Prognosis and pain dissection of novel signatures in kidney renal clear cell carcinoma based on fatty acid metabolism-related genes

Abstract

Renal cell carcinoma (RCC) is a malignant tumor that is characterized by the accumulation of intracellular lipid droplets. The prognostic value of fatty acid metabolism-related genes (FMGs) in RCC remains unclear. Alongside this insight, we collected data from three RCC cohorts, namely, The Cancer Genome Atlas (TCGA), E-MTAB-1980, and GSE22541 cohorts, and identified a total of 309 FMGs that could be associated with RCC prognosis. First, we determined the copy number variation and expression levels of these FMGs, and identified 52 overall survival (OS)-related FMGs of the TCGA-KIRC and the E-MTAB-1980 cohort data. Next, 10 of these genes—FASN, ACOT9, MID1IP1, CYP2C9, ABCD1, CPT2, CRAT, TP53INP2, FAAH2, and PTPRG—were identified as pivotal OS-related FMGs based on least absolute shrinkage and selection operator and Cox regression analyses. The expression of some of these genes was confirmed in patients with RCC by immunohistochemical analyses. Kaplan–Meier analysis showed that the identified FMGs were effective in predicting the prognosis of RCC. Moreover, an optimal nomogram was constructed based on FMG-based risk scores and clinical factors, and its robustness was verified by time-dependent receiver operating characteristic analysis, calibration curve analysis, and decision curve analysis. We have also described the biological processes and the tumor immune microenvironment based on FMG-based risk score classification. Given the close association between fatty acid metabolism and cancer-related pain, our 10-FMG signature may also serve as a potential therapeutic target with dual effects on ccRCC prognosis and cancer pain and, therefore, warrants further investigation.

Prognostic prediction and immunotherapy response analysis of the fatty acid metabolism-related genes in clear cell renal cell carcinoma

“…We showed that the FAM-related risk score predicted OS efficiently in both TCGA and ICGC cohorts. Consistent with previous studies, high-risk patients had worse OS than low-risk patients and were susceptible to posterior clinical staging, suggesting that the FAM-related risk score can be used to identify high-risk patients and provide personalized treatment to improve outcomes [ [97] , [98] , [99] , [100] ].…”

Cross-species single-cell transcriptomic analysis of animal gastric antrum reveals intense porcine mucosal immunity

“…1 E and F). The genes related to lipid metabolism were detected in rat and mouse epithelium, such as MID1IP1 (Ding et al 2022 ; Gaudet et al 2011 ), HMGCS1 (Rokosz et al 1994 ), SC5D (Matsushima et al 1996 ) and IDI1 (Gaudet et al 2011 ) in rat, and ALDH3A1 (Lee et al 2019 ), CLPS (Davis et al 1991 ), MOGAT1 (Gaudet et al 2011 ) and GDE1 (Zheng et al 2000 ) in mouse (Fig. 1 E and F).…”

Recent Advances in the Management of Clear Cell Renal Cell Carcinoma: Novel Biomarkers and Targeted Therapies

“…Particularly, clear cell renal cell carcinoma is the most common histological subtype, representing 75–80% of all cases of RCC, and it is responsible for most of the morbidity and mortality of RCC [ 30 ]. It has the worst prognosis among all the most frequent RCC variants [ 31 , 32 ]. About 20–30% of patients have metastasis, and 30% of those with a localized carcinoma at an advanced stage will develop metastases [ 33 ].…”

“…It is diagnosed more often in males than in females—indeed, it is classified as the seventh most common malignancy among men. The survival rate is estimated at 60–70% after treatment in the initial stage of the disease, but the 5-year survival rate for advanced forms is poor with less than 10%, despite the progress in therapies [ 30 , 32 ]. Moreover, ccRCC has the highest mortality rate considering genitourinary cancers, and clinical outcomes are also not satisfactory due to drug resistance [ 37 ].…”

“…The increasing incidence is likely due to improved detection by means of imaging techniques, but it could also depend on a higher prevalence of risk factors related to lifestyle such as obesity, Particularly, clear cell renal cell carcinoma is the most common histological subtype, representing 75-80% of all cases of RCC, and it is responsible for most of the morbidity and mortality of RCC [30]. It has the worst prognosis among all the most frequent RCC variants [31,32]. About 20-30% of patients have metastasis, and 30% of those with a localized carcinoma at an advanced stage will develop metastases [33].…”