Microarray gene expression analysis of chemosensitivity for docetaxel,cisplatin and 5-fluorouracil(TPF)combined chemotherapeutic regimen in hypopharyngeal squamous cell carcinoma

Objective: To screen out a set of candidate genes which could help to determine whether patients with hypopharyngeal squamous cell carcinoma (HSCC) could benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy. Methods: Gene-expression profiles in 12 TPF-sensitive patients were compared to 9 resistant controls by microarray analysis. Subsequently, expression levels of potential biomarkers in chemosensitive cell line FaDu after TPF treatment were observed by quantitative real-time polymerase chain reaction (qRT-PCR). Results: Through microarray analysis, 1,579 differentially expressed genes were identified, of which 815 were up-regulated in TPF chemotherapy-responsive tissues whereas 764 were down-regulated. Gene ontology (GO) analysis suggested these genes participating in physiological processes including transcription and its regulation, cellular signal transduction and metabolic process. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) database revealed that MAPK and Jat/STAT signaling pathways occupied important roles in TPF chemotherapeutic sensitivity. Moreover, in vitro cell culture experiments revealed the expression alternations of IL-6, MAPK14, JUN, CDK5 and CAMK2A exposed to TPF treatment by qRT-PCR, whilst providing an insight into the mechanism underlying TPF chemotherapeutic response in HSCC. Conclusions: These results provided a battery of genes related to TPF chemotherapeutic sensitivity and might act as molecular targets in HSCC treatment. Moreover, these candidate biomarkers could contribute to HSCC individualized treatment.

Screening of molecular markers of induced chemotherapy in supraglottic laryngeal squamouscell carcinoma

Objective:To investigate the expressions of MAPK10,c-Jun and Itga6 in laryngeal carcinoma and its influence on the sensitivity to docetaxel,cisplatin and 5-fluorouracil(TPF)chemotherapy.Methods:Fifty-seven patients with supraglottic squamous cell carcinoma,who were treated by two cycles of TPF induction chemotherapy in our hospital,were enrolled in this study and divided into groups by chemotherapy resistance or chemotherapy sensitivity.The expressions of mRNA and protein of MAPK10,c-Jun and Itga6 in tumor tissues were evaluated by immunohistochemistry.The consistency of mRNA and protein expressions was tested,and the relation with the clinicopathological features was analyzed.Results:The positive rates of MAPK10 andc-Jun in the tumor tissues of the sensitive group were significantly higher than those of there assistant group,which was 90.48%and 100.00%,respectively.The expression rate of Itga6 was significantly higher in the resistant group,which was 83.33%(P<0.05).The mRNA levels of MAPK10 and c-Jun were significantly lower in the resistant group than in the sensitive group,whilethemRNA levelof Itga6was significantly higher in the resistant group(P<0.05).The protein expressions of MAPK10,c-Jun and Itga6 were consistent with their mRNA expressions(P<0.05).The expressions of MAPK10,c-Jun and Itga6 were not correlatedwithage,gender and tumor diameter(P>0.05).However,the expressions of MAPK10 and c-Jun were negatively correlated withclinical stage and pathological grading(P<0.05).Negative correlations between MAPK 10 and Itga6,and between c-Jun and Itga6in tumor tissues were found by Spearman’srank correlation coefficient(P<0.05).The correlation was also negative in the resistant tumor tissues(P<0.05).Conclusion:The MAPK10 and c-Jun expressions were down-regulated,while the Itga6 expression was up-regulated in the chemo-resistant laryngeal carcinoma,and the expression levels of different factors were correlated witheach other.These factorsmight be important biomarkers for predicting outcomes of TPF chemotherapy in laryngeal carcinoma in the future.