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. 2022 Mar 23:13:830601.
doi: 10.3389/fgene.2022.830601. eCollection 2022.

Multi-Region Genomic Landscape Analysis for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Carcinoma

Shaofeng Lin  1 , Yanping Chen  2 , Jianchao Wang  2 , Yibin Cai  1 , Xiaohui Chen  1 , Yuanmei Chen  1 , Yi Shi  3 , Gang Chen  2 , Kunshou Zhu  1
Affiliations

Multi-Region Genomic Landscape Analysis for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Carcinoma

Shaofeng Lin et al. Front Genet. .

Abstract

Objective: Esophageal cancer is an aggressive malignant tumor, with 90 percent of the patients prone to recurrence and metastasis. Although recent studies have identified some potential biomarkers, these biomarkers' clinical or pathological significance is still unclear. Therefore, it is urgent to further identify and study novel molecular changes occurring in esophageal cancer. It has positive clinical significance to identify a tumor-specific mutation in patients after surgery for an effective intervention to improve the prognosis of patients. Methods: In this study, we performed whole-exome sequencing (WES) on 33 tissue samples from six esophageal cancer patients with lymph node metastasis, compared the differences in the genomic and evolutionary maps in different tissues, and then performed pathway enrichment analysis on non-synonymous mutation genes. Finally, we sorted out the somatic mutation data of all patients to analyze the subclonality of each tumor. Results: There were significant differences in somatic mutations between the metastatic lymph nodes and primary lesions in the six patients. Clustering results of pathway enrichment analysis indicated that the metastatic lymph nodes had certain commonalities. Tumors of the cloned exploration results illustrated that five patients showed substantial heterogeneity. Conclusion: WES technology can be used to explore the differences in regional evolutionary maps, heterogeneity, and detect patients' tumor-specific mutations. In addition, an in-depth understanding of the ontogeny and phylogeny of tumor heterogeneity can help to further find new molecular changes in esophageal cancer, which can improve the prognosis of EC patients and provide a valuable reference for their diagnosis.

Keywords: esophageal carcinoma; lymph node metastases; multi-region sequencing; subclone; whole-exome sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer (LF) declared a past co-authorship with the author (GC) to the handling editor.

Figures

FIGURE 1
FIGURE 1
Overview of the main workflow.
FIGURE 2
FIGURE 2
Somatic mutations in tumor samples. (A) Histogram of non-synonymous mutation counts with mutation frequency greater than 5% in primary samples. (B) Histogram of non-synonymous mutation counts with mutation frequency greater than 5% in LN samples. (C) Mutation spectrum of LNs and primary: the column represents the sample, the row represents the site, and each cell represents the mutation count of the sample at that site.
FIGURE 3
FIGURE 3
KEGG pathway enrichment in multi-region of primary and metastatic LNs.
FIGURE 4
FIGURE 4
Subclones of primary and metastatic LNs in all samples generated by using PyClone were composed. Each panel represents a patient, the x-axis represents not a time but a sample, and the y-axis represents the mean cell prevalence of variation in all clusters in each sample. (A–F) Patients 1 to 6.
FIGURE 5
FIGURE 5
Fish diagram of each patient’s tumor clone envelogram.
See this image and copyright information in PMC

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References

    1. Alderson D., Langley R. E., Nankivell M. G., Blazeby J. M., Griffin M., Crellin A., et al. (2015). Neoadjuvant Chemotherapy for Resectable Oesophageal and Junctional Adenocarcinoma: Results from the UK Medical Research Council Randomised OEO5 Trial (ISRCTN 01852072). J. Clin. Oncol. 33 (15_Suppl. l), 4002. 10.1200/jco.2015.33.15_suppl.4002 - DOI
    1. Allum W. H., Blazeby J. M., Griffin S. M., Cunningham D., Jankowski J. A., Wong R. (2011). Guidelines for the Management of Oesophageal and Gastric Cancer. Gut 60 (11), 1449–1472. 10.1136/gut.2010.228254 - DOI - PubMed
    1. Bolton W. D., Hofstetter W. L., Francis A. M., Correa A. M., Ajani J. A., Bhutani M. S., et al. (2009). Impact of Tumor Length on Long-Term Survival of pT1 Esophageal Adenocarcinoma. J. Thorac. Cardiovasc. Surg. 138 (4), 831–836. 10.1016/j.jtcvs.2009.02.003 - DOI - PubMed
    1. Cao W., Wu W., Yan M., Tian F., Ma C., Zhang Q., et al. (2015). Multiple Region Whole-Exome Sequencing Reveals Dramatically Evolving Intratumor Genomic Heterogeneity in Esophageal Squamous Cell Carcinoma. Oncogenesis 4 (11), e175. 10.1038/oncsis.2015.34 - DOI - PMC - PubMed
    1. Chadwick G., Groene O., Taylor A., Riley S., Hardwick R. H., Crosby T., et al. (2016). Management of Barrett's High-Grade Dysplasia: Initial Results From a Population-Based National Audit. Gastrointest Endosc. 83 (4), 736–742.e1. 10.1016/j.gie.2015.08.020 - DOI - PubMed

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