A cuproptosis-related lncRNA signature identified prognosis and tumour immune microenvironment in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is a heterogeneous malignant tumor with high incidence, metastasis, and mortality. The imbalance of copper homeostasis can produce cytotoxicity and cause cell damage. At the same time, copper can also induce tumor cell death and inhibit tumor transformation. The latest research found that this copper-induced cell death is different from the known cell death pathway, so it is defined as cuproptosis. We included 539 KIRC samples and 72 normal tissues from the Cancer Genome Atlas (TCGA) in our study. After identifying long non-coding RNAs (lncRNAs) significantly associated with cuproptosis, we clustered 526 KIRC samples based on the prognostic lncRNAs and obtained two different patterns (Cuproptosis.C1 and C2). C1 indicated an obviously worse prognostic outcome and possessed a higher immune score and immune cell infiltration level. Moreover, a prognosis signature (CRGscore) was constructed to effectively and accurately evaluate the overall survival (OS) of KIRC patients. There were significant differences in tumor immune microenvironment (TIME) and tumor mutation burden (TMB) between CRGscore-defined groups. CRGscore also has the potential to predict medicine efficacy.

Case report: Bladder preserving after maximal transurethral resection of the bladder tumor combined with chemotherapy and immunotherapy in recurrent muscle-invasive bladder cancer patients: A report of two cases.

Background: Cisplatin-based neoadjuvant chemotherapy combined with radical cystectomy (RC) plus pelvic lymph node dissection (PLND) is the preferred treatment option for muscle-invasive bladder cancer (MIBC). However, some patients are unable to tolerate RC or may have postoperative complications after RC. And most patients have a strong desire for bladder-preserving treatment. There are no reports on the efficacy of maximal transurethral resection of the bladder tumor (TURBT) in combination with chemotherapy plus tislelizumab for bladder-preserving in recurrent MIBC patients. Case presentation: We report two cases diagnosed with recurrent MIBC who achieved pathological complete response (pCR) and bladder-preserving after maximal TURBT combined with chemotherapy plus tislelizumab. Conclusion: Postoperative immunotherapy should be considered for all patients with recurrent MIBC who are eligible for immunotherapy. In addition, high programmed death ligand-1 (PD-L1) expression, high tumor mutation burden (TMB), and TP53 mutation level can be combined to predict tislelizumab efficacy.

Characterization of 7-Methylguanosine Identified Biochemical Recurrence and Tumor Immune Microenvironment in Prostate Cancer.

Prostate cancer (PCa) has a high incidence rate, mortality rate, and biochemical recurrence (BCR) rate. 7-Methylguanosine (m7G), as one of the RNA modifications, has been considered to be actively involved in cancer-related translation disorders in recent years. Therefore, we first used The Cancer Genome Atlas (TCGA) database to identify prognosis and m7G-related long non-coding RNAs (lncRNAs). Then we randomly divided the samples into the training set and test set and then constructed and verified the m7G lnRNA prognostic model (m7Gscore) by the least absolute shrinkage and selection operator (LASSO) regression analysis. The m7Gscore has been proved to be an independent marker of BCR-free survival in patients with PCa. Furthermore, the m7Gscore was significantly correlated with the tumor immune microenvironment (TIME) and somatic mutation of PCa patients and had the potential to be an indicator for the selection of drug treatment. We also clustered TCGA cohort into three m7G-related patterns (C1, C2, and C3). The Kaplan-Meier survival analysis revealed that C1 had the best BCR-free survival and C3 had the worst. The TIME was also significantly distinct among the three m7G-related patterns. According to the TIME characteristics of the patterns, we defined C1, C2, and C3 as immune-desert phenotype, immune-inflamed phenotype, and immune-excluded phenotype, respectively.

Identification and Quantification of Necroptosis Landscape on Therapy and Prognosis in Kidney Renal Clear Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) has high morbidity and gradually increased in recent years, and the rate of progression once relapsed is high. At present, owing to lack of effective prognosis predicted markers and post-recurrence drug selection guidelines, the prognosis of KIRC patients is greatly affected. Necroptosis is a regulated form of cell necrosis in a way that is independent of caspase. Induced necroptosis is considered an effective strategy in chemotherapy and targeted drugs, and it can also be used to improve the efficacy of immunotherapy. Herein, we quantified the necroptosis landscape of KIRC patients from The Cancer Genome Atlas (TCGA) database and divided them into two distinct necroptosis-related patterns (C1 and C2) through the non-negative matrix factorization (NMF) algorithm. Multi-analysis revealed the differences in clinicopathological characteristics and tumor immune microenvironment (TIME). Then, we constructed the NRG prognosis signature (NRGscore), which contained 10 NRGs (PLK1, APP, TNFRSF21, CXCL8, MYCN, TNFRSF1A, TRAF2, HSP90AA1, STUB1, and FLT3). We confirmed that NRGscore could be used as an independent prognostic marker for KIRC patients and performed excellent stability and accuracy. A nomogram model was also established to provide a more beneficial prognostic indicator for the clinic. We found that NRGscore was significantly correlated with clinicopathological characteristics, TIME, and tumor mutation burden (TMB) of KIRC patients. Moreover, NRGscore had effective guiding significance for immunotherapy, chemotherapy, and targeted drugs.

Identification and Quantification of Iron Metabolism Landscape on Therapy and Prognosis in Bladder Cancer.

The morbidity of bladder cancer (BLCA) is high and has gradually elevated in recent years. BLCA is also characterized by high recurrence and high invasiveness. Due to the drug resistance and lack of effective prognostic indicators, the prognosis of patients with BLCA is greatly affected. Iron metabolism is considered to be a pivot of tumor occurrence, progression, and tumor microenvironment (TME) in tumors, but there is little research in BLCA. Herein, we used univariate COX regression analysis to screen 95 prognosis-related iron metabolism-related genes (IMRGs) according to transcription RNA sequencing and prognosis information of the Cancer Genome Atlas (TCGA) database. TCGA-BLCA cohort was clustered into four distinct iron metabolism patterns (C1, C2, C3, and C4) by the non-negative matrix factorization (NMF) algorithm. Survival analysis showed that C1 and C3 patterns had a better prognosis. Gene set variant analysis (GSVA) revealed that C2 and C4 patterns were mostly enriched in carcinogenic and immune activation pathways. ESTIMATE and single sample gene set enrichment analysis (ssGSEA) also confirmed the level of immune cell infiltration in C2 and C4 patterns was significantly elevated. Moreover, the immune checkpoint genes in C2 and C4 patterns were observably overexpressed. Studies on somatic mutations showed that the tumor mutation burden (TMB) of C1 and C4 patterns was the lowest. Chemotherapy response assessment revealed that C2 pattern was the most sensitive to chemotherapy, while C3 pattern was the most insensitive. Then we established the IMRG prognosis signature (IMRGscore) by the least absolute shrinkage and selection operator (LASSO), including 13 IMRGs (TCIRG1, CTSE, ATP6V0A1, CYP2C8, RNF19A, CYP4Z1, YPEL5, PLOD1, BMP6, CAST, SCD, IFNG, and ASIC3). We confirmed IMRGscore could be utilized as an independent prognostic indicator. Therefore, validation and quantification of iron metabolism landscapes will help us comprehend the formation of the BLCA immunosuppressive microenvironment, guide the selection of chemotherapeutic drugs and immunotherapy, and predict the prognosis of patients.