Construction of a Lactate-Related Prognostic Signature for Predicting Prognosis, Tumor Microenvironment, and Immune Response in Kidney Renal Clear Cell Carcinoma

Sun, Zhuolun; Wen, Tao; Guo, Xudong; Jing, Changying; Zhang, Mingxiao; Wang, Zhenqing; Kong, Feng; Suo, Ning; Jiang, Shaobo; Wang, Hanbo

doi:10.3389/fimmu.2022.818984

Cited by 51 publications

(47 citation statements)

References 63 publications

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“…For example, dysregulations or polymorphisms of PER1, PER2, PER3, CLOCK, BMAL1, CRY1, CRY2, and NPAS2 were common in ovarian cancer, prostate cancer, leukemia, gliomas, hepatocellular carcinoma, and colorectal cancer [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. In KIRC patients, bioinformatics methods found that the expression levels of some core clock genes were altered in correlation with the overall survival of patients [ 3 ]. However, there are few reports on the relationship between KIRC and other circadian genes in the circadian pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Kidney renal clear cell carcinoma (KIRC) is the most common histological subtype of renal cell carcinoma, accounting for 80–90% of all cases, with a high degree of immune infiltration [ 1 , 2 , 3 ]. A better understanding of the immune system and a discovery that tumors can take advantage of immune checkpoints to promote their survival and growth have resulted in the creation of immune checkpoint inhibitors (ICIs) [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

Wang

et al. 2022

Bioengineering

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Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent and deadly types of renal cancer in adults. Recent research has identified circadian genes as being involved in the development and progression of KIRC by altering their expression. This study aimed to identify circadian genes that are differentially expressed in KIRC and assess their role in KIRC progression. In KIRC, there were 553 differentially expressed rhythm genes (DERGs), with 300 up-regulated and 253 down-regulated DERGs. Functional enrichment analyses showed that DERGs were greatly enriched in the circadian rhythm and immune response pathways. Survival analyses indicated that higher expression levels of CSNK1E were related to shorter overall survival of KIRC patients, whereas lower expression levels of GNA11, KLF9, and THRAP3 were associated with shorter overall survival of KIRC patients. Through cell assay verification, the mRNA level of CSNK1E was significantly up-regulated, whereas the mRNA levels of GNA11, KLF9, and THRAP3 were dramatically down-regulated in KIRC cells, which were consistent with the bioinformatics analysis of KIRC patient samples. Age, grade, stage, TM classification, and CSNK1E expression were all shown to be high-risk variables, whereas GNA11, KLF9, and THRAP3 expression were found to be low-risk factors in univariate Cox analyses. Multivariate Cox analyses showed that CSNK1E and KLF9 were also independently related to overall survival. Immune infiltration analysis indicated that the proportion of immune cells varied greatly between KIRC tissues and normal tissue, whereas CSNK1E, GNA11, KLF9, and THRAP3 expression levels were substantially linked with the infiltration abundance of immune cells and immunological biomarkers. Moreover, interaction networks between CSNK1E/GNA11/KLF9/THRAP3 and immune genes were constructed to explore the stream connections. The findings could help us better understand the molecular mechanisms of KIRC progression, and CSNK1E/GNA11/KLF9/THRAP3 might be used as molecular targets for chronotherapy in KIRC patients in the near future.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

Wang

et al. 2022

Bioengineering

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“…Xie et al demonstrated that the enhanced expression of four lactate risk-related genes, SLC25A3 , HPDL , NDUFA13 , and NARS2 , was correlated with poor prognosis in patients with skin cutaneous melanoma (SKCM), while patients with risk-related gene expression may benefit more from immune checkpoint inhibitor (ICI) therapy ( Xie et al, 2022 ). Sun et al established a lactate-related prognostic signature (LRPS) for the prognosis of patients with kidney renal clear cell carcinoma (KIRC) based on lactate metabolism-related genes and confirmed that LRPS might be effective in predicting the prognosis of patients with KIRC and that patients with low FPB1 and HDAH expression but high TYMP expression had a poor prognosis ( Sun et al, 2022 ). In our study, we found that STAT4 was an independent prognostic factor for BC in terms of both OS and PFS.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Lactate Metabolism Score in Breast and Thyroid Cancers to Assist Immunotherapy via Large-Scale Transcriptomic Data Analysis

Wang

Chen

et al. 2022

Front. Pharmacol.

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Breast cancer (BC) and thyroid cancer (TC) have the highest rate of incidence, especially in women. Previous studies have revealed that lactate provides energetic and anabolic support to cancer cells, thus serving as an important oncometabolite with both extracellular and intracellular signaling functions. However, the correlation of lactate metabolism scores with thyroid and breast cancer immune characteristics remains to be systematically analyzed. To investigate the role of lactate at the transcriptome level and its correlation with the clinical outcome of BC and TC, transcriptome data of 1,217 patients with breast cancer (BC) and 568 patients with thyroid cancer (TC) were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets with their corresponding clinical and somatic mutation data. The lactate metabolism score was calculated based on a single-sample gene set enrichment analysis (ssGSEA). The results showed that lactate metabolism-related genes and lactate metabolism scores was significantly associated with the survival of patients with BRCA and THCA. Notably, the lactate metabolism scores were strongly correlated with human leukocyte antigen (HLA) expression, tumor-infiltrating lymphocyte (TIL) infiltration, and interferon (IFN) response in BC and TC. Furthermore, the lactate metabolism score was an independent prognostic factor and could serve as a reliable predictor of overall survival, clinical characteristics, and immune cell infiltration, with the potential to be applied in immunotherapy or precise chemotherapy of BC and TC.

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“…In addition, the relationship between the risk score and expression of the immune checkpoints was investigated by Spearman's correlation analysis. In this study, the immunophenoscore (IPS) was used to evaluate the responses to anti-CTLA4 and anti-PD1 treatment regimens using The Cancer Immunome Atlas (TCIA, https://tcia.at/ ) database [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of an Inflammatory Response-Related Gene Signature to Predict Survival and Immune Status in Glioma Patients

Yan

Gao

Jing

et al. 2022

Journal of Immunology Research

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Background. Glioma is the most common primary brain tumor with high mortality and poor outcomes. As a hallmark of cancers, inflammatory responses are crucial for their progression. The present study is aimed at exploring the prognostic value of inflammatory response-related genes (IRRGs) and constructing a prognostic IRRG signature for gliomas. Materials and Methods. We investigated the relationship between IRRGs and gliomas by integrating the transcriptomic data for gliomas from public databases. Differentially expressed IRRGs (DE-IRRGs) were identified in the GSE4290 cohort. Further, univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses were conducted to construct an IRRG signature using The Cancer Genome Atlas (TCGA) cohort. Gliomas from the Chinese Glioma Genome Atlas (CGGA) cohort were employed for independent validation. The performance of gene signature was assessed by survival and receiver operating characteristic curve analyses. The differences in clinical correlations, immune infiltrate types, immunotherapeutic response predictions, and pathway enrichment among subgroups were investigated via bioinformatic algorithms. Results. In total, 37 DE-IRRGs were determined, of which 31 were found to be associated with survival. Ultimately, eight genes were retained to construct an IRRG signature that further classified glioma patients into two groups; the high-risk group suffered a poorer outcome as compared to the low-risk group. Furthermore, the high-risk group was significantly correlated with several risk factors, including older age, higher tumor grade, IDH wild type, 1p19q noncodel, and MGMT unmethylation. The nomogram was constructed by integrating the risk scores and other independent clinical characteristics. Moreover, the high-risk group had a greater immune infiltration and was most likely to benefit from immunotherapy. Gene set enrichment analysis suggested that immune and oncogenic pathways were enriched in high-risk glioma patients. Conclusion. We constructed a signature composed of eight IRRGs for gliomas, which could effectively predict survival and guide decision-making for treatment.

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Construction of a Lactate-Related Prognostic Signature for Predicting Prognosis, Tumor Microenvironment, and Immune Response in Kidney Renal Clear Cell Carcinoma

Cited by 51 publications

References 63 publications

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

Characterization of Lactate Metabolism Score in Breast and Thyroid Cancers to Assist Immunotherapy via Large-Scale Transcriptomic Data Analysis

Identification of an Inflammatory Response-Related Gene Signature to Predict Survival and Immune Status in Glioma Patients

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