Abstract
The occurrence and development of esophageal cancer (EC) is a multi-stage process involving from inflammation to invasive cancer. However, this process is very complex, and so far there are few relevant studies to reveal this process. Early diagnosis and treatment of EC is the focus of the early diagnosis and treatment of malignant tumors project in China. How to screen EC in a lower cost and more efficient way deserves to be explored. Here, we reviewed the recent advances in the mechanisms of the occurrence and development, and early diagnosis and treatment of EC.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
1 Introduction
In 2020, the number of esophageal cancer (EC) patients increased by 600,000, ranking 8th among all cancers, while the number of deaths increased by 540,000, ranking 6th among all cancers; In China, the incidence of EC increased by 320,000 in 2020, ranking the 6th, while the death rate increased by 300,000, ranking the 4th [1]. Recently, the nationwide statistics for cancer incidence and mortality in 2016 reported by National Cancer Center (NCC) of China revealed that the incidence of EC ranks 5th in male and 8th in female, and the mortality ranks 4th in male and 6th in female [2]. Thus, EC is still a major malignant tumor affecting the health of Chinese residents.
It included two main pathologic types, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). ESCC is the most common subtype, accounts for 90% of EC cases worldwide, with the highest incidence in China, Central Asia, East and South Africa, while EAC mainly occurs in South America and Europe [3]. In China, EC accounts for 70% of the world’s EC cases [4].
It still remains unknown that how EC occurs. Current studies have shown that EC is a multi-stage process that gradually develops from repeated inflammatory stimulation to precancerous lesions and then to invasive cancer. This process is very complex and involves changes in esophageal epithelial and non-epithelial cells cytogenetics in the microenvironment, and its molecular mechanisms are still being explored [5]. Some studies have shown that high frequency mutations in some driver genes are associated with the development of EC, such as p53, p16, PTEN, RB1, ZNF750 and so on [6,7,8,9,10,11,12,13].
Early esophageal cancer is defined as the lesion only involving the mucosa without suspected lymph node metastasis [14]. About 20% patients are diagnosed with early EC, and the 5-year survival rate is about 85% after lesion resection [15, 16]. The commonly used diagnostic methods, such as Lugol's iodine staining guided biopsy under white light endoscopy (WLE) or narrow-band imaging (NBI), can well diagnose esophageal precancerous lesions and early EC. However, due to the fact that patients with esophageal precancerous lesions and early EC are mostly asymptomatic, endoscopic screening is costly and painful, so endoscopic screening is not suitable for large-scale screening, which lead to a low rate of early diagnosis, resulting in a high incidence and mortality. Due to the high cost of treatment, the large surgical trauma and large amount of complications, the quality of life of patients with middle and advanced stage of EC is poor. However, endoscopic treatments for early EC such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) not only have less trauma, long survival time, but also preserve esophageal structure and function, which maintain a high quality of life. Therefore, the early diagnosis and treatment of EC is crucial.
Traditionally, esophageal precancerous lesion was defined as atypical hyperplasia, and it was classified as mild, moderate, and severe. In recent years, WHO classification of esophageal tumors defined esophageal precancerous lesion as intraepithelial neoplasia/dysplasia, and low grade and high grade were classified based on the depth of invasion. Low grade intraepithelial neoplasia/dysplasia invades the lower 1/2 of epithelium, while high grade intraepithelial neoplasia/dysplasia invades the upper 1/2 of epithelium. The tumor who invades the whole epithelium is called carcinoma in situ (CIS) [17].
This article reviews the recent advances in the pathogenesis, biomarkers, and diagnostic methods of esophageal precancerous lesions and early EC.
2 Advances in the mechanisms of esophageal precancerous lesions and early EC
The progression of EC from precancerous lesions to invasive carcinoma is very complex. With the development of sequencing techniques, researchers have gradually revealed some key genes and pathways affecting the occurrence and development of EC through sequencing. Academician Qimin Zhan et al. found significant mutations in 8 genes through genomic analysis of 158 cases of ESCC (TP53, RB1, CDKN2A, PIK3CA, NOTCH1, NFE2L2, ADAM29, FAM135B), among which FAM135B, which was never reported to be related to ESCC, was proved to enhance the malignancy of tumor cells. At the same time, mutations in ESCC were mainly involved in Wnt, cell cycle, Notch, RTK-Ras and AKT pathways. PSMD2, RARRES1, SRC, GSK3B and SGK3 could be potential novel therapeutic targets [6]. By sequencing exons of 113 EC patients, Academician Jie He et al. found that genes related to cell cycle and apoptosis pathway were mutated in 99% of the samples, mainly including TP53, CCND1, CDKN2A, NFE2L2 and RB1. The frequency of histone modification related gene mutations was also high, including KMT2D, KMT2C, KDM6A, EP300 and CREBBP, among which EP300 mutation was associated with poor prognosis. In addition, mutations in FAT1, FAT2, FAT3 or FAT4 or AJUBA and NOTCH1, NOTCH2 or NOTCH3 or FBXW7 were found to cause dysregulation of Hippo and Notch pathways, respectively [18]. Although some studies have found some tumor biomarkers for ESCC, new biomarkers for diagnosis are still insufficient [9, 19, 20]. Recent genomic studies, including The Cancer Genome Atlas (TCGA) project, have identified many genomic mutations in ESCC by using whole-exome or whole-genome sequencing of clinical tissue samples [21]. The team of Academician Dongxin Lin found two functional single-nucleotide polymorphisms (SNPs), rs671 in ALDH2 on 4q23 and rs1229984 in ADH1B on 12q24, that were significantly associated with the risk of ESCC in a manner of interactions with alcohol drinking and tobacco smoking status [22, 23]. They further sequenced the whole genome and identified six ESCC mutational signature (E1-E6) among which E4 was significantly associated with smoking and drinking status. In addition, the frequency of Signature E4 in drinkers with ALDH2 risk genotype (rs671-AG/-AA) was significantly higher than that in drinkers without such risk genotype. It was also significantly higher than non-drinkers with this risk genotype or non-drinkers with rs671-GG genotype. The analysis results of AGH1B were similar to those of ALDH2 [21]. Although these studies revealed the pathogenesis of EC from some aspects, they were only limited to the invasive stage, rather than the process from precancerous lesions to invasive cancer, so they could not fully reveal the mechanism of the occurrence and development of EC.
Previous studies have shown that chronic inflammation of the cellular microenvironment is a strong risk factor for digestive system tumors [24, 25]. Reactive oxygen and nitrogen species (RONS) induced by chronic inflammation can damage important cellular components (such as DNA, proteins and lipids), thereby leading to malignant cell transformation [26]. Lin et al. showed that the malignant severity of esophageal mucosa histology increased with the degree of inflammation [27]. They conducted whole exon and whole genome sequencing on 227 tissues including normal epithelial tissues, simple hyperplasia tissues, intraepithelial neoplasia tissues and EC tissues, revealing the change process from normal mucosal tissues to intraepithelial neoplasia and then to invasive carcinoma [27]. Their research showed that the damage status and degree of inflammation of DNA are positively correlated with the degree of atypia of the mucosal tissue. The positive rate of phosphorylated H2AX (γH2AX) in the intraepithelial neoplasia tissue is significantly higher than that in the normal tissue and simple hyperplasia tissue. The positive rate of γH2AX was different in non-inflammatory tissues and inflammatory tissues, and the expression of γH2AX increased with the increase of the degree of inflammation and the degree of cellular atypia. In addition, they found that the increase in genomic ploidy began at the stage of intraepithelial neoplasia, for example, polyploidy was present in 68% of intraepithelial neoplasia and 55.6% of squamous cell carcinoma samples, but not in simple hyperplasia samples. Finally, they also identified several mutated genes that are common in both intraepithelial neoplasia and squamous cell carcinoma, such as CDKN2A, ASCL3, FEV, CCND1, NFE2L2, and SOX2. Although there was no difference in the size of the copy number variation (CNA) between intraepithelial neoplasia and squamous cell carcinoma, squamous cell carcinoma showed a wide increase in the CNA status. Although there are many common genetic changes in squamous cell carcinoma and intraepithelial neoplasia, there are still unique mutations between them, indicating genetic heterogeneity [28].
Only the study of genomics is far from enough, the study of proteomics is a supplement to the study of genomics. Zhang et al. performed proteomic analysis of high-grade intraepithelial neoplasia and normal mucosal tissues and compared the difference in protein expression between the two groups [29]. 4006 proteins were identified, and compared with normal mucosa tissues, 236 proteins were differential expressed, among which 138 were up-regulated and 98 were down-regulated. What’s more, 18 proteins were proved to be differential expressed between ESCC and normal tissues in previous studies. Functional enrichment analysis showed that these differentially expressed proteins were enriched in multiple functional and signaling pathways, such as regulation of actin cytoskeleton, PPAR signaling pathway, ubiquitin-mediated proteolysis, etc.
Although these studies have revealed the important role of genomic alterations in ESCC, it is not clear how normal epithelial cells progress from precancerous lesions to invasive cancers by mutation because most of these studies are based on cross-sectional designs rather than sequential progression or involve fewer stages of disease. In addition, a few somatic mutations may not be sufficient to initiate the occurrence and development of EC, as such mutations also occur in pathologically normal human esophageal tissue [30].
The complex background of tumor microenvironment (TME) also plays an important role in the occurrence and development of tumors. Therefore, it is of great significance to elucidate the dynamic transcriptome changes of cells in TME during tumorigenesis to reveal the development of ESCC. Single cell transcriptome analysis can analyze complex cell composition and decipher cell state transitions in tissue samples [31]. However, it is difficult to analyze continuously progressing tumors because it is almost impossible to obtain these lesions from patients, so the solution has to be found in animal models. The chemical carcinogen 4-nitroquinoline 1-oxide (4NQO) can induce the development of ESCC in mice in a manner similar to the tumorigenic process of human ESCC [32, 33].
Therefore, the study on the development process of ESCC by constructing a mouse model is helpful to understand the development process of human ESCC. The analysis of each stage of the progression of ESCC in model mice by single cell sequencing can show the status of various cells in the esophageal epithelium at different stages of development, thus describing the panoramic picture of the progression of esophageal squamous cell carcinoma [5]. Studies have shown that during the development of ESCC, epithelial cells exhibited six different status (EpiC 1–6), which were respectively related to division and proliferation, detoxification, extracellular carcinogen stimulating response and pro-inflammatory response, keratinization, epithelial-mesenchymal transformation and angiogenesis, and control of tumor invasion and metastasis. EpiC 1–3 existed in different stages, but in different proportions, indicating that these three types of cells were basic components of esophageal epithelium, while EpiC 4 and 5 existed in inflammatory and proliferative stages, and EpiC 6 existed only in invasive tumors. In addition, these cells showed two pathways of change, both starting from EpiC 1, some cells transformed from proliferative EpiC 1 to normal differentiated EpiC 4, and some cells developed from EpiC 2 to EpiC 5, and finally to malignant EpiC 6. These cell subtypes well demonstrate the dynamic transformation of esophageal epithelial cells during tumor development.
Previous research on human esophageal genome mutations showed that although the exons mutation burden in normal human esophageal epithelial increased with age, but no cancer related lesions occurred, suggesting that transcriptome change caused by carcinogens and immunosuppressive factors might play an important role in ESCC [5]. Generally speaking, the occurrence of ESCC is caused by the combined effects of external carcinogenic stimulation, inflammatory response, gene mutation and immunosuppression.
3 Advances in early diagnosis of EC
At present, early detection, diagnosis and treatment are the best strategies to improve the prognosis of EC. If early EC is detected and treated with endoscopy or surgery, the 5-year overall survival rate can be greatly improved to more than 90% [34, 35]. However, for the screening of EC and precancerous lesions, endoscopic screening is not suitable for large-scale screening due to its high price and low efficiency. At present, it is mainly applied to the screening of EC in high-incidence areas in China. Therefore, to find effective non-invasive biomarkers for screening, reduce the cost of screening, improve the efficiency and accuracy of early diagnosis of EC will help to reduce the mortality [36].
4 Advances in biomarkers for screening
In recent years, some biomarkers for the diagnosis of EC have been developed based on esophageal cytology samples, blood samples, respiratory samples, oral microbiome, etc. [36, 37], for example, blood antibodies such as p53 antibodies, circulating tumor cells, circulating miRNAs and lncRNAs [38,39,40,41]. In addition, there are diagnostic methods that combine biopsies with biomarkers, such as DNA methylation markers, mutated genes and SNPs [11, 42].
5 Advances in endoscopic screening
At present, endoscopic screening is still the main clinical screening and early diagnosis method. The main purpose of endoscopic screening is to detect asymptomatic precancerous and early cancerous lesions and remove them, so it is very dependent on the accuracy of diagnosis. In a multicenter cohort study, EC missed in endoscopic diagnosis accounted for 6.4% of all cases [43]. Thus, improving the accuracy is the focus of the diagnosis and treatment of EC. Narrow-band imaging (NBI) can detect more areas of dysplasia while reducing the number of biopsies required [44].
In order to more intuitively and accurately evaluate the staging and histopathological types, and realize targeted biopsy and even pathological visualization, new endoscopic imaging techniques are emerging constantly. Image-enhanced endoscopy (IEE) improves the detection rate of precancerous lesions and early cancer on the basis of white light endoscopy, and avoids unnecessary biopsies [45]. Lugol chromoendoscopy (LC) can show precancerous lesions not seen under WLE and enable more accurate biopsy by showing precise boundaries [46]. I-scan technology is also a digital comparison method that can enhance the tiny mucosal structure and subtle color changes. Compared with random biopsies, i-scan guided biopsies have a higher diagnostic rate (66%) with an accuracy rate of 96% and need fewer biopsies [47, 48].
Artificial intelligence (AI), especially deep learning, is widely used in the medical field. After learning how endoscopy experts diagnose and interpret images, AI can complete the work better and more efficiently. In addition, AI is not significantly different from clinical experts in sensitivity, specificity and accuracy, and even better than some junior or intermediate physicians [49]. In the future, AI will play an increasingly important role in the field of medicine.
6 Advances in endoscopic treatment for early EC
Endoscopic eradication therapy (EET) is currently the basic treatment method for precancerous lesions of the esophagus and early EC restricted to the mucosa and submucosa without regional lymph node metastasis. It mainly includes endoscopic mucosal resection (EMR) and endoscopic submucosal resection (ESD). EET can achieve a 5-year survival rate of 95% to 100% [50]. Radiofrequency ablation (RFA) is usually used for ablation of flat or non-visible lesions, as well as those that remain after endoscopic ablation [51]. Bleeding, perforation and esophageal stenosis are common complications after endoscopic therapy. Careful coagulation of exposed vessels at the resection site can reduce the risk of delayed bleeding; Clip closure, stenting and endoscopic suture are effective methods for the treatment of intraoperative perforation [52]. Common treatments for stricture are self-help inflatable balloon, prophylactic placement of fully covered self-expandable metal stents, biodegradable stents, oral steroid administration, and local steroid injection or topical steroid gel application [49] (Fig. 1).
7 Advances in other treatments for early EC
Though endoscopic treatment is the basis for precancerous lesions of the esophagus and early EC, surgery and chemoradiotherapy are also needed. According to Esophageal cancer practice guidelines 2022 edited by the Japan Esophageal Society (JES), when it is diagnosed as having pT1a-muscularis mucosae (MM), patients with non-circumferential lesions that are recommend receiving endoscopic treatment, while patients with whole-circumferential lesions are recommend receiving surgery (if can tolerate) or chemoradiotherapy. As for patients diagnosed with submucosal (SM) after endoscopic treatment, additional treatment such as surgery or chemoradiotherapy should also be considered [53, 54]. What’s more, patients with lesion which length is > 5 cm are suggested to receive surgery. When patients are unable or unwilling to receive surgery, chemotherapy, radiotherapy or chemoradiotherapy is recommended (Fig. 1) [54].
8 Conclusion
In order to improve the therapeutic effect of patients with EC and improve the quality of life of patients, the screening and early diagnosis and treatment of high-risk groups of EC are very important, which should be one of the key points in the prevention and treatment of malignant tumors. Although the research on the pathogenesis of EC is gradually deepening, the evidence found from the genome-transcriptome-proteome is still insufficient, and no effective biological tumor markers have been found that can be used for the primary screening of large-scale population. Therefore, we still need to continue to study and explore the mechanism of occurrence and development of EC, the discovery and utilization of screening biomarkers, and early diagnosis and treatment.
Availability of data and materials
Not applicable.
Abbreviations
- EC:
-
Esophageal cancer
- NCC:
-
National Cancer Center
- ESCC:
-
Esophageal squamous cell carcinoma
- EAC:
-
Esophageal adenocarcinoma
- WLE:
-
White light endoscopy
- EMR:
-
Endoscopic mucosal resection
- ESD:
-
Endoscopic submucosal dissection
- CIS:
-
Carcinoma in situ
- TCGA:
-
The Cancer Genome Atlas
- SNPs:
-
Single-nucleotide polymorphisms
- γH2AX:
-
Phosphorylated H2AX
- CAN:
-
Copy number variation
- TME:
-
Tumor microenvironment
- 4NQO:
-
4-Nitroquinoline 1-oxide
- NBI:
-
Narrow-band imaging
- IEE:
-
Image-enhanced endoscopy
- LC:
-
Lugol chromoendoscopy
- AI:
-
Artificial intelligence
- EET:
-
Endoscopic eradication therapy
- RFA:
-
Radiofrequency ablation
- JES:
-
Japan Esophageal Society
- MM:
-
Muscularis mucosae
- SM:
-
Submucosal
References
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):209–49. https://doi.org/10.3322/caac.21660.
Zheng R, Zhang S, Zeng H, et al. Cancer incidence and mortality in China, 2016. J Natl Cancer Cent. 2022. https://doi.org/10.1016/j.jncc.2022.02.002.
Short MW, Burgers KG, Fry VT. Esophageal Cancer. Am Fam Physician. 2017;95(1):22–8.
Pennathur A, Gibson MK, Jobe BA, et al. Oesophageal carcinoma. Lancet. 2013;381(9864):400–12. https://doi.org/10.1016/S0140-6736(12)60643-6.
Yao J, Cui Q, Fan W, et al. Single-cell transcriptomic analysis in a mouse model deciphers cell transition states in the multistep development of esophageal cancer. Nat Commun. 2020;11(1):3715. https://doi.org/10.1038/s41467-020-17492-y.
Song Y, Li L, Ou Y, et al. Identification of genomic alterations in oesophageal squamous cell cancer. Nature. 2014;509(7498):91–5. https://doi.org/10.1038/nature13176.
Lin DC, Hao JJ, Nagata Y, et al. Genomic and molecular characterization of esophageal squamous cell carcinoma. Nat Genet. 2014;46(5):467–73. https://doi.org/10.1038/ng.2935.
CANCER GENOME ATLAS RESEARCH N, ANALYSIS WORKING GROUP: ASAN U, AGENCY B C C, et al. Integrated genomic characterization of oesophageal carcinoma. Nature, 2017, 541(7636): 169–75. https://doi.org/10.1038/nature20805.
Zhang L, Zhou Y, Cheng C, et al. Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma. Am J Hum Genet. 2015;96(4):597–611. https://doi.org/10.1016/j.ajhg.2015.02.017.
Cui Y, Chen H, Xi R, et al. Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal squamous cell carcinoma. Cell Res. 2020;30(10):902–13. https://doi.org/10.1038/s41422-020-0333-6.
Lin DC, Wang MR, Koeffler HP. Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and Implications for Patients. Gastroenterology. 2018;154(2):374–89. https://doi.org/10.1053/j.gastro.2017.06.066.
Jiang JH, Pi J, Jin H, et al. Oridonin-induced mitochondria-dependent apoptosis in esophageal cancer cells by inhibiting PI3K/AKT/mTOR and Ras/Raf pathways. J Cell Biochem. 2019;120(3):3736–46. https://doi.org/10.1002/jcb.27654.
Li W, Zhang L, Guo B, et al. Exosomal FMR1-AS1 facilitates maintaining cancer stem-like cell dynamic equilibrium via TLR7/NFkappaB/c-Myc signaling in female esophageal carcinoma. Mol Cancer. 2019;18(1):22. https://doi.org/10.1186/s12943-019-0949-7.
Japanese Classification of Esophageal Cancer. 11th Edition: part I. Esophagus. 2017;14(1):1–36. https://doi.org/10.1007/s10388-016-0551-7.
Wang GQ, Jiao GG, Chang FB, et al. Long-term results of operation for 420 patients with early squamous cell esophageal carcinoma discovered by screening. Ann Thorac Surg. 2004;77(5):1740–4. https://doi.org/10.1016/j.athoracsur.2003.10.098.
Zeng H, Zheng R, Zhang S, et al. Esophageal cancer statistics in China, 2011: Estimates based on 177 cancer registries. Thorac Cancer. 2016;7(2):232–7. https://doi.org/10.1111/1759-7714.12322.
Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76(2):182–8. https://doi.org/10.1111/his.13975.
Gao YB, Chen ZL, Li JG, et al. Genetic landscape of esophageal squamous cell carcinoma. Nat Genet. 2014;46(10):1097–102. https://doi.org/10.1038/ng.3076.
Pawar H, Kashyap MK, Sahasrabuddhe NA, et al. Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery. Cancer Biol Ther. 2011;12(6):510–22. https://doi.org/10.4161/cbt.12.6.16833.
Tong YS, Wang XW, Zhou XL, et al. Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma. Mol Cancer. 2015;14:3. https://doi.org/10.1186/1476-4598-14-3.
Chang J, Tan W, Ling Z, et al. Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations. Nat Commun. 2017;8:15290. https://doi.org/10.1038/ncomms15290.
Wu C, Hu Z, He Z, et al. Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Nat Genet. 2011;43(7):679–84. https://doi.org/10.1038/ng.849.
Wu C, Kraft P, Zhai K, et al. Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions. Nat Genet. 2012;44(10):1090–7. https://doi.org/10.1038/ng.2411.
SHIMIZU T, MARUSAWA H, MATSUMOTO Y, et al. Accumulation of somatic mutations in TP53 in gastric epithelium with Helicobacter pylori infection. Gastroenterology, 2014, 147(2): 407–17 e3. https://doi.org/10.1053/j.gastro.2014.04.036.
Chiba T, Marusawa H, Ushijima T. Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation. Gastroenterology. 2012;143(3):550–63. https://doi.org/10.1053/j.gastro.2012.07.009.
Kundu JK, Surh YJ. Inflammation: gearing the journey to cancer. Mutat Res. 2008;659(1–2):15–30. https://doi.org/10.1016/j.mrrev.2008.03.002.
Liu X, Zhang M, Ying S, et al. Genetic Alterations in Esophageal Tissues From Squamous Dysplasia to Carcinoma. Gastroenterology. 2017;153(1):166–77. https://doi.org/10.1053/j.gastro.2017.03.033.
Liu M, Zhang F, Liu S, et al. Loss of heterozygosity analysis of microsatellites on multiple chromosome regions in dysplasia and squamous cell carcinoma of the esophagus. Exp Ther Med. 2011;2(5):997–1001. https://doi.org/10.3892/etm.2011.297.
ZHANG J, ZHI C, ZHEN F, et al. iTRAQ-Based Quantitative Proteomic Analyses of High Grade Esophageal Squamous Intraepithelial Neoplasia. Proteomics Clin Appl, 2017, 11(11–12). https://doi.org/10.1002/prca.201600167.
Martincorena I, Fowler JC, Wabik A, et al. Somatic mutant clones colonize the human esophagus with age. Science. 2018;362(6417):911–7. https://doi.org/10.1126/science.aau3879.
Navin N, Kendall J, Troge J, et al. Tumour evolution inferred by single-cell sequencing. Nature. 2011;472(7341):90–4. https://doi.org/10.1038/nature09807.
Tang XH, Knudsen B, Bemis D, et al. Oral cavity and esophageal carcinogenesis modeled in carcinogen-treated mice. Clin Cancer Res. 2004;10(1 Pt 1):301–13. https://doi.org/10.1158/1078-0432.ccr-0999-3.
Chu J, Niu X, Chang J, et al. Metabolic remodeling by TIGAR overexpression is a therapeutic target in esophageal squamous-cell carcinoma. Theranostics. 2020;10(8):3488–502. https://doi.org/10.7150/thno.41427.
Lopes AB, Fagundes RB. Esophageal squamous cell carcinoma - precursor lesions and early diagnosis. World J Gastrointest Endosc. 2012;4(1):9–16. https://doi.org/10.4253/wjge.v4.i1.9.
Sun F, Yuan P, Chen T, et al. Efficacy and complication of endoscopic submucosal dissection for superficial esophageal carcinoma: a systematic review and meta-analysis. J Cardiothorac Surg. 2014;9:78. https://doi.org/10.1186/1749-8090-9-78.
Codipilly DC, Qin Y, Dawsey SM, et al. Screening for esophageal squamous cell carcinoma: recent advances. Gastrointest Endosc. 2018;88(3):413–26. https://doi.org/10.1016/j.gie.2018.04.2352.
Chen Y, Chen X, Yu H, et al. Oral Microbiota as promising diagnostic biomarkers for gastrointestinal cancer: a systematic review. Onco Targets Ther. 2019;12:11131–44. https://doi.org/10.2147/OTT.S230262.
Xu YW, Peng YH, Xu LY, et al. Autoantibodies: Potential clinical applications in early detection of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma. World J Gastroenterol. 2019;25(34):5049–68. https://doi.org/10.3748/wjg.v25.i34.5049.
Zhang Y, Li J, Wang L, et al. Clinical significance of detecting circulating tumor cells in patients with esophageal squamous cell carcinoma by EpCAMindependent enrichment and immunostainingfluorescence in situ hybridization. Mol Med Rep. 2019;20(2):1551–60. https://doi.org/10.3892/mmr.2019.10420.
SUDO K, KATO K, MATSUZAKI J, et al. Development and Validation of an Esophageal Squamous Cell Carcinoma Detection Model by Large-Scale MicroRNA Profiling. JAMA Netw Open, 2019, 2(5): e194573. https://doi.org/10.1001/jamanetworkopen.2019.4573.
Liu H, Zhang Q, Lou Q, et al. Differential Analysis of lncRNA, miRNA and mRNA Expression Profiles and the Prognostic Value of lncRNA in Esophageal Cancer. Pathol Oncol Res. 2020;26(2):1029–39. https://doi.org/10.1007/s12253-019-00655-8.
LI D, ZHANG L, LIU Y, et al. Specific DNA methylation markers in the diagnosis and prognosis of esophageal cancer. Aging (Albany NY), 2019, 11(23): 11640–58. https://doi.org/10.18632/aging.102569.
RODRIGUEZ DE SANTIAGO E, HERNANZ N, MARCOS-PRIETO H M, et al. Rate of missed oesophageal cancer at routine endoscopy and survival outcomes: A multicentric cohort study. United European Gastroenterol J, 2019, 7(2): 189–98. https://doi.org/10.1177/2050640618811477.
Ishihara R, Goda K, Oyama T. Endoscopic diagnosis and treatment of esophageal adenocarcinoma: introduction of Japan Esophageal Society classification of Barrett’s esophagus. J Gastroenterol. 2019;54(1):1–9. https://doi.org/10.1007/s00535-018-1491-x.
Chiu PWY, Uedo N, Singh R, et al. An Asian consensus on standards of diagnostic upper endoscopy for neoplasia. Gut. 2019;68(2):186–97. https://doi.org/10.1136/gutjnl-2018-317111.
Hashimoto CL, Iriya K, Baba ER, et al. Lugol’s dye spray chromoendoscopy establishes early diagnosis of esophageal cancer in patients with primary head and neck cancer. Am J Gastroenterol. 2005;100(2):275–82. https://doi.org/10.1111/j.1572-0241.2005.30189.x.
Hoffman A, Korczynski O, Tresch A, et al. Acetic acid compared with i-scan imaging for detecting Barrett’s esophagus: a randomized, comparative trial. Gastrointest Endosc. 2014;79(1):46–54. https://doi.org/10.1016/j.gie.2013.07.013.
Kodashima S, Fujishiro M. Novel image-enhanced endoscopy with i-scan technology. World J Gastroenterol. 2010;16(9):1043–9. https://doi.org/10.3748/wjg.v16.i9.1043.
Yang H, Hu B. Recent advances in early esophageal cancer: diagnosis and treatment based on endoscopy. Postgrad Med. 2021;133(6):665–73. https://doi.org/10.1080/00325481.2021.1934495.
NGAMRUENGPHONG S, WOLFSEN H C, WALLACE M B. Survival of patients with superficial esophageal adenocarcinoma after endoscopic treatment vs surgery. Clin Gastroenterol Hepatol, 2013, 11(11): 1424–9 e2; quiz e81. https://doi.org/10.1016/j.cgh.2013.05.025.
Fitzgerald RC, di Pietro M, Ragunath K, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut. 2014;63(1):7–42. https://doi.org/10.1136/gutjnl-2013-305372.
DRAGANOV P V, WANG A Y, OTHMAN M O, et al. AGA Institute Clinical Practice Update: Endoscopic Submucosal Dissection in the United States. Clin Gastroenterol Hepatol, 2019, 17(1): 16–25 e1. https://doi.org/10.1016/j.cgh.2018.07.041.
Minashi K, Nihei K, Mizusawa J, et al. Efficacy of Endoscopic Resection and Selective Chemoradiotherapy for Stage I Esophageal Squamous Cell Carcinoma. Gastroenterology. 2019;157(2):382–90.e3. https://doi.org/10.1053/j.gastro.2019.04.017.
Kitagawa Y, Ishihara R, Ishikawa H, et al. Esophageal cancer practice guidelines 2022 edited by the Japan esophageal society: part 1. Esophagus. 2023;20(3):343–72. https://doi.org/10.1007/s10388-023-00993-2.
Acknowledgements
Not applicable.
Funding
None.
Author information
Authors and Affiliations
Contributions
DJ and YM searched the literatures and wrote this manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Jin, D., Mao, Y. Recent advances in the mechanisms of development and the early diagnosis and treatment of esophageal cancer. Holist Integ Oncol 2, 33 (2023). https://doi.org/10.1007/s44178-023-00056-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s44178-023-00056-7