Association of immune related expression profile with sensitivity to neoadjuvant chemotherapy using docetaxel, cisplatin and 5-fluorouracil in esophageal squamous cell carcinoma.
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ABSTRACT: Neoadjuvant chemotherapy (NAC) followed by surgery is one of the standard therapeutic approaches for patients with locally advanced esophageal carcinoma in Japan. Recently, JCOG1109 study revealed that NAC with docetaxel, cisplatin and 5-fluorouracil (5-FU) (DCF-NAC) is superior to NAC with cisplatin and 5-FU, and has become the standard preoperative chemotherapy. By using microarray, we have previously investigated expression profiles of endoscopic biopsies of patients with esophageal squamous cell carcinoma (ESCC) before DCF-NAC (preNAC) and identified 17 molecules as predictive biomarkers for pathologically complete response to DCF-NAC. Here, we re-grouped our previous dataset based on the histopathological response grade with an addition of several microarray profiles (altogether 5 non-tumors, 12 highly resistant cancers and 27 sensitive cancers) and re-analyzed by bioinformatic web tools, including DAVID, GSEA, UALCAN and CIBERSORTx. We identified 204 genes as differentially expressed genes (DEGs) between highly resistant and sensitive groups. A number of DEGs were related to immune response and expressed higher in sensitive group. By UALCAN, 28 of the top 50 DEGs showed that their high expression were associated with favorable prognosis (p<0.25). Among them, 18 DEGs reached significance (p<0.05), suggesting that patients with high expression of these genes might have benefited from chemotherapy and thus had better outcome. We further showed distribution of the cells expressing CXCL9 mRNA, one of the prognosis related DEGs, in preNAC biopsy tissues of DCF-sensitive case. In conclusion, our data may provide useful information to establish predictive and effective methods for DCF-NAC in ESCC.
ORGANISM(S): Homo sapiens
PROVIDER: GSE225178 | GEO | 2023/11/15
REPOSITORIES: GEO
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