Distinct immune and inflammatory response patterns contribute to the identification of poor prognosis and advanced clinical characters in bladder cancer patients

Abstract

Due to the molecular heterogeneity, most bladder cancer (BLCA) patients show no pathological responses to immunotherapy and chemotherapy yet suffer from their toxicity. This study identified and validated three distinct and stable molecular clusters of BLCA in cross-platform databases based on personalized immune and inflammatory characteristics. H&E-stained histopathology images confirmed the distinct infiltration of immune and inflammatory cells among clusters. Cluster-A was characterized by a favorable prognosis and low immune and inflammatory infiltration but showed the highest abundance of prognosis-related favorable immune cell and inflammatory activity. Cluster-B featured the worst prognosis and high immune infiltration, but numerous unfavorable immune cells exist. Cluster-C had a favorable prognosis and the highest immune and inflammatory infiltration. Based on machine learning, a highly precise predictive model (immune and inflammatory responses signature, IIRS), including FN1, IL10, MYC, CD247, and TLR2, was developed and validated to identify the high IIRS-score group that had a poor prognosis and advanced clinical characteristics. Compared to other published models, IIRS showed the highest AUC in 5 years of overall survival (OS) and a favorable predictive value in predicting 1- and 3- year OS. Moreover, IIRS showed an excellent performance in predicting immunotherapy and chemotherapy’s response. According to immunohistochemistry and qRT-PCR, IIRS genes were differentially expressed between tumor tissues with corresponding normal or adjacent tissues. Finally, immunohistochemical and H&E-stained analyses were performed on the bladder tissues of 13 BLCA patients to further demonstrate that the IIRS score is a valid substitute for IIR patterns and can contribute to identifying patients with poor clinical and histopathology characteristics. In conclusion, we established a novel IIRS depicting an IIR pattern that could independently predict OS and acts as a highly precise predictive biomarker for advanced clinical characters and the responses to immunotherapy and chemotherapy.

TRP Ion Channels in Immune Cells and Their Implications for Inflammation

“…Growing evidence supports the involvement of TRP ion channels in certain diseases through inflammatory responses, including sepsis, colitis, pain, itch, allergy, asthma, atherosclerosis, and Alzheimer’s disease [ 28 , 37 , 62 , 77 , 97 , 98 ]. Moreover, TRP ion channels have also been implicated in obesity and diabetes as well as certain types of cancer via inflammation [ 5 , 64 , 85 , 99 , 100 ]. Recent studies have highlighted the participation of TRP ion channels in the infection process of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), suggesting their potential as therapeutic targets for SARS-CoV-2 and COVID-19 (coronavirus disease 2019) [ 24 , 101 , 102 , 103 ].…”

“…Acute inflammation refers to a transient response lasting only a few days, whereas chronic inflammation denotes a prolonged reaction. A prominent characteristic of inflammation is the accumulation and/or infiltration of immune cells (macrophages, lymphocytes, and plasma cells) at the site of injury, recruited from the circulation system through the continuous release of chemotactic factors by damaged tissues [ 3 , 4 , 5 , 6 ]. Pro-inflammatory factors encompass viruses, bacteria, physical trauma, injury, chemical agents, inappropriate immunological responses, and tissue necrosis.…”

The genetic associations of COVID-19 on genitourinary symptoms

“…Currently, the inflammatory and immune responses have been widely accepted as a double-edged sword, which can not only protect the body but also hurt it. The dysregulated inflammatory responses are associated with immune suppression, usually resulting in disease progression ( 52 – 54 ). Conversely, the normally controlled inflammation may initiate favorable immune responses, thus protecting the organism ( 52 , 55 ).…”

Identification of bladder cancer subtypes and predictive model for prognosis, immune features, and immunotherapy based on neutrophil extracellular trap-related genes

“…Despite the advancements in smoking cessation, surgery, and systemic therapy, encompassing chemotherapy and immunotherapy, the overall prognosis of individuals with BLCA has not witnessed any notable improvement in survival rates during recent years 27 , 28 . The association between the development of BLCA and the immunological characteristics of its tumor microenvironment is significant 29 , 30 . Consequently, it is imperative to investigate immune-related biomarkers for prognostic prediction and treatment guidance in BLCA patients.…”