Huang T, Yu F, Gao Y. et al. An esophageal adenocarcinoma susceptibility locus at 9q22 also confers risk to esophageal squamous cell carcinoma by regulating the function of BARX1. Cancer Letters, (2018); 421:103–111.

Sung H, Yang HH, Zhang H, Yang Q, Hu N. et al. Common genetic variants in epigenetic machinery genes and risk of upper gastrointestinal cancers. International Journal of Epidemiology, (2015); 44:1341–1352.

Yang N, Ying P, Tian J, Wang X, Mei S Genetic variants in m6A modification genes are associated with esophageal squamous-cell carcinoma in the Chinese population. Carcinogenesis, (2020); 41:761–768.

Hu JL, Hu XL, Lu CX, Chen XJ, Fu L Variants in the 3’-untranslated region of CUL3 is associated with risk of esophageal squamous cell carcinoma. Journal of Cancer (2018); 9:3647–3650.

Schröder J, Schüller V, May A, Gerges C, Anders M. et al. Identification of loci of functional relevance to Barrett’s esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. PLoS ONE, (2019); 14: e0227072.

Shao Y, Guo X, Zhao L, Shen Y, Niu C. et al. A Functional Variant of the miR-15 Family Is Associated with a Decreased Risk of Esophageal Squamous Cell Carcinoma. DNA and Cell Biology, (2020); 39:1583–1594.

Cui Q, Peng L, Wei L, Chang J, Tan W. et al. Genetic variant repressing ADH1A expression confers susceptibility to esophageal squamous-cell carcinoma. Cancer Letters, (2018); 421:43–50.

Peng L, Cheng S, Lin Y, Cui Q, Luo Y. et al. CCGD-ESCC: A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population. Genomics, Proteomics & Bioinformatics, (2018); 16:262–268.

Agrawal N, Jiao Y, Bettegowda C, Hutfless SM, Wang Y. et al. Comparative Genomic Analysis of Esophageal Adenocarcinoma and Squamous Cell Carcinoma. Cancer Discovery, (2012); 2:899–905.

Gao YB, Chen ZL, Li JG, Hu XD, Shi XJ, et al. Genetic landscape of esophageal squamous cell carcinoma. Nature Genetics, (2014); 46:1097–1102.

Song Y, Li L, Ou Y, Gao Z, Li E. et al. Identification of genomic alterations in oesophageal squamous cell cancer. Nature, (2014); 509:91–95.

Sawada G, Niida A, Uchi R, Hirata H, Shimamura T. et al. Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population. Gastroenterology, (2016); 150:1171–1182.

Cui Y, Chen H, Xi R, Cui H, Zhao Y. et al. Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal squamous cell carcinoma. Cell Research, (2020); 30:902–913.

Cao W, Lee H, Wu W, Zaman A, McCorkle S. et al. Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma. Nature Communication, (2020); 11:3675.

The Cancer Genome Atlas Research Network. Integrated genomic characterization of oesophageal carcinoma. Nature (2017); 541:169–175.

Zhang L, Zhou Y, Cheng C, Cui H, Cheng L. et al. Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma. The American Journal of Human Genetics, (2020); 107:375.

Yan T, Cui H, Zhou Y, Yang B, Kong P, et al. Multi-region sequencing unveils novel actionable targets and spatial heterogeneity in esophageal squamous cell carcinoma. Nature Communication, (2019); 10:1670.

Cheng C, Zhou Y, Li H, Xiong T, Li S. et al. Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma. The American Journal of Human Genetics, (2016); 98:256–274.

Chen XX, Zhong Q, Liu Y, Yan SM, Chen ZH. et al. Genomic comparison of esophageal squamous cell carcinoma and its precursor lesions by multi-region whole-exome sequencing. Nature Communication, (2017); 8:524.

Lin DC, Hao JJ, Nagata Y, Xu L, Shang L, et al. Genomic and molecular characterization of esophageal squamous cell carcinoma. Nature Genetics, (2014); 46:467–473.

Lin DC, Dinh HQ, Xie JJ, Mayakonda A, Silva TC, et al. Identification of distinct mutational patterns and new driver genes in oesophageal squamous cell carcinomas and adenocarcinomas. Gut, (2018); 67:1769–1779.

Qin H-D, Liao X-Y, Chen Y-B, Huang S-Y, Xue W-Q. et al. Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis. American Journal of Human Genetics, (2016); 98:709–727.

Martincorena I, Fowler JC, Wabik A, Lawson ARJ, Abascal F. et al. Somatic mutant clones colonize the human esophagus with age. Science, (2018); 362:911–917.

Yokoyama A, Kakiuchi N, Yoshizato T, Nannya Y, Suzuki H. et al. Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature, (2019); 565:312–317.

Chang J, Tan W, Ling Z, Xi R, Shao M. et al. Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations. Nature Communication, (2017);

:15290.

Dong J, Maj C, Tsavachidis S, Ostrom QT, Gharahkhani P. et al. Sex-Specific Genetic Associations for Barrett’s Esophagus and Esophageal Adenocarcinoma. Gastroenterology, (2020); 159:2065-2076.e1.

Deng J, Chen H, Zhou D, Zhang J, Chen Y, et al. Comparative genomic analysis of esophageal squamous cell carcinoma between Asian and Caucasian patient populations. Nature Communication, (2017); 8:1533.

Hao JJ, Lin DC, Dinh HQ, Mayakonda A, Jiang Y-Y. et al. Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma. Nature Genetics, (2016); 48:1500–1507.




DOI: http://dx.doi.org/10.62940/als.v11i2.3106

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