SUMMARY Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival.
Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features.
Since December 2019, an increasing number of cases of the 2019 novel coronavirus disease (COVID-19) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified in Wuhan, Hubei Province, China. Now, more cases have been reported in 200 other countries and regions. The pandemic disease not only affects physical health who suffered it, but also affects the mental health of the general population. This study aims to know about the impact of the COVID-19 epidemic on the health-related quality of life (HRQOL) of living using EQ-5D in general population in China. Methods An online-based survey was developed and participants were recruited via social media. The questionnaires included demographic and socioeconomic data, health status, the condition epidemic situation and EQ-5D scale. The relationships of all factors and the scores of EQ-5D were analyzed. Logistic regression model were used to the five health dimensions. Results The respondents obtained a mean EQ-5D index score of 0.949 and a mean VAS score of 85.52.The most frequently reported problem were pain/discomfort (19.0%) and anxiety/ depression (17.6%). Logistic regression models showed that the risk of pain/discomfort and anxiety/depression among people with aging, with chronic disease, lower income, epidemic effects, worry about get COVID-19 raised significantly. Conclusion The article provides important evidence on HRQOL during the COVID-19 pandemic. The risk of pain/discomfort and anxiety/depression in general population in China raised significantly with aging, with chronic disease, lower income, epidemic effects, worried about get
Elevated NLR is a predictor of shorter survival in patients with advanced PC.
Importance Although patients with resected pancreatic adenocarcinoma are at high risk for disease recurrence, few markers are available to inform patient outcomes. Objective To evaluate alterations of the four main driver genes for pancreatic adenocarcinoma and patient outcomes after cancer resection. Design, Setting, and Participants We analyzed protein expression and DNA alterations for KRAS, CDKN2A, SMAD4, and TP53 by immunohistochemistry and next-generation sequencing in formalin-fixed, paraffin-embedded tumors from 356 patients with resected pancreatic adenocarcinoma evaluated at three U.S. centers. Associations of driver gene alterations with disease-free survival (DFS) and overall survival (OS) were evaluated using Cox proportional hazards regression with estimation of hazard ratios (HR) and 95% confidence intervals (CI) and adjustment for age, sex, tumor characteristics, institution, and peri-operative treatment. Main Outcomes DFS and OS among patients with resected pancreatic adenocarcinoma Results Patients with KRAS mutant tumors had worse DFS and OS compared to patients with KRAS wild-type tumors, with median OS of 20.3 versus 38.6 months and 5-year OS of 13.0% versus 30.2%, respectively. Particularly poor outcomes were identified in patients with KRAS G12D-mutant tumors, who had median OS of 15.3 months. Patients whose tumors lacked CDKN2A expression had worse DFS and OS compared to patients whose tumors retained CDKN2A, with median OS of 19.7 versus 24.6 months and 5-year OS of 11.9% versus 19.5%, respectively. SMAD4 status was not associated with DFS or OS, while TP53 status was associated only with DFS (P=0.04). Patients had worse DFS and OS with greater number of altered driver genes. Compared to patients with 0-2 altered genes, those with 4 altered genes had HR for DFS of 1.79 (1.24-2.59; P<0.01) and OS of 1.38 (0.98-1.94; P=0.06). Five-year OS was 18.4% for patients with 0-2 gene alterations, 14.1% for 3 alterations and 8.2% for 4 alterations. Alterations in the four driver genes were not significantly associated with local recurrence as the first site of disease recurrence. Conclusions and Relevance Patient outcomes are associated with alterations of the four main driver genes in resected pancreatic adenocarcinoma.
BACKGROUND.The authors investigated the prevalence of hepatitis B virus (HBV) infection by using serologic markers in non‐Hodgkin lymphoma (NHL) compared with other types of cancers in Chinese patients.METHODS.In this case‐control study, HBV and other hepatitis markers were compared between a study group and a control group. The study group included 587 patients with NHL (age range, 16–86 years), and the control group included 1237 patients (age range, 16–89 years) who were diagnosed with other cancers except liver cancer. An enzyme‐linked immunosorbent assay was used to test serum samples from both groups for HBV markers and other hepatitis markers.RESULTS.Logistic regression analysis showed that there was a higher prevalence of HBV infection in patients with the B‐cell subtype of NHL (30.2%) than in patients with other cancers (14.8%; odds ratio [OR], 2.6; 95% confidence interval [95% CI], 2.0–3.4); however, in patients with the T‐cell subtype of NHL, the HBV infection rate (19.8%) was similar to that among patients with other cancers (OR, 1.2; 95% CI, 0.8–1.8). A significant difference in HBV prevalence was found between B‐cell and T‐cell NHL (OR, 2.3; 95% CI, 1.4–3.6). In the patients with B‐cell NHL, those who were infected with HBV had a significantly earlier disease onset (9.5 years) than those who were not infected with HBV.CONCLUSIONS.The current results demonstrated that patients with B‐cell NHL, but not patients with T‐cell NHL, had a higher prevalence of HBV infection. HBV infection was associated with a significantly earlier disease onset (P < .001), a finding that suggested the possibility that HBV may play an etiologic role in the induction of B‐cell NHL. Cancer 2007. © 2007 American Cancer Society.
Breast cancer is the most common malignancy for women. Multiple oncogenes, tumor suppressor genes, sex steroid hormones and their receptors are involved in the genesis and development of breast cancer. Breast cancer is also a heterogeneous tumor including a variety of subtypes with different biological behaviors, clinicopathologic features and molecular characteristics. The responses to treatment and the prognosis of different subtypes of breast cancer are also markedly different. Triple negative breast cancer (TNBC) is a newly proposed subtype of breast cancer, with poor biological behaviors, high invasiveness and poor prognosis. It can not benefit from endocrine therapy and HER2targeted therapy due to the negative estrogen receptor (ER), negative progesterone receptor (PR) and negative human epidermal growth factor receptor2 (HER2) [1] . Therefore, TNBC is mainly treated by chemotherapy. Currently, the clinical study for TNBC mainly focuses on prognostic indicators and the selection of therapeutic drugs. In recent years, it has been showed that androgen and androgen receptor (AR) also play an important role in the genesis and development of breast cancer, but their effects in different subtypes of breast cancer are still unclear. In the present study, we investigated the expression of AR in TNBC, and explored its correlation with the clinicopathologic features and prognosis of TNBC.
T cells specific for nucleosomal autoepitopes are selectively expanded in lupus mice and these Th cells drive autoimmune B cells to produce pathogenic antinuclear antibodies. We transfected the TCR-α and -β chain genes of a representative, pathogenic autoantibody-inducing Th clone specific for the nucleosomal core histone peptide H471–94 into TCR-negative recipient cells. Although the autoimmune TCRs were originally derived from SNF1 (I-Ad/q) mice, the transfectants could recognize the nucleosomal autoepitope presented by APC-bearing I-A molecules of all haplotypes tested, as well as human DR molecules. Competition assays indicated that the autoepitopes bound to the MHC class II groove. Most remarkably, MHC-unrestricted recognition of the nucleosomal peptide epitope was conferred by the lupus TCR-α chain even when it paired with a TCR-β chain of irrelevant specificity. Several other disease-relevant Th clones and splenic T cells of lupus mice had similar properties. The TCR-α chains of these murine lupus Th clones shared related motifs and charged residues in their CDRs, and similar motifs were apparent even in TCR-α chains of human lupus Th clones. The lupus TCR-α chains probably contact the nucleosomal peptide complexed with MHC with relatively high affinity/avidity to sustain TCR signaling, because CD4 coreceptor was not required for promiscuous recognition. Indeed, pathogenic autoantibody-inducing, CD4-negative, TCR-αβ+ Th cells are expanded in systemic lupus erythematosus. These results have implications regarding thymic selection and peripheral expansion of nucleosome-specific T cells in lupus. They also suggest that universally tolerogenic epitopes could be designed for therapy of lupus patients with diverse HLA alleles. We propose to designate nucleosomes and other antigens bearing universal epitopes “Pantigens” (for promiscuous antigens).
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