Predicting prognosis, immunotherapy and distinguishing cold and hot tumors in clear cell renal cell carcinoma based on anoikis-related lncRNAs

Abstract

BackgroundClear cell renal cell carcinoma (ccRCC) is the most frequently occurring malignant tumor within the kidney cancer subtype. It has low sensitivity to traditional radiotherapy and chemotherapy, the optimal treatment for localized ccRCC has been surgical resection, but even with complete resection the tumor will be eventually developed into metastatic disease in up to 40% of localized ccRCC. For this reason, it is crucial to find early diagnostic and treatment markers for ccRCC.MethodsWe obtained anoikis-related genes (ANRGs) integrated from Genecards and Harmonizome dataset. The anoikis-related risk model was constructed based on 12 anoikis-related lncRNAs (ARlncRNAs) and verified by principal component analysis (PCA), Receiver operating characteristic (ROC) curves, and T-distributed stochastic neighbor embedding (t-SNE), and the role of the risk score in ccRCC immune cell infiltration, immune checkpoint expression levels, and drug sensitivity was evaluated by various algorithms. Additionally, we divided patients based on ARlncRNAs into cold and hot tumor clusters using the ConsensusClusterPlus (CC) package.ResultsThe AUC of risk score was the highest among various factors, including age, gender, and stage, indicating that the model we built to predict survival was more accurate than the other clinical features. There was greater sensitivity to targeted drugs like Axitinib, Pazopanib, and Sunitinib in the high-risk group, as well as immunotherapy drugs. This shows that the risk-scoring model can accurately identify candidates for ccRCC immunotherapy and targeted therapy. Furthermore, our results suggest that cluster 1 is equivalent to hot tumors with enhanced sensitivity to immunotherapy drugs.ConclusionCollectively, we developed a risk score model based on 12 prognostic lncRNAs, expected to become a new tool for evaluating the prognosis of patients with ccRCC, providing different immunotherapy strategies by screening for hot and cold tumors.

Identification of a Novel Oxidative Stress- and Anoikis-Related Prognostic Signature and Its Immune Landscape Analysis in Non-Small Cell Lung Cancer

“…Anoikis is a special type of programmed cell death that occurs when normal epithelial cells lose their connection with the extracellular matrix. This process helps eliminate misaligned or displaced cells, preventing the possibility of malignant tissue proliferation and influencing cancer development [35]. The study found that anoikis in fact can be adjusted by oxidative stress.…”

The cross-talk between macrophages and tumor cells as a target for cancer treatment

“…Compared with hematological cancers, which are effectively targeted in many cases by chimeric antigen receptor (CAR) T cells, treatment of solid tumors with CAR-T therapy owing to vascular remodeling, hypoxia, and acidosis is often less effective ( 7 , 57 , 80 , 120 , 129 , 177 ). Given the constant trafficking of monocytes into tumors, macrophage-based cell therapies may constitute a feasible alternative to overcome obstacles to treat solid tumors, associated with the use of CAR T cells ( 15 , 57 , 80 , 120 , 129 , 177 ). Thus, engineering macrophages to deliver cytokines or nanoparticles to the TME or equipping them with specific receptors may be a promising therapeutic approach.…”

“…Hot tumors are attributed to infiltration of TMEs mostly by T cells ( 15 – 17 ). They intensify the immune response, engaging it to recognize and attack tumor cells and produce a good response to immunotherapy, including that with immune checkpoint inhibitors ( 17 ).…”

“…Cold tumors, on the other hand, are characterized by deficient immune cell infiltration in the TME, resulting in evasion of immune detection and responses to immune effector cells via several mechanisms, such as immunosuppressive growth factors and cytokines produced by tumor cells. A hot TME is generally seen as more favorable than cold TME in the context of cancer treatment because it suggests that the immune system is aggressively combating the tumor ( 15 ). Furthermore, an altered-excluded tumor is characterized by TME infiltration of CD8 + T cells located at the edge of the invasive margin of the tumor dominated by an abnormal vasculature (and consequent hypoxia) and a dense stroma, while altered-immunosuppressed tumors are characterized by the presence of a low degree of immune infiltration and an immunosuppressive, often hypoxic TME that limits further recruitment of immune cells and promotes an expansion of tumor ( 9 , 10 , 13 – 17 ).…”

Development of anoikis-related long non-coding RNA signature associated with prognosis and immune landscape in cutaneous melanoma patients

“…A number of reports have pointed out the influence of anoikis-related genes or lncRNAs on immune infiltrating microenvironment [ 30 , 31 ]. However, the mechanism has not been reported in depth.…”