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Abstract Objectives The pathological mechanisms of patients with Renal Cell Carcinoma (RCC) remain defined. This study aimed to evaluate relationships between the landscape of gene mutations and their clinical significance in RCC patients. Methods Tissue and peripheral blood samples of 42 patients with RCC were collected and performed for the Next Generation Sequencing (NGS) with Geneseeq PrimeTM 425-gene panel probes. Their landscapes of gene mutation were analyzed. We also carried out an evaluation of Tumor-Node-Metastasis (TNM) staging, RENAL nephelometry score, surgery, and targeted drug treatment of patients. Then we compared the correlations of landscape in gene mutations and the prognosis. Results The most common gene alternations, including BAP1, PBRM1, SETD2, CSF1R, NPM1, EGFR, POLE, RB1, and VHL genes, were identified in tissue and blood samples of 75% of patients. EGFR, POLE, and RB1 gene mutations frequently occurred in relapsed and metastatic patients. BAP1, CCND2, KRAS, PTPN11, ERBB2/3, JAK2, and POLE were presented in the patients with > 9 RENAL nephelometry score. Univariable analysis indicated that SETD2, BAP1, and PBRM1 genes were key factors for Disease-Free Survival (DFS). Multivariable analysis confirmed that mutated SETD1, NPM1, and CSF1R were critical factors for the Progression Free Survival (PFS) of RCC patients with target therapy. Conclusions Wild-type PBRM1 and mutated BAP1 in patients with RCC were strongly associated with the outcomes of the patient. The PFS of the patients with SETD2, NPM1, and CSF1R mutations were significantly shorter than those patients without variants.
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@#Abstract: Objective To analyze the association between drug resistance and the risk of latent tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis, and to explore whether the compensatory mutation of drug-resistant Mycobacterium tuberculosis will enhance its pathogenicity or transmission ability. Methods The English and Chinese databases, including PubMed, web of science, EMBASE, Cochrane library database, CNKI and Wanfang database, were searched by computer from the time of establishment of the database to January 2022. Cohort studies on the risk of infection and disease among household contacts of patients with drug-resistant and sensitive pulmonary tuberculosis were searched and screened according to the inclusion and exclusion criteria. The data were extracted and evaluated by NOS scale, using stata16.0 software meta-analysis to calculate the combined effect of tuberculosis infection and disease risk of family contacts, and carry out heterogeneity test, subgroup analysis and sensitivity analysis. Results A total of 7 cohort studies involving 9653 TB index cases and 29, 734 house contacts were included. The results of meta-analysis showed that compared with drug-sensitive pulmonary tuberculosis patients, the risk of tuberculosis infection in house contacts of drug-resistant pulmonary tuberculosis patients was increased (OR=1.56, 95%CI=1.25-1.96, P<0.001), but there was no difference in the risk of incidence (RR=1.06, 95%CI=0.80-1.41, P=0.67>0.05). Subgroup analysis showed that the risk of latent tuberculosis infection in house contacts was affected by the study area, and the size of family contacts had an impact on the risk of TB . Sensitivity analysis showed that the results of meta-analysis were robust. Conclusion Compared with drug sensitive TB patients, household contacts with drug-resistant TB patients had a higher risk of tuberculosis, but there was no difference in the risk of TB among the two groups.