| BackgroundColorectal cancer is a common malignant tumor in the worldwide,and liver was the main target organ for metastasis of colorectal cancer.Although the vital value of surgical treatment for hepatic metastases has been established,only 10-20% of the patients are eligible for radical surgical indications.In recent years,increasingly mature experience of interventional treatment for liver metastasis.Selective transcatheter arterial chemoembolization(TACE)has also obtained encouraging data tumor curative effect(technology,security and efficacy)in the treatment of colorectal cancer liver metastases(CRLM).Oligometastasis is an intermediate state from primary tumor to distant metastasis,and is a stable state of distant metastasis of malignant tumors,often with organ specificity.In 2016,the concept of "oligometastasis" was first introduced in the diagnosis and treatment guidelines for colorectal cancer by European Society for Medical Oncology(ESMO).Here,the importance of "local damage treatment(LDT)" in the treatment of oligometastasis diseases was emphasized especially.Interventional therapy,including conventional TACE has played an important role in colorectal cancer liver metastasis.Hence,we speculate that,as a kind of local treatment,TACE may also play an important role in the topical treatment of CRC liver oligometastasis.Here,this study focused on the clinical efficacy and prognosis of TACE in the treatment of CRC liver oligometastasis,with a view to providing new ideas for clinical treatment of liver oligometastasis of colorectal cancer.Epigenetic anomaly(DNA methylation,histone methylation,histone acetylation and non-coding RNA regulation,etc.)is closely related to the occurrence of colorectal cancer liver metastasis.This study discussed the role of histone modification in colorectal cancer liver metastasis,with the perspective for providing a new strategy for the diagnosis and treatment of colorectal cancer liver oligometastasis.Objectives1.To analyze the clinical efficacy of TACE in the treatment of colorectal cancer liver oligometastasis;and explore its prognostic factors;2.To observe the expression and clinical significance of H2 Bub,H3K9me3 and H3K27me3 in the metastasis of colorectal cancer.Methods1.A retrospective case-control analysis was conducted for the analysis of clinical effect differences between colorectal cancer liver oligometastasis and extensive metastasis.Comparisons of image characteristics,tumor biomarkers,neutrophil counts and percentage,tumor local response rate,progression-free survival(PFS),overall survival(OS),survival from liver metastasis and overall survival after interventional therapy among different groups were also conducted.The survival prognosis factors were analyzed by univariate and multifactor analysis.2.Immunohistochemical staining was adopted for the detection of H2 Bub,H3K9me3 and H3K27me3 expression.A comparative analysis of H2 Bub,H3K9me3 and H3K27me3 expression between colorectal cancer and benign lesions tissues was conducted.The differences of H2 Bub,H3K9me3 and H3K27me3 expression among different metastasis were also assessed.The relationships between H2 Bub,H3K9me3 and H3K27me3 expression and clinical pathological parameters were also conducted in this study.Finally,the prognosis value of H2 Bub,H3K9me3 and H3K27me3 in CRLM was also explored.Results1.The difference of blood supply for tumor between colorectal cancer liver oligometastasis and extensive metastasis was not significant(P > 0.05).Likewise,the difference of blood supply between simultaneous metastases and metachronous metastasis was also not significant(P > 0.05).The difference of blood supply between liver multi-metastasis and extensive metastasis was also not significant(P > 0.05).2.The relationship between iodized oil consumption and tumor volume by CT measurement was positive(r=0.58,P=0.02)in simultaneous liver oligometastasis group.Similarly,a strong correlation between sum of tumor diameters by CT measurement and DSA measurement in simultaneous liver oligometastasis group was found in this study(r=0.87,P<0.001).In both simultaneous liver oligometastasis group and metachronous metastasis group,the strong correlation between tumor volume by DSA radiography and embolism area was also found(r = 0.93,P<0.001).r =0.84,P<0.001).However,there was no significant correlation in liver multiple metastasis group and extensive metastasis group(P >0.05).3.There were no significant differences of CEA,CA 199,AFP and VEGF level between liver multiple metastasis group and extensive metastasis group(P >0.05).The differences of that among four groups were also not significant(P >0.05).4.There were no significant differences of neutrophil counts and percentage between liver multiple metastasis group and extensive metastasis group(P >0.05).The differences of that among four groups were also not significant(P >0.05).5.The overall survival of patients with colorectal cancer liver metastasis was 28.6 months(95% CI: 18.5 ~ 38.7 months),and the 1 year,2 year and 3 year survival rate was 94.9%,63.1% and 34.9% respectively.The median progress free survival was 10.0 months(95% CI: 7.8 months ~ 12.2 months),and the 1 year,2 year and 3 year progress free survival rate was 40.5%,25.8% and 8.1% respectively.The median survival time after liver metastasis was 19.0 months(95% CI: 14.6 months ~ 23.4 months);and the median survival time after interventional therapy was 17.0 months(95% CI: 13.7 months ~ 20.3 months).6.There was a significant difference in overall survival after interventional therapy in patients with liver oligometastasis group and extensive metastasis group(P=0.002),with the median time of 22.0 months and 10.0 months respectively.The overall survival after interventional therapy in patients with simultaneous liver oligometastasis group,metachronous metastasis group,liver multi metastasis group and extensive metastasis group was different(P = 0.001),with the median time of 22.0 months,22.0 months,15.0 months and 7.0 months respectively.7.In univariate analysis,the median overall survival of patients with primary lesion resection was longer than that of unresection group(33.2 months vs 17.6 months,P<0.05).Likewise,the median overall survival of patients with liver metastasis lesion resection was longer than that of unresection group(34.0 months vs 17.0 months,P=0.042).The local tumor response,local ablation treatment,chemotherapy cycles and interventional therapy cycles were not the prognosis of overall survival.8.In multifactor analysis,liver metastasis resection(HR 7.034;95% CI: 1.921 ~ 25.761;P=0.003)and liver oligometastasis(HR 0.244;95%CI: 0.088~0.675,P=0.007)were the independent predictor of overall survival.In other words,the risk of death in liver metastasis unresection group was 7.034 times than that of liver metastasis resection group,and the risk of death in liver oligometastasis group was 0.244 times than that of extensive metastasis group.9.The expression of H2 Bub,H3K9me3 and H3K27me3 in colorectal cancer tissue was significantly lower than that of non tumor tissues,and the expression level in non-metastasis colorectal cancer group was higher than that in simultaneous liver oligometastasis group,and higher than that in extensive group.10.H2 Bub expression was related to tumor staging,and the expression of H3K27Me3 was related to lymph node metastasis.11.The expression of H2 Bub in colorectal cancer tissues was related to H3K9me3 and H3K27me3 expression.12.The overall survival of H2 Bub negative patients was significantly better than that of H2 Bub positive patients.Conclusions1.Compared with extensive metastasis group,patients in liver oligometastasis were more likely to benefit from interventional therapy.There was a poor survival after interventional therapy in extensive metastasis group.The median overall survival of the primary lesion resection group was better than that of the unresection group.And the median overall survival of liver metastasis resection group was better than that of unresection group.Both of liver metastasis resection and liver oligometastasis were the independent predictors of overall survival.2.The expression of H2 Bub,H3K9me3 and H3K27me3 in colorectal cancer tissue was significantly lower than that of non tumor tissues,and the expression level in non-metastasis colorectal cancer group was higher than that in simultaneous liver oligometastasis group,and higher than that in extensive group.3.H2 Bub expression was related to tumor staging,and the expression of H3K27Me3 was related to lymph node metastasis.The overall survival of H2 Bub negative patients was significantly better than that of H2 Bub positive patients.H2 Bub is expected to be a novel biomarker for early diagnosis,treatment and prognosis of colorectal cancer. |
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