KPNA2 Expression as a Biomarker for Immunosuppressive Microenvironment Predicting Response to TKI and Immunotherapy in Metastatic Renal Cell Carcinoma.

Background: Immunotherapy (IO) combined with tyrosine kinase inhibitors (TKI) are now first-line therapy for advanced renal cell carcinoma (RCC), though reliable predictive biomarkers remain elusive. Recent evidence demonstrates that karyopherin α2 subunit (KPNA2), a nuclear transport regulator, plays key roles in tumorigenesis and therapy resistance.

Methods: Two cohorts were analyzed: an institutional cohort of metastatic RCC patients (ZS-MRCC) and the phase III JAVELIN Renal 101 trial cohort.

Thymidine kinase 1 indicates resistance to immune checkpoint plus tyrosine kinase inhibition in renal cell carcinoma.

Purpose: Immune checkpoint plus tyrosine kinase inhibition (IO + TKI) has emerged as the first-line therapy in metastatic renal cell carcinoma (RCC), but no biomarker can predict its efficacy. Thymidine kinase 1 (TK1) is closely associated with immune evasion in tumors.

Methods: Metastatic RCC patients treated by IO + TKI were enrolled from two cohorts (ZS-MRCC, n = 45; Javelin-101, n = 726).

PSMD2 overexpression as a biomarker for resistance and prognosis in renal cell carcinoma treated with immune checkpoint and tyrosine kinase inhibitors.

Background: Integrated immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) are now the recommended first-line therapy to manage renal cell carcinoma (mRCC). Proteasome 26S subunit non-ATPase 2 (PSMD2) overexpression in tumors has been correlated with tumor progression. Currently, mRCC lacks an established biomarker for the combination of ICI+TKI.

SPP1 expression indicates outcome of immunotherapy plus tyrosine kinase inhibition in advanced renal cell carcinoma.

Clinical guidelines have recently advised combination therapy involving immunotherapy (IO) and tyrosine kinase inhibitors (TKI) as the first-line therapy approach for advanced renal cell carcinoma (RCC). Nevertheless, there is currently no available biomarker that can effectively distinguish the progression-free survival (PFS). RNA-sequencing and immunohistochemistry were conducted on our cohort of metastatic RCC patients, namely ZS-MRCC, who received combination therapy consisting of IO and TKI.

Effect of galectin-1 on prognosis and responsiveness of immune checkpoint plus tyrosine kinase inhibition in renal cell carcinoma.

Background: In renal cell carcinoma (RCC), no clinically available biomarker has been utilized for checkpoint inhibitor immunotherapy (IO) + tyrosine kinase inhibitor (TKI) combinations. Galectin-1 overexpression is found in tumors, with potential immune-regulating roles.

Methods: RNA-sequencing was performed in two cohorts of RCC treated with IO/TKI combination therapy (ZS-MRCC, JAVELIN-101).

Effect of Annexin A2 on prognosis and sensitivity to immune checkpoint plus tyrosine kinase inhibition in metastatic renal cell carcinoma.

Background: Immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) therapy is the first-line recommendation for advanced renal cell carcinoma (RCC), but no biomarker has been approved for it. Annexin A2 (ANXA2) can induce immune escape in tumors.

Methods: Two independent cohorts of advanced RCC treated by IO + TKI were utilized for survival analysis (ZS-MRCC, n = 45; Javelin-101, n = 726).

RUNX3 pathway signature predicts clinical benefits of immune checkpoint inhibition plus tyrosine kinase inhibition in advanced renal cell carcinoma.

Background: Checkpoint inhibitor immunotherapy plus tyrosine kinase inhibitor (IO/TKI) have been recently recommended as standard first-line therapy for advanced renal cell carcinoma, while no clinical-available biomarker has been applied. This study aimed to investigate the associations between RUNX3 pathway signature and IO/TKI benefits in renal cell carcinoma (RCC).

Methods: Two IO/TKI cohorts (ZS-MRCC, JAVELIN-101) and one high-risk localized RCC cohort (ZS-HRRCC) were included.

Effects of PYCR1 on prognosis and immunotherapy plus tyrosine kinase inhibition responsiveness in metastatic renal cell carcinoma patients.

Background: Immunotherapy plus tyrosine kinase inhibitor (IO-TKI) has become the first-line management for metastatic renal cell carcinoma (RCC), despite the absence of biomarkers. Recently, pyrroline-5-carboxylate reductase 1 (PYCR1) and proline metabolism have been reported regulatory roles in the anti-tumor response.

Methods: There were three cohorts enrolled: two from our institution (ZS-MRCC and ZS-HRRCC) and one from a clinical trial (JAVELIN-101).

The prognostic significance of CDK6 expression in renal cell carcinoma treated by immune checkpoint plus tyrosine kinase inhibition.

Checkpoint inhibitor immunotherapy plus tyrosine kinase inhibitor (IO/TKI) has become the first-line treatment for metastatic renal cell carcinoma (RCC), despite the lack of biomarkers. Cyclin-dependent kinase 6 (CDK6) has shown a regulatory role in antitumour response. The study enrolled two cohorts of metastatic RCC treated by IO/TKI (Zhongshan Hospital [ZS]-MRCC, n = 45; JAVELIN-101, n = 726) and two cohorts of localized RCC (ZS-HRRCC, n = 40; TCGA-KIRC, n = 530).

HMOX1 pathway signature predicts clinical benefit from immunotherapy plus tyrosine kinase inhibitor therapy in advanced renal cell carcinoma.

Background: Immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) emerged as standard first-line therapy for advanced renal cell carcinoma (RCC). The heme Oxygenase 1 (HMOX1) pathway is involved in tumor development and treatment resistance, which may affect the efficacy of TKI + IO.

Methods: Two cohorts from our center (ZS-MRCC, ZS-HRRCC), one cohort from clinical trial (JAVELIN Renal 101) and the Cancer Genome Atlas (TCGA-KIRC) were enrolled.

Favorable Immunotherapy Plus Tyrosine Kinase Inhibition Outcome of Renal Cell Carcinoma Patients with Low CDK5 Expression.

Purpose: Immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) has become the first-line treatment for advanced renal cell carcinoma, despite the lack of prognostic biomarkers. Cyclin-dependent kinase 5 (CDK5) affects the tumor microenvironment, which may influence the efficacy of TKI+IO.

Materials And Methods: Two cohorts from our center (Zhongshan Metastatic Renal Cell Carcinoma [ZS-MRCC] cohort, Zhongshan High-risk Localized Renal Cell Carcinoma [ZS-HRRCC] cohort) and one cohort from a clinical trial (JAVELIN-101) were enrolled.

Unfavorable immunotherapy plus tyrosine kinase inhibition outcome of metastatic renal cell carcinoma after radical nephrectomy with increased ADAM9 expression.

Immunotherapy plus tyrosine kinase inhibitor (IO-TKI) has become the standard first-line therapy for advanced renal cell carcinoma (RCC). However, the modest response rate of IO-TKI therapy and the absence of biomarkers limited the selection of treatment strategies for RCC patients. There were three cohorts enrolled: two from our facility (ZS-MRCC and ZS-HRRCC) and one from a clinical study (JAVELIN-101).

Alternative Complement Pathway Signature Determines Immunosuppression and Resistance to Immunotherapy Plus Tyrosine Kinase Inhibitor Combinations in Renal Cell Carcinoma.

Background: Latest guidelines recommended immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) combination as standard first-line therapy in renal cell carcinoma (RCC), with no predictive biomarker being applied. Complement system shapes tumor microenvironment, which may influence TKI+IO benefit.

Methods: Two cohorts from our institute and 2 external cohorts were enrolled.

Exploration of Prognostic Biomarkers of Muscle-Invasive Bladder Cancer (MIBC) by Bioinformatics.

We aimed to discover prognostic factors of muscle-invasive bladder cancer (MIBC) and investigate their relationship with immune therapies. Online data of MIBC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO) database. Weighted gene co-expression network analysis (WGCNA) and univariate Cox analysis were applied to classify genes into different groups.

Identification of Prognostic Biomarkers for Clear Cell Renal Cell Carcinoma (ccRCC) by Transcriptomics.

Objective: Clear cell renal cell carcinoma (ccRCC) is the most common histological type of renal malignancies. Our aim was to find the prognostic crux of ccRCC.

Methods: The data for ccRCC was acquired from The Cancer Genome Atlas (TCGA) and the International Genome Consortium (ICGC) database.

Correction: Up-regulation of p16 by miR-877-3p inhibits proliferation of bladder cancer.

[This corrects the article DOI: 10.18632/oncotarget.10575.

MicroRNA-193a-3p inhibits cell proliferation in prostate cancer by targeting cyclin D1.

MicroRNAs (miRNAs) are small non-coding RNAs that affect various biological processes by altering the expression of a target gene. An miRNA microarray analysis has previously revealed a significant decrease in miR-193a-3p levels in prostate cancer tissues compared with that in their benign prostate hyperplasia counterparts. However, the role of miR-193a-3p has yet to be elucidated.

Age-related Impairment of Vascular Structure and Functions.

Among age-related diseases, cardiovascular and cerebrovascular diseases are major causes of death. Vascular dysfunction is a key characteristic of these diseases wherein age is an independent and essential risk factor. The present work will review morphological alterations of aging vessels in-depth, which includes the discussion of age-related microvessel loss and changes to vasculature involving the capillary basement membrane, intima, media, and adventitia as well as the accompanying vascular dysfunctions arising from these alterations.

Recent Progress in Vascular Aging: Mechanisms and Its Role in Age-related Diseases.

As with many age-related diseases including vascular dysfunction, age is considered an independent and crucial risk factor. Complicated alterations of structure and function in the vasculature are linked with aging hence, understanding the underlying mechanisms of age-induced vascular pathophysiological changes holds possibilities for developing clinical diagnostic methods and new therapeutic strategies. Here, we discuss the underlying molecular mediators that could be involved in vascular aging, e.

Up-regulation of p16 by miR-877-3p inhibits proliferation of bladder cancer.

Despite the recent studies which have shown that microRNA (miRNA) negatively regulates gene expression by silencing the expression of target genes, here we reported the new evidence of microRNA-mediated gene activation by targeting specific promoter sites. We identified a miR-877-3p binding site on the promoter site of tumor suppressor gene p16 which alters frequently in bladder cancer. Enforced expression of miR-877-3p could increase the expression of p16, which inhibit the proliferation and tumorigenicity of bladder cancer through cell cycle G1-phase arrest.

MicroRNA-576-3p inhibits proliferation in bladder cancer cells by targeting cyclin D1.

MicroRNAs (miRNAs) are small, endogenous RNAs that play important gene-regulatory roles by binding to the imperfectly complementary sequences at the 3'-UTR of mRNAs and directing their gene expression. Here, we first discovered that miR-576-3p was down-regulated in human bladder cancer cell lines compared with the non-malignant cell line. To better characterize the role of miR-576-3p in bladder cancer cells, we over-expressed or down-regulated miR-576-3p in bladder cancer cells by transfecting with chemically synthesized mimic or inhibitor.

Apigenin inhibits migration and invasion via modulation of epithelial mesenchymal transition in prostate cancer.

The mortality rate associated with prostate cancer is mainly due to metastases rather than primary organ‑confined disease. Decreasing the incidence of metastasis is important in treating prostate cancer. 4',5,7‑trihydroxyflavone (apigenin) has been demonstrated to be effective in inhibiting several types of cancer.

Meta-analysis of nonsteroidal anti-inflammatory drug intake and prostate cancer risk.

Background: Epidemiological studies of the association between nonsteroidal anti-inflammatory drug (NSAID) intake and the risk of prostate cancer still remain controversial. Therefore, we conducted a meta-analysis to evaluate the potential association between NSAID intake and prostate cancer risk.

Methods: Eligible studies were retrieved by both computerized searches and reviews of references.

MicroRNA-320c inhibits tumorous behaviors of bladder cancer by targeting Cyclin-dependent kinase 6.

Background: Increasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to human disease including cancer. Previous miRNA microarray analysis illustrated that miR-320c is down-regulated in various cancers. However, the roles of miR-320c in human bladder cancer have not been well elucidated.