Relationship Between Molecular Characteristics, Clinicopathological Features And Progression Free Survival Of Colorectal Cancer

ObjectiveTo analyze the relationship between molecular characteristics?clinicopath--ological features and progression free survival?PFS?of colorectal cancer?CRC?patients and aim to provide prognostic marker and individualized treatment for CRC patients.MethodsA total of 224 CRC patients who did next generation sequencing?NGS?in the first affiliated hospital of Zhengzhou University were enrolled in the study.The clinicopathological data and NGS results were retrospective collected.The?² test was used to analyze the relationship between common mutation genes such as KRAS?NRAS?BRAF?TP53?PIK3CA?SMAD4?APC?POLE?ATM?EGFR?SOX?PTEN and clinicopathological features such as gender?age?primary tumor location?staging and so on.The relationship of clinicopathological features?gene mutations such as KRAS?TP53?APC?PIK3CA?SMAD4?POLE?PTEN and PFS in 106metastatic colorectal cancer?mCRC?patients who had been received fist-line treatment for their advanced disease and had survival data were analyzed by Cox regression.Results1.We discovered mutations that were previously rarely reported:such as missense mutations in the codons of BRAF 462?466?485?547?597?762 and insertion mutations in the first exon p.33₃4insGA.One patient had BRAF and NRAS co-mutations.2.APC mutation rates in male patients was significantly higher than that in female patients,which were 54.76%?69/126?and 40.82%?40/98?,respectively?P<0.05?.3.The location of metastasis were related to the mutation sites:patients of abdominal metastasis with APC wild type had significantly higher rate than those patients who had APC mutant type,and the incidence was 84.62%?11/13?and15.38%?2/13?,respectively?P<0.05?;Patients of lung metastasis with KRAS mutant had significantly higher rate than those with wild type,and the incidence was 61.36%?27/44?and 38.64%?17/44?,respectively?P<0.05?.4.There were significant differences in gene mutation rates in CRC patients with different primary tumor location:there were more mutations in the right colon.The expression of right-sided CRC patients was higher of PIK3CA?ATM?PTEN than left-sided cancers?P<0.05?.And PIK3CA mutation rates were 16.03%?21/131?and32.26%?30/93?in left-sided and right-sided;ATM mutation rates were 5.34%?7/131?and 12.9%?12/93?,respectively;PTEN mutation rates were 1.53%?2/131?and9.68%?9/93?,respectively.But the expression of TP53 in left-sided was significantly higher than that of the right-sided?P<0.05?.The mutation rates in left-sided and right-sided tumors were 73.28%?96/131?and 50.54%?47/93?,respectively.5.Gene mutation status of POLE and KRAS were related with TNM stage:the mutation rate of POLE in stage I and II patients was significantly higher than that in stage III and IV patients,the mutation rates were 15.91%?7/42?and 3.89%?7/182?,respectively?P<0.05?;The mutation rate of KRAS in patients with stage III and IV was 48.33%?87/182?,and 31.82%?14/42?in stage I and II,the mutation rate in stage III and IV was significantly higher than that in the stage I and II?P<0.05?.6.Median PFS?mPFS?for mCRC patients was 9.0 months.And mPFS for patients with left-sided and right-sided tumors was 10.0 and 7.7 months,respectively.Patients with left-sided tumors had superior mPFS?left-sided vs right-sided:HR=1.644,95%CI=1.091 to 2.477,P<0.05?.PFS for patients with total variants number?3 was significantly longer than with>3?HR=1.577,95%CI=1.040 to2.391,P<0.05?.Right-sided primary tumors and total variant numbers>3 were independent predictors of shorter PFS.No significant relationship was identified between gene mutation status of KRAS?TP53?APC?PIK3CA?SMAD4?POLE?PTEN and PFS?P>0.05?.Conclusions1.APC mutation rates in male patients was significantly higher than that in female patients.2.Patients with KRAS mutation was significantly higher lung metastasis than with wild,and the mutation rate in stage III and IV was significantly higher than that in the stage I and II.But the mutation rate of POLE in stage I and II patients was significantly higher than that in stage III and IV patients.3.Right-sided cancers expressed higher levels of PIK3CA?ATM?PTEN than left-sided cancers.Left-sided cancers significantly expressed higher levels of TP53than that in the right-sided.4.Right-sided primary tumors and total variants number>3 were independent predictors of shorter PFS.