And Its Clinical Correlation Between Esophageal And Lung Cancer Primary Tumor Xenograft Model

Background and Objective Xenograft model is an important tool in cancer research. This study is to establish a platform of patient-derived esophagus cancer, cardiac cancer and lung cancer xenograft model in nude mice and to investigate the correlation between clinical characteristics and the xenograftability of the maligancies.Methods Surgically resected esophagus cancer, cardiac cancer and lung cancer specimens were implanted subcutaneously in nude mice. The xenograft tumors were surgically removed when they reach approximately l-2cm3in volume, and passaged to new nude mice. The growth process and histological property of the xenograft tumors were observed. Statistical analysis was taken to investigate the relationship between clinical characteristics and xenograftability.Results140esophagus squamous cell carcinoma(ESCC),122cardiac cancer and368lung cancer were implanted and the engraftment rates were32.1%,15.6%and27.4%respectively. Tumor grafts replicated the primary tumors histologically. Exon-sequencing of the primary ESCC and correspondent xenograft tumor showed that the xenograft tumor retained nearly90%of the somatic mutations of the primary tumor. In vivo pharmacodynamic test showed that the tumor volumn of ESCC-bearing nude mice treated with5-Fu, Cisplatin, and Gemcitabine grew more slowly than those of control group. The average weight of tumors from the treated mice are lower than that of control group. Lung-cancer-bearing mice had similar react to Paclitaxel, Cisplatin, and Gemcitabine. The engraftment rate of Cardiac cancer (adenocarcinoma) is significantly lower than that of ESCC(P=0.002). In non-small cell lung cancer (NSCLC), the engraftment rate of squamous cell carcinoma is significantly higher than that of adenocarcinoma (P<0.001); the malignancies derived from male, smokers have higher rate of engraftment than those from female, non-smokers (both with p value<0.001). The engraftment rate rises with T stage of the primary tumor(P<0.001) and TNM stage I tumors have significantly lower engraftment rate than tumors of others stages(P<0.05). In lung adenocarcinoma, the relation between xenograftability and gender, smoking, and TNM staging is similar with that in NSCLC. In lung squamous cell carcinoma however, the effcect of T and TNM staging of primary tumor on xenograftability is not obviousConclusion The xenograft models were successfully established for patient-derived ESCC, cardiac cancer and lung cancer in immune deficient mice. This model system replicates the biological characteristics of their human origins. The xenograftability of squamous cell carcinoma is significantly higher than that of adenocarcinoma. The xenograftability of NSCLC is related to gender, smoking, T staging and TNM staging of the primary tumor.