A 17-molecule set as a predictor of complete response to neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in esophageal cancer

Abstract

Background: Recently, neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil (NAC-DCF) was identified as a novel strong regimen with a high rate of pathological complete response (pCR) in advanced esophageal cancer in Japan. Predicting pCR will contribute to the therapeutic strategy and the prevention of surgical invasion. However, a predictor of pCR after NAC-DCF has not yet been developed. The aim of this study was to identify a novel predictor of pCR in locally advanced esophageal cancer treated with NAC-DCF.

Patients and methods: A total of 32 patients who received NAC-DCF followed by esophagectomy between June 2013 and March 2016 were enrolled in this study. We divided the patients into the following 2 groups: pCR group (9 cases) and non-pCR group (23 cases), and compared gene expressions between these groups using DNA microarray data and KeyMolnet. Subsequently, a validation study of candidate molecular expression was performed in 7 additional cases.

Results: Seventeen molecules, including transcription factor E2F, T-cell-specific transcription factor, Src (known as "proto-oncogene tyrosine-protein kinase of sarcoma"), interferon regulatory factor 1, thymidylate synthase, cyclin B, cyclin-dependent kinase (CDK) 4, CDK, caspase-1, vitamin D receptor, histone deacetylase, MAPK/ERK kinase, bcl-2-associated X protein, runt-related transcription factor 1, PR domain zinc finger protein 1, platelet-derived growth factor receptor, and interleukin 1, were identified as candidate molecules. The molecules were mainly associated with pathways, such as transcriptional regulation by SMAD, RB/E2F, and STAT. The validation study indicated that 12 of the 17 molecules (71%) matched the trends of molecular expression.

Conclusions: A 17-molecule set that predicts pCR after NAC-DCF for locally advanced esophageal cancer was identified.

Fig 1. Color mapping of molecular expressions on KeyMolnet.

Seventeen molecules were included in KeyMolnet. Red nodes indicate higher expression in the pCR group. Blue nodes indicate lower expression in the pCR group. The color shades are correlated with the expression levels of the molecules.

Fig 2. Comparison of candidate molecular expressions between extracted cases and validation cases.

Of the 17 molecules, 12 (71%) (bold) matched the trends of molecular expression.