Early Diagnosis Of De Winter Syndrome And Clonal Origin Of Recurrent Hepatocellular Carcinoma

Object Early diagnosis plays a critical role in making clinical decision and choosing proper treatment.Early diagnosis has two main methods: diagnosis using medical equipment and identification of biolmarkers with clinical specificity.Early diagnosis of de Winter syndrome and recurrent hepatocellular carcinoma(RHCC)clones origin can effectively help doctors implement clinical decisions.Characteristic electrocardiogram(ECG)is used mainly for early diagnosis of de Winter syndrome at present,but RHCC clones origin currently lacks ideal biomarkers.De Winter syndrome is an extremely rare but fatal acute anterior wall myocardial infarction that occurs mostly in young male patients.De Winter syndrome is dangerous and easy to miss the best treatment time because of mis-diagnosis.Hepatocellular carcinoma(HCC)represents the third leading cause of cancer-related deaths in China,with high recurrence and poor prognosis.RHCC is derived from two different mechanisms: 1)intrahepatic metastasis(IM)from primary HCC(PHCC);2)multicentric occurrence(MO)from a newborn tumor.Clinically,RHCC with different origins have conspicuous different treatments and prognosis.Early diagnosis of the RHCC origin contribute to choice of treatments and improve prognosis.In this study,I first reported a case of de winter syndrome with bifurcation lesion.I then tested the utility of a modified jailed-balloon technique(M-JBT)for the long-term treatment effect of de winter syndrome.Meanwhile,this study applies whole exon sequencing(WES)data from samples of primary and recurrent tumors of nine HCC patients,to screen for mutations associated with the origin types of RHCC.Methods 1.A patient with acute chest pain was recorded with ECG pattern and treated with M-JBT percutaneous coronary intervention(PCI).Coronary angiography(CAG)was performed after operation,2 months and 8 months after operation.2.32 samples of PHCC 、 RHCC and normal tissues from 9 HCC patients were underwent WES.SNV distribution of coding region,known driver genes,mutation spectrum,mutation signature,and phylogenetic analysis,were performed to IM/MO diagnosis.Chi-square test(bilateral test,P<0.05)was applied to examine the significant differences in mutation spectrum ratios across samples.Results 1.There was no side branch(SB)injury during PCI with M-JBT,and the ECG pattern of de Winter syndrome disappeared after treatment.Blood flow of the main branch(MB)and SB of the coronary arteries recovered to TIMI level 3 at 2 and 8 months after PCI operation,respectively.2.The data of HCC were analyzed by the filtered(A)and unfiltered paracancer datasets(B).In A,B datasets,there was no shared SNV in primary and recurrent tumors of patient P7,but had shared SNV mutations in other patients.3.There was no shared driving gene between primary and recurrent tumors of patient P7(datasets A,B).In datasets A,the common SNVs between primary and recurrent tumors in patients P1 were located on TMEM170 A,the common SNVs between primary and recurrent tumors in other patients were not located in driver genes.In datasets B,the common SNV between primary and recurrent tumors in patients P1,P3,P5,P8 and P9 were located in driver gene GXYLT1(P1),TMEM170A(P1),MUC17(P3),LRP1B(P5),PI3KCA(P5),USP25(P8)and DSE(P9),the common SNV between primary and recurrent tumors in patients P2,P4,P6 were not located in driver genes.4.The mutation spectrum significantly differed(P=0.0005)between primary and recurrent tumor of patient P7,no significantly difference were found in patients P1,P2,P3,P5,P6,P7,P8 and P9(datasets A,B).For patient P4,mutation spectrum was no significant difference between primary and recurrent tumor in datasets A,but there was significant difference in dataset B(P = 0.044).For patient P7,there was no shared mutation signatures between primary and recurrent tumor in datasets A,but had shared mutation signatures 1 and 3 in datasets B.For other patients,primary and recurrent tumor at least shared mutation signature 3(datasets A,B).5.In datasets A,phylogenetic analysis showed that the primary and recurrent tumors of patient P4 were not clustered together,while the primary and recurrent tumors of other patients were clustered together.In datasets B,the primary and recurrent tumors of patients P2,P4 were not clustered together,while the primary and recurrent tumors of other patients were clustered together.Conclusion 1.We recommend early detection of characteristic ECG in patients with chest pain can prevent de winter syndrome and using M-JBT during PCI stenting for patients with de Winter syndrome and bifurcation lesions,which technique is safe and effective.2.WES analysis showed that the recurrent tumors of patients P2,P4 and P7 belong to MO,the recurrent tumors of other patients belong to the IM.