Comprehensive analysis of lncRNAs as biomarkers for diagnosis, prognosis, and treatment response in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common histological type of renal carcinoma and has a high recurrence rate and poor outcome. Accurate patient risk stratification based on genetic markers can help to identify the high-risk patient for early and further treatments and would promote patient survival. Long non-coding RNAs (lncRNAs) have attracted widespread attention as biomarkers for early diagnosis, treatment, and prognosis because of their high specificity and sensitivity. Here, we performed a systematic search in NCBI PubMed and found 44 lncRNAs as oncogenes, 18 lncRNAs as tumor suppressors, 199 lncRNAs as diagnostic biomarkers, 62 lncRNAs as prognostic biomarkers, and 3 lncRNAs as predictive biomarkers for ccRCC. We also comprehensively discuss the biological functions and molecular regulatory mechanisms of lncRNAs in ccRCC. Overall, the present study is a systemic analysis to assess the expression and clinical value of lncRNAs in ccRCC, and lncRNAs hold promise to be diagnostic, prognostic, and predictive biomarkers.

Diffuse interstitial pneumonia-like/macrophage activation syndrome-like changes in patients with COVID-19 correlate with length of illness.

OBJECTIVES: Assess the pathologic changes in the lungs of COVID-19 decedents and correlate these changes with demographic data, clinical course, therapies, and duration of illness. METHODS: Lungs of 12 consecutive COVID-19 decedents consented for autopsy were evaluated for gross and histopathologic abnormalities. A complete Ghon "en block" dissection was performed on all cases; lung weights and gross characteristics recorded. Immunohistochemical studies were performed to characterize lymphocytic infiltrates and to assess SARS-CoV-2 capsid protein. RESULTS: Two distinct patterns of pulmonary involvement were identified. Three of 12 cases demonstrated a predominance of acute alveolar damage (DAD) while 9 of 12 cases demonstrated a marked increase in intra-alveolar macrophages in a fashion resembling desquamative interstitial pneumonia or macrophage activation syndrome (DIP/MAS). Two patterns were correlated solely with a statistically significant difference in the duration of illness. The group exhibiting DAD had duration of illness of 5.7 days while the group with DIP/MAS had duration of illness of 21.5 days (t-test p = 0.014). CONCLUSIONS: The pulmonary pathology of COVID-19 patients demonstrates a biphasic pattern, an acute phase demonstrating DAD changes while the patients with a more prolonged course exhibit a different pattern that resembles DIP/MAS-like pattern. The potential mechanisms and clinical significance are discussed.

OSeac: An Online Survival Analysis Tool for Esophageal Adenocarcinoma.

Esophageal Adenocarcinoma (EAC) is one of the most common gastrointestinal tumors in the world. However, molecular prognostic systems are still lacking for EAC. Hence, we developed an Online consensus Survival analysis web server for Esophageal Adenocarcinoma (OSeac), to centralize published gene expression data and clinical follow up data of EAC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). OSeac includes 198 EAC cases with gene expression profiling and relevant clinical long-term follow-up data, and employs the Kaplan Meier (KM) survival plot with hazard ratio (HR) and log rank test to estimate the prognostic potency of genes of interests for EAC patients. Moreover, we have determined the reliability of OSeac by using previously reported prognostic biomarkers such as DKK3, CTO1, and TXNIP. OSeac is free and publicly accessible at http://bioinfo.henu.edu.cn/EAC/EACList.jsp.

Autophagy-related gene P4HB: a novel diagnosis and prognosis marker for kidney renal clear cell carcinoma.

Autophagy can protect cells and organisms from stressors such as nutrient deprivation, and is involved in many pathological processes including human cancer. Therefore, it is necessary to investigate the role of autophagy-related genes (ARGs) in cancer. In this study, we investigated the gene expression of 222 ARGs in 1048 Kidney Renal Clear Cell Carcinoma (KIRC) cases, from 5 independent cohorts. The gene expression of ARGs were first evaluated in the The Cancer Genome Atlas (TCGA) by Recevier Operating Characteristic (ROC) analysis to select potential biomarkers with extremely high ability in KIRC detection (AUC≥0.85 and p<0.0001). Then in silico procedure progressively leads to the selection of two genes in a three rounds of validation performed in four human KIRC-patients datasets including two independent Gene Expression Omnibus (GEO) datasets, Oncomine dataset and Human Protein Atlas dataset. Finally, only P4HB (Prolyl 4-hydroxylase, beta polypeptide) gene was experimentally validated by RT-PCR between control kidney cells and cancer cells. Following univariate and multivariate analyses of TCGA-KIRC clinical data showed that P4HB expression is an independent prognostic indicator of unfavorable overall survival (OS) for KIRC patients. Based on these findings, we proposed that P4HB might be one potential novel KIRC diagnostic and prognostic biomarker at both mRNA and protein levels.

OSuvm: An interactive online consensus survival tool for uveal melanoma prognosis analysis.

Uveal melanoma (UM) is a rare, aggressive, but the most frequent primary intraocular malignancy in adults, and up to 50% of patients develop a tendency of liver metastases. Great efforts have been made to develop biomarkers that facilitate diagnosis, prediction of the risk, and response to treatment of UM. However, a biologically informative and highly accurate gold standard system for prognostic evaluation of UM remains to be established. To facilitate assessment of the prognosis of UM patients, we established a user-friendly Online consensus Survival tool for uveal melanoma, named OSuvm, by which users can easily estimate the prognostic values of genes of interest by the Kaplan-Meier survival plot with hazard ratio and log-rank test. OSuvm comprises four independent cohorts including 229 patients with both gene expression profiles and relevant clinical follow-up information, and it has shown great performance in evaluating the prognostic roles of previously reported biomarkers. Using OSuvm enables researchers and clinicians to rapidly and conveniently explore the prognostic value of genes of interest and develop new potential molecular biomarkers for UM. OSuvm can be accessed at http://bioinfo.henu.edu.cn/UVM/UVMList.jsp.

OSacc: Gene Expression-Based Survival Analysis Web Tool For Adrenocortical Carcinoma.

Gene expression profiling data with long-term clinical follow-up information are great resources to screen, develop, evaluate and validate prognostic biomarkers in translational cancer research. However, an easy-to-use interactive online tool is needed to analyze these profiling and clinical data. In the current work, we developed OSacc (Online consensus Survival analysis of ACC), a web tool that provides rapid and user-friendly survival analysis based on seven independent transcriptomic profiles with long-term clinical follow-up information of 259 ACC patients gathered from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. OSacc allows researchers and clinicians to evaluate the prognostic value of genes of interest by Kaplan-Meier (KM) survival plot with hazard ratio (HR) and log-rank test in ACC. OSacc is freely available at http://bioinfo.henu.edu.cn/ACC/ACCList.jsp.

OSkirc: a web tool for identifying prognostic biomarkers in kidney renal clear cell carcinoma.

Aim: To develop a free and quick analysis online tool that allows users to easily investigate the prognostic potencies of interesting genes in kidney renal clear cell carcinoma (KIRC). Patients & methods: A total of 629 KIRC cases with gene expression profiling data and clinical follow-up information are collected from public Gene Expression Omnibus and The Cancer Genome Atlas databases. Results: One web application called Online consensus Survival analysis for KIRC (OSkirc) that can be used for exploring the prognostic implications of interesting genes in KIRC was constructed. By OSkirc, users could simply input the gene symbol to receive the Kaplan-Meier survival plot with hazard ratio and log-rank p-value. Conclusion: OSkirc is extremely valuable for basic and translational researchers to screen and validate the prognostic potencies of genes for KIRC, publicly accessible at http://bioinfo.henu.edu.cn/KIRC/KIRCList.jsp.

OSgbm: An Online Consensus Survival Analysis Web Server for Glioblastoma.

Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. GBM causes poor clinical outcome and high mortality rate, mainly due to the lack of effective targeted therapy and prognostic biomarkers. Here, we developed a user-friendly Online Survival analysis web server for GlioBlastoMa, abbreviated OSgbm, to assess the prognostic value of candidate genes. Currently, OSgbm contains 684 samples with transcriptome profiles and clinical information from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA). The survival analysis results can be graphically presented by Kaplan-Meier (KM) plot with Hazard ratio (HR) and log-rank p value. As demonstration, the prognostic value of 51 previously reported survival associated biomarkers, such as PROM1 (HR = 2.4120, p = 0.0071) and CXCR4 (HR = 1.5578, p < 0.001), were confirmed in OSgbm. In summary, OSgbm allows users to evaluate and develop prognostic biomarkers of GBM. The web server of OSgbm is available at http://bioinfo.henu.edu.cn/GBM/GBMList.jsp.

S-1 monotherapy versus S-1 combination therapy in gemcitabine-refractory advanced pancreatic cancer: A meta-analysis (PRISMA) of randomized control trials.

BACKGROUND: Pancreatic cancer (PC) is one of the most lethal digestive system tumors. Most new cases are diagnosed based on metastasis or local aggression and are known as "advanced PC." Recently, studies investigating S-1 have indicated that it has a better clinical curative effect on PC. We conducted a meta-analysis to evaluate the efficacy and safety of S-1 monotherapy compared with S-1 combination regimens in patients with gemcitabine (GEM)-refractory PC. METHODS: Trials published between 1978 and 2016 were identified by an electronic search of public databases (Medline, Embase, and the Cochrane Library). All prospective studies were independently identified by 2 authors for inclusion. The response rate (RR), progression-free and overall survival (PFS and OS, respectively), and the primary toxicities were extracted for the meta-analysis. RESULTS: Four randomized controlled trials consisting of 623 patients were included in the analysis, among which 315 patients underwent S-1 monotherapy and 308 patients underwent S-1 combination therapy. The pooled data showed a significantly higher response rate and longer PFS in the S-1 combination group than in the S-1 monotherapy group (RR, 1.75; 95% confidence interval [CI], 1.19-2.57; P = .005 and hazard ration [HR], 0.75; 95% CI, 0.62-0.91; P = .005). There were no significant differences in OS or adverse events. CONCLUSIONS: Compared with the S-1 monotherapy group, the S-1 combination group had a higher response rate and longer PFS. Both groups had few adverse events, which were balanced between the groups. The subgroup analysis suggested that S-1 combination regimens with leucovorin or irinotecan (CPT-11) provided promising efficacy. These promising combination regimens should be considered for patients with advanced PC who choose S-1 as their second-line therapy.

Port-site metastasis as a primary complication following retroperitoneal laparoscopic radical resection of renal pelvis carcinoma or nephron-sparing surgery: A report of three cases and review of the literature.

The present study reports the clinical data of two patients with renal pelvis carcinoma and one patient with renal carcinoma who developed port-site metastasis following retroperitoneal laparoscopic surgery. The current study aimed to identify the cause and prognosis of the occurrence of port-site metastasis subsequent to laparoscopic radical resection of renal pelvis carcinoma and nephron-sparing surgery. Post-operative pathology confirmed the presence of high-grade urothelial cell carcinoma in two patients and Fuhrman grade 3 renal clear cell carcinoma in one patient. Port-site metastasis was initially detected 1-7 months post-surgery. The two patients with renal pelvis carcinoma succumbed to the disease 2 and 4 months following the identification of the port-site metastasis, respectively, whereas the patient with renal carcinoma survived with no disease progression during the targeted therapy period. The occurrence of port-site metastasis may be attributed to systemic and local factors. Measures to reduce the development of this complication include strict compliance with the operating guidelines for tumor surgery, avoidance of air leakage at the port-site, complete removal of the specimen with an impermeable bag, irrigation of the laparoscopic instruments and incisional wound with povidone-iodine when necessary, and enhancement of the body's immunity. Close post-operative follow-up observation for signs of recurrence or metastasis is essential, and systemic chemotherapy may be required in patients with high-grade renal pelvis carcinoma and renal carcinoma in order to prolong life expectancy.