| BackgroundColorectal cancer(CRC)is a common gastrointestinal tumor in China.In recent years,the incidence of CRC has been increasing year by year,and the age of onset has become younger and younger.Liver is a common site of advanced CRC metastasis,and oxaliplatin based systemic chemotherapy is the main chemotherapy regimen for CRC liver metastasis.However,drug resistance inevitably occurs in most patients during chemotherapy,and overcoming drug resistance is an urgent problem in advanced CRC treatmentHomeobox genes(HOX genes)are an important family of genes that regulate embryonic development,cell growth and differentiation.In recent years,researchers have found that HOXA9 gene is closely related to the occurrence and development of tumors.Some studies have confirmed the abnormal expression of HOXA9 in the liver metastasis of colon cancer and primary colon cancer,and found that the expression of HOXA9 is higher in colon cancer with worse differentiation,later TNM stage and earlier lymph node metastasis.In addition,studies have found that the expression of HOXA9 gene is affected by chemotherapy drugs,and the expression level of HOXA9 gene is related to the therapeutic effect of tumor.However,it has not been reported whether oxaliplatin resistance can change the protein level of HOXA9 in CRC liver metastasis and whether the protein level of HOXA9 can be used as a predictor of chemotherapy efficacy.ObjectiveThis project aims to understand whether there is a difference in HOXA9 gene expression and biological characteristics of HT29 cells and HT29/OXA cells,to explore whether the expression of HOXA9 in CRC liver metastasis related to oxaliplatin-resistant and progression-free survival,to determine whether the level of HOXA9 protein in the liver before chemotherapy can be used as a predictor of the therapeutic effect of oxaliplatin combined with bevacizumab in patients with liver metastasis of colon cancer.MethodsThis project is divided into two parts,the first part is the foundation part,colon cancer cells(HT29)and oxaliplatin-resistant colon cancer cells(HT29/OXA)as the research objects,flow cytometry analyse the HOXA9 gene expression between HT29 cells and HT29/OXA cells,to observe morphology and growth characteristics of HT29/OXA and HT29 cells by optical microscope,and to compare cloning formation between HT29 cells and HT29/OXA cells.To research biological characteristics between HT29 cells and OXA/HT29 cells,and the expression of HOXA9 situation.The second part is clinical study part.A prospective,single-center,small-sample clinical study was conducted in advanced inoperable right colon cancer with liver metastasis(KRAS-wild),those patients who are treated by FOLFOX or CapeOx combine with bevacizumab,HOXA9 protein expression level in liver metastatic tissue specimens were detected by immunohistochemistry before and after chemotherapy.Results1.The morphological and growth characteristics of HT29 cells and HT29/OXA cells are different.HT29/OXA cells were large and heterogeneous,have a longer doubling time(29.26 h VS 22.53h)and more slow growth rate,and the clone formation rate((39.32±2.21)%VS(26.59±2.42)%)and HOXA9 expression level((41.44± 1.12)%VS(31.61 ± 1.42)%)of HT29/OXA cells were higher compared with HT29 cells2.The expression of HOXA9 in liver metastasis of colon cancer before chemotherapy was not correlated with gender,age,histological grade or lymph node metastasis(P>0.05)3.The patient who is progression after oxaliplatin-containing regimen combined with bevacizumab,the high expression rate of HOXA9 in intrahepatic tissue higher than before treat:ment(77.27%VS 45.45%)(P<0.05),the patient who is hepatic progression,the high expression rate of HOXA9 in intrahepatic higher than before treatment(93.75%VS 50%)(P<0.05),while the patient who without hepatic progress,the high expression rate of HOXA9 in intrahepatic is no obvious change before chemotherapy(33.33%VS 33.33%)(P>0.05).4.The level of HOXA9 before chemotherapy was not correlated with the progression-free survival time of patients(P>0.05).ConclusionsHOXA9 is associated with oxaliplatin resistance in colon cancer.Oxaliplatin resistance may promote the expression of HOXA9 protein in tissues,but this promotion is mainly reflected in progressive target lesions.Single HOXA9 protein levels in liver metastases before chemotherapy could not be used as a predictor of the efficacy of oxaliplatin-containing regimen(FOLFOX or CapeOx)combined with bevacizumab in the treatment of colon cancer liver metastasis. |
