scholarly journals Correlate tumor mutation burden with immune signatures in human cancers

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaosheng Wang ◽  
Mengyuan Li
Keyword(s):  
Tumor Mutation Burden ◽  
Human Cancers ◽  
Immune Signatures ◽  
Mutation Burden

scholarly journals A Pan-Cancer Analysis of SLC12A5 Reveals Its Correlations with Tumor Immunity

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yi Jiang ◽  
Hong-li Liao ◽  
Li-ya Chen
Keyword(s):  
Tumor Immunity ◽  
Tumor Stage ◽  
Mechanisms Of Action ◽  
Solute Carrier Family ◽  
Tumor Mutation Burden ◽  
Human Cancers ◽  
Mutation Burden ◽  
Solute Carrier ◽  
Pan Cancer ◽  
Disease Specific

Background. Solute carrier family 12 member 5 (SLC12A5) has been reported to play an oncogenic role in certain malignancies. Its prognostic roles and immune mechanisms of action in human cancers, however, remain largely unknown. Methods. Data derived from TCGA, GEPIA, and TIMER databases were utilized to delve into the expressing patterns, prognostic values, clinical significances, and tumor immunity of SLC12A5 in tumors. Additionally, the association of SLC12A5 expressions with tumor mutation burden (TMB), methyltransferases, and mismatch repairs (MMRs) was also analyzed. Results. Herein, we observed that SLC12A5 was significantly overexpressed in various malignancies, and SLC12A5 levels correlated with overall survival, disease-specific survival, and tumor stage of certain cancers. Furthermore, we noticed that SLC12A5 was distinctly associated with methyltransferases, mismatch repair proteins, TMB, and MSI in human cancers. Conclusions. SLC12A5 may act as a potential prognostic and immunological biomarker and therapeutic target for human cancers.

Comprehensive assessment of PD-L1 and PD-L2 dysregulation in gastrointestinal cancers

Epigenomics ◽  
2020 ◽  
Author(s):  
Qijie Zhao ◽  
Jinan Guo ◽  
Yueshui Zhao ◽  
Jing Shen ◽  
Parham Jabbarzadeh Kaboli ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Signaling Pathways ◽  
Underlying Mechanism ◽  
Comprehensive Analysis ◽  
The Cancer Genome Atlas ◽  
Gastrointestinal Cancers ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Background: PD-L1 and PD-L2 are ligands of PD-1. Their overexpression has been reported in different cancers. However, the underlying mechanism of PD-L1 and PD-L2 dysregulation and their related signaling pathways are still unclear in gastrointestinal cancers. Materials & methods: The expression of PD-L1 and PD-L2 were studied in The Cancer Genome Atlas and Genotype-Tissue Expression databases. The gene and protein alteration of PD-L1 and PD-L2 were analyzed in cBioportal. The direct transcription factor regulating PD-L1/ PD-L2 was determined with ChIP-seq data. The association of PD-L1/PD-L2 expression with clinicopathological parameters, survival, immune infiltration and tumor mutation burden were investigated with data from The Cancer Genome Atlas. Potential targets and pathways of PD-L1 and PD-L2 were determined by protein enrichment, WebGestalt and gene ontology. Results: Comprehensive analysis revealed that PD-L1 and PD-L2 were significantly upregulated in most types of gastrointestinal cancers and their expressions were positively correlated. SP1 was a key transcription factor regulating the expression of PD-L1. Conclusion: Higher PD-L1 or PD-L2 expression was significantly associated with poor overall survival, higher tumor mutation burden and more immune and stromal cell populations. Finally, HIF-1, ERBB and mTOR signaling pathways were most significantly affected by PD-L1 and PD-L2 dysregulation. Altogether, this study provided comprehensive analysis of the dysregulation of PD-L1 and PD-L2, its underlying mechanism and downstream pathways, which add to the knowledge of manipulating PD-L1/PD-L2 for cancer immunotherapy.

scholarly journals Comprehensive analysis of genomic mutation signature and tumor mutation burden for prognosis of intrahepatic cholangiocarcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rui Zhang ◽  
Qi Li ◽  
Jialu Fu ◽  
Zhechuan Jin ◽  
Jingbo Su ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Cox Regression ◽  
Tnm Stage ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Tumor Mutation Burden ◽  
Kaplan Meier ◽  
Mutation Burden ◽  
Significant Difference ◽  
Genomic Mutation

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy of the biliary tract. Analysis of somatic mutational profiling can reveal new prognostic markers and actionable treatment targets. In this study, we explored the utility of genomic mutation signature and tumor mutation burden (TMB) in predicting prognosis in iCCA patients. Methods Whole-exome sequencing and corresponding clinical data were collected from the ICGC portal and cBioPortal database to detect the prognostic mutated genes and determine TMB values. To identify the hub prognostic mutant signature, we used Cox regression and Lasso feature selection. Mutation-related signature (MRS) was constructed using multivariate Cox regression. The predictive performances of MRS and TMB were assessed using Kaplan–Meier (KM) analysis and receiver operating characteristic (ROC). We performed a functional enrichment pathway analysis using gene set enrichment analysis (GSEA) for mutated genes. Based on the MRS, TMB, and the TNM stage, a nomogram was constructed to visualize prognosis in iCCA patients. Results The mutation landscape illustrated distributions of mutation frequencies and types in iCCA, and generated a list of most frequently mutated genes (such as Tp53, KRAS, ARID1A, and IDH1). Thirty-two mutated genes associated with overall survival (OS) were identified in iCCA patients. We obtained a six-gene signature using the Lasso and Cox method. AUCs for the MRS in the prediction of 1-, 3-, and 5-year OS were 0.759, 0.732, and 0.728, respectively. Kaplan–Meier analysis showed a significant difference in prognosis for patients with iCCA having a high and low MRS score (P < 0.001). GSEA was used to show that several signaling pathways, including MAPK, PI3K-AKT, and proteoglycan, were involved in cancer. Conversely, survival analysis indicated that TMB was significantly associated with prognosis. GSEA indicated that samples with high MRS or TMB also showed an upregulated expression of pathways involved in tumor signaling and the immune response. Finally, the predictive nomogram (that included MRS, TMB, and the TNM stage) demonstrated satisfactory performance in predicting survival in patients with iCCA. Conclusions Mutation-related signature and TMB were associated with prognosis in patients with iCCA. Our study provides a valuable prognostic predictor for determining outcomes in patients with iCCA.

scholarly journals ctDNA Clearance and Radiographic Resolution of Disease in Response to Dual Checkpoint Inhibition in Metastatic Microsatellite Stable Colorectal Cancer with a High Tumor Mutation Burden

2021 ◽  
pp. 849-853
Author(s):  
Charles J. Schneider ◽  
Michael Krainock ◽  
Allyson Koyen Malashevich ◽  
Meenakshi Malhotra ◽  
Perry Olshan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Ct Scan ◽  
Circulating Tumor Dna ◽  
Therapeutic Benefit ◽  
Tumor Mutation Burden ◽  
Early Treatment Response ◽  
Mutation Burden ◽  
Disease Present

Immunotherapy (IO) has increasingly been demonstrated to provide therapeutic benefit to patients with metastatic colorectal cancer (mCRC). However, only a subset of mCRC tumors respond to IO. Monitoring response with tumor biomarkers like carcinoembryonic antigen (CEA) has been challenging in patients with microsatellite stable (MSS) mCRC due to low expression of CEA (CEA/lo). Noninvasive blood-based biomarkers such as circulating tumor DNA (ctDNA) can inform early treatment response and augment radiographic monitoring. We describe a case study of a patient with chemotherapy-refractory CEA/lo MSS mCRC, with metastatic disease present in a cardiophrenic lymph node. The patient was given 2 cycles of combination IO (ipilimumab/nivolumab). Response was monitored by ctDNA using a multiplex PCR next-generation sequencing assay, CEA, and CT scan. After IO administration, ctDNA levels rapidly declined, becoming undetectable. This was concurrent with radiographic resolution of the lymph node metastasis. Serial monitoring of CEA during this same period was uninformative, with no significant changes observed. Significant decline in ctDNA identified metastatic response to IO in a patient with CEA/lo, MSS mCRC and was concurrently validated by CT scan. This case study provides evidence that ctDNA can be used as a prospective surrogate for radiographic tumor response.

scholarly journals Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67

2018 ◽  
Vol Volume 11 ◽  
pp. 2269-2275 ◽  
Author(s):  
Junnan Xu ◽  
Xiangyu Guo ◽  
Mingxi Jing ◽  
Tao Sun
Keyword(s):  
Breast Cancer ◽  
Ki 67 ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Her 2

scholarly journals Paired analysis of tumor mutation burden for lung adenocarcinoma and associated idiopathic pulmonary fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yasuto Yoneshima ◽  
Eiji Iwama ◽  
Shingo Matsumoto ◽  
Taichi Matsubara ◽  
Testuzo Tagawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Adenocarcinoma ◽  
Genetic Alterations ◽  
Driver Mutations ◽  
Somatic Variant ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
And Oxidative Stress

AbstractGenetic alterations underlying the development of lung cancer in individuals with idiopathic pulmonary fibrosis (IPF) have remained unclear. To explore whether genetic alterations in IPF tissue contribute to the development of IPF-associated lung cancer, we here evaluated tumor mutation burden (TMB) and somatic variants in 14 paired IPF and tumor samples from patients with IPF-associated lung adenocarcinoma. We also determined TMB for 22 samples of lung adenocarcinoma from patients without IPF. TMB for IPF-associated lung adenocarcinoma was significantly higher than that for matched IPF tissue (median of 2.94 vs. 1.26 mutations/Mb, P = 0.002). Three and 102 somatic variants were detected in IPF and matched lung adenocarcinoma samples, respectively, with only one pair of specimens sharing one somatic variant. TMB for IPF-associated lung adenocarcinoma was similar to that for lung adenocarcinoma samples with driver mutations (median of 2.94 vs. 2.51 mutations/Mb) and lower than that for lung adenocarcinoma samples without known driver mutations (median of 2.94 vs. 5.03 mutations/Mb, P = 0.130) from patients without IPF. Our findings suggest that not only the accumulation of somatic mutations but other factors such as inflammation and oxidative stress might contribute to the development and progression of lung cancer in patients with IPF.

RNF43 mutations to predict survival from treatment with immune checkpoint inhibitors and are associated with a high tumor mutation burden in bladder cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16528-e16528
Author(s):  
Liping Li ◽  
Mengmei Yang ◽  
Mengli Huang
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Negative Regulator ◽  
Wilcoxon Test ◽  
Wild Type ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
The Impact

e16528 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/L1 have been approved as first-line treatment for cisplatin-ineligible patients and as second-line therapy for patients with metastatic urothelial carcinoma of the bladder. Biomarkers can help select patients who are more likely to response to ICIs. RNF43 is an E3 ubiquitin ligase that acts as a negative regulator of Wnt/β-catenin signaling pathway. In colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs), RNF43 mutations predicted longer overall survival (OS). The impact of RNF43 mutations on the efficiency of ICIs in bladder cancer(BLC) remains to be explored. Methods: We downloaded the mutation and clinical data of 211 BLC patients treated with ICIs from the immunotherapeutic cohort published by Samstein et al. (2019). OS analyses were conducted using Kaplan-Meier curves and log-rank tests. Wilcoxon test was used for the comparison of TMB. We also downloaded a TCGA cohort for prognostic analysis. The correlations between RNF43 and immune infiltrates were analyzed in the TIMER2.0 database. Statistical significance was set at p = 0.05. Results: RNF43 mutations were identified in 4.3%(9/211) and 3%(13/438) BLC patients in the immunotherapeutic and TCGA cohort, respectively. In the immunotherapeutic cohort, patients with RNF43 mutations had significantly longer OS (25 months vs 8 months; p = 0.015) and higher tumor mutation burden(TMB, 42.3 vs 7.9; p = 3.15E-06) than RNF43-wild-type patients. Different from this, no significant difference was found in OS between RNF43-mutant and RNF43-wild-type BLC patients with standard treatment in the TCGA cohort (p = 0.696). These results indicated that RNF43 was not a prognostic factor but a predictive biomarker of survival in BLC treated with ICIs. No difference was observed in subsets of immune cells between RNF43-mutant and the RNF43-wide-type BLC patients, including neutrophils, macrophages, CD8+ T cells, Tregs, B cells and NK cells. Conclusions: RNF43 mutations may be a predictor of survival benefit from ICIs in bladder cancer and correlated with higher TMB. Further studies in other ICI-treated cohorts are needed to confirm these results.

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