Research In Prognostic Value On Expression Of Angiogenic-related Factors In Serum Of Patients With Metastatic Colorectal Cancer

Objective: To summarized clinical characters and features and survival of metastaticcolorectal cancer.To investigate the level of VEGF-A, VEGF-B, VEGFR-2, sTRAILand VEGF in the serum of metastatic colorectal cancer, and to explore the relationshipof serum levels of VEGF-A, VEGF-B, VEGFR-2, sTRAIL,VEGF andclinicopathological features. To find a possible predictive marker of the serum ofmetastatic colorectal cancer that could be used to predict the effect of bevacizumab.Methods: Patients with metastatic colorectal cancer in our hospital from Dec.2010toMar.2013were analyzed with their clinical clinicopathological and treatment features.All patients were separated to bevacizumab-group and chemotherapy-group accordingto their treatment features. To detect the expression of VEGF-A, VEGF-B, VEGFR-2,sTRAIL and VEGF in the serum of all90patients before first-line therapy and after6weeks of first-line therapy. To explore the relationship between the serum level ofVEGF-A, VEGF-B, VEGFR-2, sTRAIL, VEGF and clinicopathological features. Tocompare the differences of VEGF-A, VEGF-B, VEGFR-2, sTRAIL, VEGF in serumlevel before first-line therapy and after6weeks of first-line therapy. To compare thedifferences of VEGF-A, VEGF-B, VEGFR-2, sTRAIL and VEGF in serum levelbetween bevacizumab-group and chemotherapy-group. To exam the relationshipbetween VEGF-A, VEGF-B, VEGFR-2, sTRAIL and VEGF, analyse their relationshipwith survival.Results:1. At the end of the follow-up（Mar.30th,2013）,51patients exhibitedprogression (56.7%) and10(11.1%) patients died.34(37.8%) achieved partialresponse (PR) and34patients (37.8%) had stable disease (SD), exhibited an ORR of37.8%, and a DCR of75.6%. Among32patients in bevacizumab-group,14patients achieved partial response (PR),（43.7%）,34(37.8%) had stable disease (SD),17(29.3%) had progression diease (PD).Among58patients in chemotherapy-group,20patients achieved partial response (PR)（34.5%）,21(36.3%) had stable disease (SD),17(29.3%) had progression diease (PD).90patients with mCRC were collected,51(56.7%) patients were suffered from progression-disease(PD),10(11.1%) patientsdied, progression free survival(mPFS) were8.37months, the the median overallsurvival(mOS) was not available.2. There were32(35.6%) patients in bevacizumab-group, mPFS was11.73months.Fifty-eight patients in chemotherapy-group, mPFS was8.00. Differencebetween mPFS of bevacizumab-group and chemotherapy-group was significant（P=0.042）. Metastasis to lymph gland and KRAS gene status were independentprognostic factor of PFS（P<0.05）.3. The serum level of VEGF-A, VEGF-B, VEGFR-2, sTRAIL and VEGF in90patients before first-line therapy was316.9±16.21ng/l,268.2±10.3ng/l,10.3±0.5ng/ml,1521.1±76.3ng/l and924.2±46.3ng/l respectively. The serum level ofVEGF-A, VEGF-B, VEGFR-2, sTRAIL and VEGF in90patients after6weeks offirst-line therapy was323.6±15.5ng/L,238.5±10.6ng/L,10.0±0.5ng/ml,1494.8±61.7ng/L and956.1±50.9ng/L respectively. The level of VEGF-A, VEGF-B,VEGFR-2, sTRAIL and VEGF had no significant difference before first-line therapyand after6weeks of first-line therapy (P>0.05).4. The serum level of VEGF-A, VEGF-B, VEGFR-2, sTRAIL and VEGF inbevacizumab-group after6weeks of first-line therapy was300.3±25.4ng/L,246.1±16.7ng/L,9.73±0.68ng/ml,1461.3±116.4ng/L and974.9±85.5ng/L,respectively. The serum level of VEGF-A, VEGF-B, VEGFR-2, sTRAIL and VEGF inchemotherapy-group after6weeks of first-line therapy was338.8±19.2ng/L,233.6±13.9ng/L,10.6±0.72ng/ml,1516.6±113.6ng/L and913.8±64.7ng/L,respectively. There was no significant difference between bevacizumab-group andchemotherapy-group (P>0.05).5. Patients in bevacizumab-group were serapated to PD-group and PR+SD-groupaccording to the effect of treatment. The serum levels of sTRAIL were 1423.2±111.2ng/l and1696.9±149.1ng/l before first-line therapy and after6weeks offirst-line therapy in PR+SD-group, difference was significant（P=0.048）. Thisindicated the variation of serum level of sTRAIL may relate to the effect ofbevacizumab. There was no significant difference in the serum level of VEGF-A,VEGF-B, VEGFR-2and VEGF before first-line therapy and after6weeks of first-linetherapy in PR+SD-group (P>0.05).6. Analyse the relationship between VEGF-A, VEGF-B, VEGFR-2, sTRAIL, VEGFand effect of bevacizumab before first-line therapy and after6weeks of first-linetherapy. Effect of patients with lower level of sTRAIL in serum tend to be better thanpatients with higher level of sTRAIL（P=0.036）, which indicated lower level ofsTRAIL in serum may related to the effect of bevacizumab. There was no significantdifference in the serum level of VEGF-A, VEGF-B, VEGFR-2and VEGF beforefirst-line therapy and after6weeks of first-line therapy (P>0.05).Conclusion:1.Patients with metastatic colorectal cancer treated by bevacizumab hadlonger PFS than patients only treated by chemotherapy;2.There was no significantdifference between the serum level of VEGF-A, VEGF-B, VEGFR-2, sTRAIL andVEGF and clinicopathological features.3. The serum level of sTRAIL increased after6weeks of first-line therapy in PR+SD-group（P=0.048）, that indicated the variation ofserum level of sTRAIL may related to the effect of bevacizumab.4. Effect of patientswith lower level of sTRAIL in serum tend to be better than patients with higher levelof sTRAIL（P=0.036）.