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

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

PROVIDER: PRJNA414233 | ENA |

REPOSITORIES: ENA

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

Project description: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.

2017-10-14 | GSE104958 | GEO

Association of immune related expression profile with sensitivity to neoadjuvant chemotherapy using docetaxel, cisplatin and 5-fluorouracil in esophageal squamous cell carcinoma.

Project description: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.

2023-11-15 | GSE225178 | GEO

Association of immune related expression profile with sensitivity to neoadjuvant chemotherapy using docetaxel, cisplatin and 5-fluorouracil in esophageal squamous cell carcinoma.

Project description:Association of immune related expression profile with sensitivity to neoadjuvant chemotherapy using docetaxel, cisplatin and 5-fluorouracil in esophageal squamous cell carcinoma.

| PRJNA934304 | ENA

Genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer

Project description:This SuperSeries is composed of the following subset Series: GSE25055: Discovery cohort for genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer GSE25065: Validation cohort for genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer Refer to individual Series

2011-05-11 | E-GEOD-25066 | biostudies-arrayexpress

Enhanced phosphorylation of c-Jun by cisplatin treatment as a potential predictive biomarker for cisplatin response in combination with patient-derived tumor organoids.

Project description:Despite recent advancement in sequencing technologies and large-scale drug screenings with hundreds of cell lines, the predictive accuracy of mutation-based biomarkers is still insufficient to guide cancer therapy. Therefore, novel types of diagnostic methods with alternative biomarkers are highly appreciated. To develop the novel methods, we hypothesized that sensitivity-specific changes in phosphorylations of signaling molecules could be useful as predictive biomarkers. Here, we aimed to develop predictive methods for cisplatin with a combination of such type of biomarker(s) and patient-derived tumor organoids (PDOs). We found that cisplatin sensitive cell lines or PDOs showed enhanced phosphorylation of c-Jun (p-c-Jun) within 24 h in response to cisplatin treatment. We also compared responses to cisplatin in 6 PDOs with therapeutic effect of neoadjuvant chemotherapy (docetaxel/cisplatin/5-fluorouracil) in 6 matched patients. Mechanistically, the c-Jun induction was partly related to TNF signaling induced by cisplatin. Thus, our data implicates the feasibility of enhanced p-c-Jun by cisplatin treatment as a predictive biomarker for the efficacy.

2023-06-01 | GSE186142 | GEO

Clinical response of metastatic gastric cancer patients to cisplatin and fluorouracil (CF) combination chemotherapy

2011-06-01 | GSE14208 | GEO

Transcription profiling of Brca1- and p53-deficient mouse mammary tumors to treatment with doxorubicin, docetaxel or cisplatin

Project description:We have studied in vivo responses of spontaneous Brca1- and p53-deficient mouse mammary tumors to treatment with doxorubicin, docetaxel or cisplatin.

2007-06-18 | E-NCMF-5 | biostudies-arrayexpress

Clinical response of metastatic gastric cancer patients to cisplatin and fluorouracil (CF) combination chemotherapy

Project description:This study was conducted to identify transcriptional profiles predictive of a clinical response of metastatic gastric cancer patients to cisplatin and fluorouracil (CF) combination chemotherapy. Endoscopic biopsy samples were collected from CF-treated metastatic gastric cancer patients prior to therapy and following the development of resistance to therapy.

2011-06-01 | E-GEOD-14208 | biostudies-arrayexpress

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

Project description:BackgroundRecently, 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 methodsA 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.ResultsSeventeen 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.ConclusionsA 17-molecule set that predicts pCR after NAC-DCF for locally advanced esophageal cancer was identified.

| S-EPMC5685591 | biostudies-literature

Tumor expression data from neoadjuvant trial of cisplatin monotherapy in triple negative breast cancer patients

Project description:Evidence suggests that BRCA1 mutation associated tumors have increased sensitivity to DNA damaging agents like cisplatin. Sporadic triple negative breast cancers (TNBC) have many phenotypic similarities to BRCA1 tumors and may have a similar sensitivity to cisplatin. We tested the efficacy of cisplatin monotherapy in 28 TNBC patients in a single arm neoadjuvant trial with outcome measured by pathologic treatment response quantified using the Miller-Payne scale. We used microarrays gene expression profiles to determine tumor subtype of each trial tumor sample and to test various expression signatures for association with pathologic response to cisplatin.

2009-11-04 | GSE18864 | GEO

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