Role of N6-methyladenine regulators in prognosis and immune infiltration of cervical cancer / 中国免疫学杂志

Objective:To explore potential role and mechanism of N6-methyladenine(m6A)RNA methylation regulators in prognosis and tumor immune microenvironment of cervical cancer.Methods:Clinical and survival data as well as RNA sequencing data were acquired from TCGA and GEO database.Expressions and correlation among m6A RNA methylation regulators were analyzed by bioinformatics analysis and tissue validation experiments.LASSO Cox regression analysis was used to generate a prognostic risk sig-nature based on m6A regulators.Two m6A-modification patterns were identified based on m6A regulators and their abundance of im-mune cell inflitration were analyzed by ssGSEA.Results:Compared with normal tissues,RBM15,IGF2BP2,IGF2BP3,FMR1,YTHDF1,METTL3 and YTHDF2 expressions were significantly up-regulated in cervical cancer tissues,while ZC3H13,METTL4,YTHDC1,FTO and ALKBH3 expressions were significantly down-regulated.Five m6A regulators HNRNPC,LRPPRC,METTL3,ELAVL1 and FMR1 were selected to establish prognostic risk signature,whose expressions in cervical cancer were verified by HPA database and qRT-PCR with good predictive value,and could be used as independent poor prognostic factor(AUC=0.734).Based on expressions of 25 m6A regulators,two m6A modification patterns m6Acluster A and m6Acluster B were determined.There were differ-ences between two groups in biological functions,signal pathways and immune cells infiltration levels in tumor microenvironment.Conclusion:m6A RNA methylation regulators are closely related to prognosis and immune infiltration of cervical cancer,which provides guidance for immunotherapy strategy.

Analysis of phenotype and FH gene variation in a pedigree affected with hereditary leiomyomatosis and renal cell carcinoma syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze clinical phenotype and genetic variants in a Chinese pedigree of hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome.@*METHODS@#Whole exome sequencing was carried out for the proband from the pedigree. Suspected FH gene variants were validated by Sanger sequencing. Clinical manifestation and histopathological examination were used to analyze the pedigree comprehensively.@*RESULTS@#The pedigree met the clinical diagnostic criteria for HLRCC syndrome. The whole exome sequencing showed that the FH gene of the proband had a heterozygous missense variant of c.1490T>C (p.F497S), which was consistent with the Sanger sequencing. The mother, daughter and son of the proband all had the heterozygous missense variant of c.1490T>C (p.F497S). According to the American Society of Medical Genetics and Genomics Classification Standards and Guidelines for Genetic Variations, c.1490T>C (p.F497S) (PM2+PP1-M+PP3+PP4) was a possible pathogenic variant. Based on our literature search, this variant was a new variant that had not been reported.@*CONCLUSION@#The FH gene missense variant of c.1490T>C (p.F497S) may be the cause of the HLRCC syndrome pedigree, which provides a basis for the genetic diagnosis and genetic counseling of the HLRCC syndrome.

Clinical features and management of primary malignant renal perivascular epithelioid cell tumor / 中华泌尿外科杂志

Objective To summary the pathological and clinical characteristics,treatments and prognosis of malignant renal perivascular epithelioid cell tumor (PEComa).Methods Between August 2013 and June 2017,8 cases of malignant renal PEComa were analysed respectively.Of all the patients,there were 4 males and 4 females,aged 27-65 years with the average of 46.3 years old.Three cases were detected in routine examination occasionally,three cases complained of intermittent back pain with fever,one presented with swollen and painful right hand and right foot,and one case presented with hematuria.CT or MRI examinations indicated the malignant lesions before the surgery.Clinical staging was performed with 2 cases of T1N0M0,1 case of T1 N0M1,2 cases of T2N0M0,1 case of T3M0M0,and 2 cases of T4N0M1.Three cases underwent radical nephrectomy,1 case underwent radical nephrectomy plus renal artery embolization,2 cases underwent partial nephrectomy,and 2 cases underwent nephrectomy plus inferior vena cava tumor thrombectomy.One case was treated with ifosfamide plus epirubicin after operation due to multiple distant metastases and 1 case was treated with oxaliplatin before the sugery because of excessive tumor diameter.None of the rest received any adjuvant therapy.Results Postoperative histopathological examination showed multiple nodules in reddish gray and yellow color,with soft texture and partial incomplete capsule.Microscopically,there were large atypical cell components,some of which were spindle shaped,with disordered cell arrangement,some of which were associated with a large amount of necrotic tissue,and abundant light eosinophil cytoplasm.Tissue components can be found thick-wall blood vessels,smooth muscle-like cells,and adipose tissue.Immunohistochemistry showed 4 cases were positive of HMB-45,4 of Melan-A,7 of SAM.Seven cases were negative of CK,6 of S-100 75％ (6/8) and Ki67 (10％-70％).Two cases died of multiple metastases (lung,bone,liver),1 case survived with tumor recurrence,with a follow-up from 14 to 60 months (mean 29 months).Conclusions Primary malignant renal PEComa is rare in practice with relative large diameter.The diagnosis depends on pathological findings,and radical nephrectomy is the first choice of treatment.It is easy to recur and metastasize after the operation.

Schwannoma of the kidney: report of two cases and review of the literature / 中华泌尿外科杂志

Objective To discuss the pathological and clinical characteristics,treatments and prognosis of schwannoma of the kidney.Methods Two cases of schwannoma of the kidney in our hospital were reviewed with clinicopathological data and their follow-up.The related literatures were reviewed.The first case was a male patient,28 years old,complained about paroxysmal abdominal pain with nausea over 2 weeks.The physical exam found a 10 cm,qualitative hard,poor activity,tenderness mass in kidney region.MRI preoperative diagnosis was right renal cell carcinoma with renal vein and inferior vena cava tumor thrombus formation.The second patient,female,53 years old,the mass on upper right kidney was found occasionally.It was diagnosed as adrenal pheochromocytoma before operation,laparoscopic resection of right renal hilum mass and right partial adrenectomy plus right nephrectomy were performed.There was no tumor recurrence in the follow-up.Results The abdominal aortography and double renal arteriography were done and right renal artery embolization and inferior vena cava filter were allocated.Then right radical nephrectomy and inferior vena cava tumor thrombus removal were carried out on the first patient.The first malignant and the second benign renal schwannoma patient showed significant difference in pathological presentations.Their immunohistochemistry also showed great diversity.Malignant renal schwannoma was significantly stained by Ki-67 ＞ 40％,S-100 was negative.Ki-67 in benign neurilemmomas was about 2％,and S-100 in benign renal schwannoma was positive.Conclusions Schwannoma of the kidney is rare with a favorable prognosis.The golden standard of diagnosis is pathology.Surgical resection has become the first choice for treatment.Recurrence and malignant transformation would happen after the surgery so that all the patients should be followed up.