To investigate the exact age-adjusted incidence (AAI), clinical characteristics, and survival data of collecting duct carcinoma of the kidney (CDCK) recorded in the Surveillance, Epidemiology, and ...End Results (SEER) database of the National Cancer Institute.
Patients with CDCK confirmed by microscopic examination from 2004 to 2018 were selected from the SEER database. AAI rates were calculated using SEER*Stat software (version 8.3.9). The Kaplan-Meier method was used to evaluate cancer-specific survival (CSS) rates according to tumor size, tumor stage, and treatment methods, and differences among these variables were assessed by the log-rank test. Cox regression analysis was employed to identify variables independently related to CSS.
A total of 286 patients with CDCK were identified from the database. The majority of the patients were white (69.2%), male (67.5%), and married (60.5%), and the median age was 59 years. Most patients with CDCK (74.4%) presented with stages III or IV disease. The diameter of most (59.4%) tumors was less than 7 cm, and the tumors were more commonly found on the left than on the right (55.2%
44.8%). The incidence of CDCK decreased over time. The median CSS time was 17 months. In terms of the treatment modalities used, 83.9% of the patients underwent surgery; 32.9% underwent chemotherapy, and 13.6% underwent radiotherapy. The CSS rates at 1, 2, and 5 years were 57.3%, 43.2%, and 30.7%, respectively. In patients with stage IV CDCK treated with surgery alone, chemotherapy alone, and surgery plus chemotherapy, the median survival time was 5 months, 9 months, and 14 months, respectively (
=0.024). Multivariate Cox regression analysis showed surgery, chemotherapy, stage, regional lymph node metastasis, and distant metastasis were independent prognostic factors for patients with CDCK.
CDCK is an uncommon malignant renal carcinoma, and its incidence is decreasing based on the analysis of current data. CDCK is a high stage, regional lymph-nodes positive, and metastatic disease. Compared with surgery alone or chemotherapy alone, patients with stage IV could gain survival benefit from surgery combined with chemotherapy.
This study aims to determine the prognostic value of SII for non-metastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). We retrospectively collected and ...analyzed 328 non-metastatic ccRCC patients with VTT who underwent radical nephrectomy and thrombectomy from 3 tertiary centers in China between 2011 to 2021. Kaplan-Meier analyses and Cox proportional hazard analyses were used to determine its prognostic value for overall survival (OS) and disease free survival (DFS). The Harrell concordance index (C-index), receiver operating characteristic curve (ROC) analysis, and decision curve analysis (DCA) were used to evaluate its role in the improvement of prognostic accuracy of the existing models. Nomogram models containing the SII were then developed and evaluated by R. Patients were divided into low-SII and high-SII groups based on the SII optimal cut-off value 912 calculated by the Youden index in all patients. Higher SII was correlated with more symptoms, longer surgical time, higher WHO/ISUP grade, and longer tumor diameter. Kaplan-Meier analyses revealed significant differences in OS and DFS between two groups. Multivariate analyses revealed that SII was an independent prognostic factor for OS (HR:2.220, p=0.002) and DFS (HR:1.846, p=0.002). Compared with other indicators, SII had a superior accuracy (c-index=0.630 for OS and 0.595 for DFS). It also improved the performance of models for predicting OS and DFS (all p <0.01). Based on the results of LASSO Cox regression analysis, we constructed a nomogram to predict OS and it performed well on both the training cohort (AUC=0.805) and the validation cohort (AUC=0.795). Risk stratification based on nomogram can distinguish patients with different risks (all p <0.001). Preoperative SII is an independent predictive factor for OS and DFS of non-metastatic ccRCC patients with VTT. It can be used to improve the performance of current risk models.
Background
This study aimed to identify disease‐causing variants within a Chinese family affected by Birt–Hogg–Dubé syndrome (BHDS), which arises from an autosomal dominant inheritance pattern ...attributed to variants in the folliculin (FLCN) gene, recognized as a tumor suppressor gene.
Methods
A Chinese proband diagnosed with BHDS due to renal tumors underwent next‐generation sequencing (NGS), revealing a novel variant in the FLCN gene. Sanger sequencing was subsequently performed on blood samples obtained from family members to confirm the presence of this variant.
Results
A novel germline frameshift variant (NM_144997.5:c.977dup) was identified in five individuals among the screened family members, marking the first report of this variant. Additionally, a somatic frameshift variant (NM_144997.5:c.1252del) was detected in the renal tumors of the proband. No variant was detected in unaffected family members.
Conclusions
A novel heterozygous variant was identified in exon 9 of the FLCN gene, which broadens the spectrum of FLCN variants. We recommend that molecular analysis of the FLCN gene be performed in patients with suspected BHDS and their families.
In a BHD‐associated renal tumors Chinese family. A novel heterozygous variant (NM_144997.5:c.977dup) was identified in exon 9 of the FLCN gene, which broadens the spectrum of FLCN variants. We recommend that molecular analysis of the FLCN gene be performed in patients with suspected BHDS and their families.
Progress in the diagnosis and treatment of clear cell renal cell carcinoma (ccRCC) has significantly prolonged patient survival. However, ccRCC displays an extreme heterogenous characteristic and ...metastatic tendency, which limit the benefit of targeted or immune therapy. Thus, identifying novel biomarkers and therapeutic targets for ccRCC is of great importance.
Pan cancer datasets, including the expression profile, DNA methylation, copy number variation, and single nucleic variation, were introduced to decode the aberrance of copper death regulators (CDRs). Then, FDX1 was systematically analyzed in ccRCC to evaluate its impact on clinical characteristics, prognosis, biological function, immune infiltration, and therapy response. Finally, in vivo experiments were utilized to decipher FDX1 in ccRCC malignancy and its role in tumor immunity.
Copper death regulators were identified at the pancancer level, especially in ccRCC. FDX1 played a protective role in ccRCC, and its expression level was significantly decreased in tumor tissues, which might be regulated via CNV events. At the molecular mechanism level, FDX1 positively regulated fatty acid metabolism and oxidative phosphorylation. In addition, FDX1 overexpression restrained ccRCC cell line malignancy and enhanced tumor immunity by increasing the secretion levels of IL2 and TNFγ.
Our research illustrated the role of FDX1 in ccRCC patients' clinical outcomes and its impact on tumor immunity, which could be treated as a promising target for ccRCC patients.
RNA methylation plays a key role across biological processes, which could be utilized as new weapons for cancer management. However, the implication of RNA methylation regulators in cancers, ...especially in clear cell renal cell cancer (ccRCC), remains largely unknown. We investigated the multiomics profile of RNA methylation regulators at the pan‐cancer level. We found most RNA methylation regulators were dysregulated in cancers, which might be explained by genomic mutation and copy number variation. A novel subtype of ccRCC, RNA modification cancer subtype 2 (RMCS2), was identified and verified among different ccRCC cohorts. RMCS2 led to a shortened overall survival and had an activated state of PI3K‐AKT‐mTOR, KRAS, and retinoic acid metabolism signals, which resulted in an immune exhausted phenotype. In summary, our findings demonstrated that the aberrance of RNA methylation regulators was a common biological phenomenon pan‐cancer. Dysregulated RNA methylation patterns could reshape tumor immunity thus impacting patients' prognosis and therapeutic response, and could function as a promising tool for ccRCC patients.
Based on a pan RNA modification profile of clear cell renal cell carcinoma (ccRCC) and machine learning, we identified and verified two novel subtypes of ccRCC, which had distinctive prognoses, multiomics landscapes, and management strategies. Among these, EIF4A1 and HNRNPA2B1 could be treated as novel diagnostic and therapeutic biomarkers in ccRCC.
e16520 Background: Venous tumor thrombus (VTT) is observed in 4−10% of newly diagnosed RCC patients, and a successful radical nephrectomy and thrombectomy provides considerable palliation to a ...proportion of nonmetastatic RCC patients with VTT. However, the reported postsurgical survival varies significantly with the 5‐year overall survival (OS) rate ranging from 37.0 to 71.0%. Hence, accurate risk factors are critically needed for these patients. Here we evaluate the prognostic significance of VTT grading for these patients. Methods: The final evaluable dataset enrolled 706 consecutively nonmetastatic ccRCC patients who underwent radical nephrectomy and thrombectomy, including 304 in the Training cohort from the Eastern China Renal Cancer Collaborative Group, 320 in the China‐Validation cohort and 82 in the Poland‐Validation cohort. All pathological specimens were centrally reviewed by three genitourinary pathologists blinded to clinical information. Univariable and multivariable Cox regression analyses were performed to identify independent predictors associated with survival outcomes. Results: To comprehensively evaluate the potential of VTT in risk assessment, multiple characteristics of VTT were incorporated, including VTT height, consistency and the pathological nuclear grading of VTT (VTT grading), which has not been studied yet. Although higher pathological grading of primary tumor (PT) and VTT were both significantly correlated with dismal prognosis, only VTT grading remained as an independent predictive factor for OS and DFS after multivariable Cox regression. Furthermore, VTT grading showed superiority in risk assessment compared with PT grading and other variables by c‐index analysis (OS: 0.663 vs. 0.501–0.610, 0.667 vs. 0.544–0.651, and 0.719 vs. 0.511–0.700 for Training, China‐Validation, and Poland‐Validation cohorts, respectively; DFS: 0.664 vs. 0.501–0.606, and 0.672 vs. 0.530–0.640 for Training, and China‐Validation cohorts, respectively), which was confirmed by the receiver operating characteristic (ROC) analysis (OS: area under the curve AUC 0.764 vs. 0.650–0.664, 0.684 vs. 0.650–0.667, and 0.814 vs. 0.641–0.711 for Training, China‐Validation, and Poland‐Validation cohorts, respectively; DFS: AUC 0.753 vs. 0.648–0.651, and 0.704 vs. 0.601–0.665 for Training, and China‐Validation cohorts, respectively). Conclusions: VTT grading displayed superior accuracy and discriminatory ability in predicting survival risk for nonmetastatic ccRCC patients with VTT. Assessing VTT grading in routine pathology reports may provide further information for stratification of patient risk.
Background
Dysregulation of Long Non-coding RNAs (lncRNAs) emerges to be a hallmark of cancers. Metastatic prostate cancer and localized disease that recurs after treatment are clinical challenges, ...it remains unclear how lncRNA plays a role in those processes.
Methods
From previous RNA-Seq data on 65 prostate cancer and adjacent normal tissues. We identified a novel lncRNA ENST00000503625 down-regulated in prostate cancer and correlated with tumor progression characteristics. Public datasets were examined for associations between ENST00000503625 expression and clinical parameters and prognoses. Subsequently, we constructed and externally validated a nomogram for predicting biochemical recurrence (BCR). Finally, in vitro experiments were carried out to determine how ENST00000503625 functions biologically in prostate cancer.
Results
Low ENST00000503625 in tumor was associated with poor clinical features and prognoses. TCGA pan-cancer analysis found that ENST00000503625 was deregulated in a variety of tumors and correlated with overall survival, disease-specific survival, and progression-free survival. The nomogram for predicting BCR was constructed using TCGA data, which exhibited excellent accuracy in external validation with Chinese Prostate Cancer Genome and Epigenome Atlas data. Gene Ontology and KEGG pathway analysis found that genes related to ENST00000503625 were enriched in multiple tumor progression related pathways. When ENST00000503625 was knocked down in vitro, the epithelial-mesenchymal transition was induced, by which cancer cells migrated and invaded more readily.
Conclusion
Our data suggested that ENST00000503625 may serve as a potential prognostic marker or a therapeutic target for prostate cancer metastases.
There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole‐exome ...sequencing on normal‐tumor‐thrombus‐metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C‐index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501–0.610, 0.667 versus 0.544–0.651, and 0.719 versus 0.511–0.700 for Training, China‐Validation, and Poland‐Validation cohorts, respectively). We constructed a risk predicting model, TT‐GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT‐GPS score displayed better discriminatory ability (OS, c‐index: 0.706–0.840, AUC: 0.788–0.874; DFS, c‐index: 0.691–0.717, AUC: 0.771–0.789) than previously reported models in risk assessment. In conclusion, we identified for the first‐time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT‐GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.
Inspired by the metastasis‐seeding potential of VTT in ccRCC, we identified for the first time that pathological grading of VTT could serve as an unheeded prognostic factor. By incorporating VTT grading, TT‐GPS score was constructed, displaying superior discriminatory ability for risk stratification in nonmetastatic ccRCC patients with VTT. This study highlights the significance of introducing VTT grading or TT‐GPS score into routine pathological reports to improve the efficacy of risk assessment.
Sunitinib is widely used as a first-line treatment for advanced renal cell carcinoma (RCC). However, a number of patients with RCC who receive sunitinib develop drug resistance; and the biological ...mechanisms involved in resistance to sunitinib remain unclear. It has previously been suggested that the protein glutaminyl-peptide cyclotransferase (QPCT) is closely related to sunitinib resistance in RCC. Thus, in the present study, in order to further examine the molecular mechanisms responsible for sunitinib resistance in RCC, sunitinib-non-responsive and -responsive RCC tissue and plasma samples were collected and additional experiments were performed in order to elucidate the molecular mechanisms responsible for sunitinib resistance in RCC. The upstream and downstream regulatory mechanisms of QPCT were also evaluated. On the whole, the data from the present study suggest that QPCT, CCCTC-binding factor (CTCF) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) may be used as targets for predicting, reversing and treating sunitinib-resistant RCC.
Adoptive cell therapy (ACT) is a promising treatment that is considered safe and efficient. Natural killer (NK) cells play an important role in the innate immune system and destroy target cells such ...as tumor cells without prior sensitization. Here, we report a 59-year-old man with advanced diffuse hepatocellular carcinoma (HCC) who underwent 17 courses of NK cell treatment from March 2017 to July 2018. Although he presented with progressive disease, his hydrothorax and ascites decreased, and his state of mind, appetite and quality of life were markedly improved after treatment versus at admission. To date, his survival time is >48 months. Here, we provide evidence that NK cell adoptive therapy has no adverse effects, enhances immune function, and improves the quality of life of patients with HCC.
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