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BioMed Research International Volume 2017 ,2017-03-14
Racial Differences in Esophageal Squamous Cell Carcinoma: Incidence and Molecular Features
Research Article
Shirui Chen 1 Kai Zhou 2 Liguang Yang 3 Guohui Ding 3 Hong Li 3
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DOI:10.1155/2017/1204082
Received 2016-11-16, accepted for publication 2017-03-02, Published 2017-03-02
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摘要

The incidence and histological type of esophageal cancer are highly variable depending on geographic location and race/ethnicity. Here we want to determine if racial difference exists in the molecular features of esophageal cancer. We firstly confirmed that the incidence rate of esophagus adenocarcinoma (EA) was higher in Whites than in Asians and Blacks, while the incidence of esophageal squamous cell carcinoma (ESCC) was highest in Asians. Then we compared the genome-wide somatic mutations, methylation, and gene expression to identify differential genes by race. The mutation frequencies of some genes in the same pathway showed opposite difference between Asian and White patients, but their functional effects to the pathway may be consistent. The global patterns of methylation and expression were similar, which reflected the common characteristics of ESCC tumors from different populations. A small number of genes had significant differences between Asians and Whites. More interesting, the racial differences of COL11A1 were consistent across multiple molecular levels, with higher mutation frequency, higher methylation, and lower expression in White patients. This indicated that COL11A1 might play important roles in ESCC, especially in White population. Additional studies are needed to further explore their functions in esophageal cancer.

授权许可

Copyright © 2017 Shirui Chen et al. 2017
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

图表

Age-adjusted incidence rate of esophageal cancer by race. (a) and (b) are the incidence of esophageal squamous cell carcinoma (ESCC) and esophagus adenocarcinoma (EA) from 1992 to 2012. Three major races (White, Asian, and Black) were compared to investigate racial difference. (c) and (d) are the comparison of the esophageal cancer incidence among “SEER White,” “SEER Asian,” “Japan Asian,” and “China Asian”. Data of “Japan Asian” and “China Asian” were obtained from cancer surveillance programs in Japan [14] and China [15].

Age-adjusted incidence rate of esophageal cancer by race. (a) and (b) are the incidence of esophageal squamous cell carcinoma (ESCC) and esophagus adenocarcinoma (EA) from 1992 to 2012. Three major races (White, Asian, and Black) were compared to investigate racial difference. (c) and (d) are the comparison of the esophageal cancer incidence among “SEER White,” “SEER Asian,” “Japan Asian,” and “China Asian”. Data of “Japan Asian” and “China Asian” were obtained from cancer surveillance programs in Japan [14] and China [15].

Age-adjusted incidence rate of esophageal cancer by race. (a) and (b) are the incidence of esophageal squamous cell carcinoma (ESCC) and esophagus adenocarcinoma (EA) from 1992 to 2012. Three major races (White, Asian, and Black) were compared to investigate racial difference. (c) and (d) are the comparison of the esophageal cancer incidence among “SEER White,” “SEER Asian,” “Japan Asian,” and “China Asian”. Data of “Japan Asian” and “China Asian” were obtained from cancer surveillance programs in Japan [14] and China [15].

Age-adjusted incidence rate of esophageal cancer by race. (a) and (b) are the incidence of esophageal squamous cell carcinoma (ESCC) and esophagus adenocarcinoma (EA) from 1992 to 2012. Three major races (White, Asian, and Black) were compared to investigate racial difference. (c) and (d) are the comparison of the esophageal cancer incidence among “SEER White,” “SEER Asian,” “Japan Asian,” and “China Asian”. Data of “Japan Asian” and “China Asian” were obtained from cancer surveillance programs in Japan [14] and China [15].

Racial difference of somatic mutations in esophageal squamous cell carcinoma. (a) Mutation landscape of ESCC driver genes in 487 Asian and 42 White patients. (b) Difference of mutation frequencies between Asian and White patients. Red or green indicates higher mutation frequency in Whites or Asians, respectively. (c) Significantly racial difference in KEAP1 mutation frequency. (d) Racial difference in ESCC related pathways. ∗ indicates that the mutation frequency of this gene is significantly different between Asian and White patients.

Racial difference of somatic mutations in esophageal squamous cell carcinoma. (a) Mutation landscape of ESCC driver genes in 487 Asian and 42 White patients. (b) Difference of mutation frequencies between Asian and White patients. Red or green indicates higher mutation frequency in Whites or Asians, respectively. (c) Significantly racial difference in KEAP1 mutation frequency. (d) Racial difference in ESCC related pathways. ∗ indicates that the mutation frequency of this gene is significantly different between Asian and White patients.

Racial difference of somatic mutations in esophageal squamous cell carcinoma. (a) Mutation landscape of ESCC driver genes in 487 Asian and 42 White patients. (b) Difference of mutation frequencies between Asian and White patients. Red or green indicates higher mutation frequency in Whites or Asians, respectively. (c) Significantly racial difference in KEAP1 mutation frequency. (d) Racial difference in ESCC related pathways. ∗ indicates that the mutation frequency of this gene is significantly different between Asian and White patients.

Racial difference of somatic mutations in esophageal squamous cell carcinoma. (a) Mutation landscape of ESCC driver genes in 487 Asian and 42 White patients. (b) Difference of mutation frequencies between Asian and White patients. Red or green indicates higher mutation frequency in Whites or Asians, respectively. (c) Significantly racial difference in KEAP1 mutation frequency. (d) Racial difference in ESCC related pathways. ∗ indicates that the mutation frequency of this gene is significantly different between Asian and White patients.

Racial difference of DNA methylation in esophageal squamous cell carcinoma. (a) Number of genes whose methylations were significantly associated with race or other clinical variables. Statistical significance was defined as FC > 2 and P<0.05. (b) Volcano plot (log⁡2 fold change versus log⁡10P value) of differences in DNA methylation between Asian and White patients. Significant genes were colored with orange. (c) Heatmap of significantly differential DNA methylation between Asian and White patients.

Racial difference of DNA methylation in esophageal squamous cell carcinoma. (a) Number of genes whose methylations were significantly associated with race or other clinical variables. Statistical significance was defined as FC > 2 and P<0.05. (b) Volcano plot (log⁡2 fold change versus log⁡10P value) of differences in DNA methylation between Asian and White patients. Significant genes were colored with orange. (c) Heatmap of significantly differential DNA methylation between Asian and White patients.

Racial difference of DNA methylation in esophageal squamous cell carcinoma. (a) Number of genes whose methylations were significantly associated with race or other clinical variables. Statistical significance was defined as FC > 2 and P<0.05. (b) Volcano plot (log⁡2 fold change versus log⁡10P value) of differences in DNA methylation between Asian and White patients. Significant genes were colored with orange. (c) Heatmap of significantly differential DNA methylation between Asian and White patients.

Racial difference of gene expression in esophageal squamous cell carcinoma. (a) Number of genes whose expressions were significantly associated with race or other clinical variables. Statistical significance was defined as FC > 2 and P<0.05. (b) Volcano plot (log⁡2 fold change versus log⁡10 P value) of differences in gene expression between Asian and White patients. Significant genes were colored with orange. (c) Heatmap of significantly differential gene expression between Asian and White patients.

Racial difference of gene expression in esophageal squamous cell carcinoma. (a) Number of genes whose expressions were significantly associated with race or other clinical variables. Statistical significance was defined as FC > 2 and P<0.05. (b) Volcano plot (log⁡2 fold change versus log⁡10 P value) of differences in gene expression between Asian and White patients. Significant genes were colored with orange. (c) Heatmap of significantly differential gene expression between Asian and White patients.

Racial difference of gene expression in esophageal squamous cell carcinoma. (a) Number of genes whose expressions were significantly associated with race or other clinical variables. Statistical significance was defined as FC > 2 and P<0.05. (b) Volcano plot (log⁡2 fold change versus log⁡10 P value) of differences in gene expression between Asian and White patients. Significant genes were colored with orange. (c) Heatmap of significantly differential gene expression between Asian and White patients.

Racial difference of COL11A1 at multiple molecular levels. (a) Gene expression (P=0.01; FC = 3.31). (b) DNA methylation (P=0.003, FC = 0.63). (c) Frequency of somatic mutations (P=0.04). (d) Association between gene mutation and expression (P=0.03).

Racial difference of COL11A1 at multiple molecular levels. (a) Gene expression (P=0.01; FC = 3.31). (b) DNA methylation (P=0.003, FC = 0.63). (c) Frequency of somatic mutations (P=0.04). (d) Association between gene mutation and expression (P=0.03).

Racial difference of COL11A1 at multiple molecular levels. (a) Gene expression (P=0.01; FC = 3.31). (b) DNA methylation (P=0.003, FC = 0.63). (c) Frequency of somatic mutations (P=0.04). (d) Association between gene mutation and expression (P=0.03).

Racial difference of COL11A1 at multiple molecular levels. (a) Gene expression (P=0.01; FC = 3.31). (b) DNA methylation (P=0.003, FC = 0.63). (c) Frequency of somatic mutations (P=0.04). (d) Association between gene mutation and expression (P=0.03).

通讯作者

Hong Li.Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, cas.cn.lihong01@sibs.ac.cn

推荐引用方式

Shirui Chen,Kai Zhou,Liguang Yang,Guohui Ding,Hong Li. Racial Differences in Esophageal Squamous Cell Carcinoma: Incidence and Molecular Features. BioMed Research International ,Vol.2017(2017)

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