Esophageal squamous cell carcinomas with distinct invasive depth show different gene expression profiles associated with lymph node metastasis

Abstract

Abstract. We examined the gene expression profiles of esophageal squamous cell carcinomas (ESCCs) with respect to degree of invasive depth and lymph node (LN) involvement in a large cohort. We used high-density oligonucleotide microarrays to examine the expression of 22,115 genes in 54 ESCCs and 11 non-cancerous esophageal tissues. We found that 4,155 genes were biologically significant in both ESCC and non-cancerous esophageal tissue by analysis of Present Call (hybridization quality by Affymetrix) throughout all samples. From these genes, we used a supervised learning method to select genes responsible for the development of ESCC. We found that 999 genes were expressed differentially in pT1/pN0 tumors vs. non-cancerous esophageal tissue. In the same manner, 48, 66 and 30 genes were expressed differentially in pT1/pN0 tumors vs. pT1/pN1 tumors, pT1/pN0 tumors vs. pT2-4/ pN0 tumors and pT2-4/pN0 tumors vs. pT2-4/pN1 tumors, respectively. Intriguingly, there were no overlaps between the 48 LN metastasis-related genes of pT1 tumors and the 30 LN metastasis-related genes of pT2-4 tumors, suggesting that ESCCs with distinct invasive depths express different genes linked to LN metastasis. Our present results suggest that the degree of invasive depth must be considered when predicting LN metastasis of ESCC from gene expression profiles.

Global Gene Expression Profiling and Validation in Esophageal Squamous Cell Carcinoma and Its Association with Clinical Phenotypes

“…Several recent studies analyzed gene expression profiling for ESCC (22-25). One study also used Affymetrix chips but studied only 15 ESCC cases (24), while other studies applied cDNA microarrays with Cy3 or Cy5 labeling that examined more limited numbers of genes (22;23).…”

“…One study also used Affymetrix chips but studied only 15 ESCC cases (24), while other studies applied cDNA microarrays with Cy3 or Cy5 labeling that examined more limited numbers of genes (22;23). The largest number of ESCC cases studied was a Japanese report of 54 cases examined with the Affymetrix Human U133 A chip; however, pair-matched normal tissues were not used in that study (26).…”

Molecular factors related to metastasis of esophageal squamous cell carcinoma

“…Intriguingly, there was no overlap between the 48 genes related to lymph node metastasis of pT1 tumors and the 30 genes related to lymph node metastasis of pT2-4 tumors, suggesting that ESCCs with different levels of invasiveness expressed different genes linked to lymph node metastasis. This result suggests that the depth of invasion must be considered when attempting to predict nodal metastasis of ESCC from the gene expression profi le [118].…”

“…Another study showed that 4155 genes were biologically signifi cant in both ESCC and noncancerous esophageal tissue by Present Call analysis (hybridization by Affymetrix) [118]. A supervised learning method was used to select genes responsible for the development of ESCC.…”

cDNA microarray analysis of esophageal cancer: discoveries and prospects

“…40 There was no overlap between the 48 genes related to lymph node metastasis of pT1 tumors and the 30 genes related to lymph node metastasis of pT2-4 tumors, suggesting that ESCCs with different levels of invasiveness express different genes linked to nodal metastasis. 41 The infl uence of stromal cells as well as the depth of invasion must be considered when attempting to predict lymph node metastasis of ESCC based on the gene expression profi le.…”