Immune infiltration and immune gene signature predict the response to fluoropyrimidine-based chemotherapy in colorectal cancer patients

Mo, Xianwei; Huang, Xiaoliang; Yan, Feng; Wei, Chunyin; Liu, Haizhou; Ru, Haiming; Qin, Haiquan; Lai, Hao; Wu, Guan-Ling; Xie, Weishun; Jeen, Franco; Lin, Yuan; Liu, Jungang; Tang, Weizhong

doi:10.1080/2162402x.2020.1832347

Cited by 20 publications

(17 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased predicted sensitivity was concentrated in the CMS1, the MSI immune subtype. Our observation that inflammation-related gene sets are enriched in CMS1 tumors from obese patients is consistent with the finding that immune infiltration predicts fluoropyrimidine, a DNA replication-based chemotherapy (85). Our findings of differential CMS-dependent differences in predicted drug sensitivity are consistent with the observations that differential response to irinotecan-based compared to oxaliplatin-based chemotherapy (86) and chemotherapy plus bevacizumab compared cetuximab (7, 87) in metastatic CRC clinical trials are CMS-dependent.…”

Section: Discussionsupporting

confidence: 90%

Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis

Greene

Abraham

Kuhlers

et al. 2021

Preprint

View full text Add to dashboard Cite

Background Colorectal cancer (CRC) is the third-leading cause of cancer-related deaths in the United States and worldwide. Obesity, a worldwide public health concern, is a known risk factor for cancer including CRC. However, the mechanisms underlying the link between CRC and obesity have yet to be fully elucidated in part because of the molecular heterogeneity of CRC. We hypothesized that obesity modulates CRC in a consensus molecular subtype (CMS)-dependent manner. Methods RNA-seq data and associated tumor and patient characteristics including body weight and height data for 232 patients were obtained from The Cancer Genomic Atlas Colon Adenocarcinoma (TCGA-COAD) database. Tumor samples were classified into the four CMSs with the CMScaller R package; Body mass index (BMI) was calculated and categorized as normal, overweight, and obese. Results We observed a significant difference in CMS categorization between BMI categories. Differentially expressed genes (DEGs) between obese and overweight samples and normal samples differed across the CMSs, and associated prognostic analyses indicated that the DEGs had differing effects on survival. Using Gene Set Enrichment Analysis, we found differences in Hallmark gene set enrichment between obese and overweight samples and normal samples across the CMSs. We constructed Protein-Protein Interaction networks and observed differences in obesity-regulated hub genes for each CMS. Finally, we analyzed and found differences in predicted drug sensitivity between obese and overweight samples and normal samples across the CMSs. Conclusions Thus, we conclude that obesity has CMS-specific effects on the CRC tumor transcriptome.

show abstract

Section: Discussionsupporting

confidence: 90%

Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis

Greene

Abraham

Kuhlers

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…As Figure 4A indicated, PHF19 was correlated with the immune and stromal scores in KIRC, PRAD and THCA (all data P-values < 0.001). Since immune checkpoint-associated genes participate in the immunosuppressive mechanism that allows tumor cells to escape anti-tumor immunity ( 40 ), we next investigated the correlations between PHF19 expression and immune checkpoint-related genes, including BTLA, CD27, CD274, CD276, CD28, CD40, CD70, CD80, CD86, CTLA4, HAVCR2, HHLA2, ICOS, ICOSLG, IDO1, IDO2, LAG3, PDCD1, TIGIT, TNFRSF9, and TNFSF9 across human cancers from the TCGA cohorts, as shown in Figure 4B . Our results suggested that PHF19 expression was closely associated with almost all immune checkpoint-associated genes in BLCA, BRCA, HNSC, LIHC, PRAD and THCA, implying that PHF19 might conduce to immune escape in these tumors.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Pan-Cancer Genomic Analysis Reveals PHF19 as a Carcinogenic Indicator Related to Immune Infiltration and Prognosis of Hepatocellular Carcinoma

et al. 2022

View full text Add to dashboard Cite

BackgroundAs a crucial constituent part of Polycomb repressive complex 2, PHD finger protein 19 (PHF19) plays a pivotal role in epigenetic regulation, and acts as a critical regulator of multiple pathophysiological processes. However, the exact roles of PHF19 in cancers remain enigmatic. The present research was primarily designed to provide the prognostic landscape visualizations of PHF19 in cancers, and study the correlations between PHF19 expression and immune infiltration characteristics in tumor microenvironment.MethodsRaw data in regard to PHF19 expression were extracted from TCGA and GEO data portals. We examined the expression patterns, prognostic values, mutation landscapes, and protein-protein interaction network of PHF19 in pan-cancer utilizing multiple databases, and investigated the relationship of PHF19 expression with immune infiltrates across TCGA-sequenced cancers. The R language was used to conduct KEGG and GO enrichment analyses. Besides, we built a risk-score model of hepatocellular carcinoma (HCC) and validated its prognostic classification efficiency.ResultsOn balance, PHF19 expression was significantly higher in cancers in comparison with that in noncancerous samples. Increased expression of PHF19 was detrimental to the clinical prognoses of cancer patients, especially HCC. There were significant correlations between PHF19 expression and TMB or MSI in several cancers. High PHF19 levels were critically associated with the infiltration of myeloid-derived suppressor cells (MDSCs) and Th2 subsets of CD4+ T cells in most cancers. Enrichment analyses revealed that PHF19 participated in regulating carcinogenic processes including cell cycle and DNA replication, and was correlated with the progression of HCC. Intriguingly, GSEA suggested that PHF19 was correlated with the cellular components including immunoglobulin complex and T cell receptor complex in HCC. Based on PHF19-associated functional gene sets, an eleven-gene prognostic signature was constructed to predict HCC prognosis. Finally, we validated pan-cancer PHF19 expression, and its impacts on immune infiltrates in HCC.ConclusionThe epigenetic related regulator PHF19 participates in the carcinogenic progression of multiple cancers, and may contribute to the immune infiltration in tumor microenvironment. Our study suggests that PHF19 can serve as a carcinogenic indicator related to prognosis in pan-cancer, especially HCC, and shed new light on therapeutics of cancers for clinicians.

show abstract

“…Current research evidence suggests a significant influence of KRAS mutation in tumor immunity. An unsupervised hierarchical clustering analysis of immune genes/signatures named the Co-ordinate Immune Response Cluster (CIRC), comprising 28 genes, revealed a relatively high proportion of patients with KRAS mutation in the cluster associated with low inhibitory molecule expression [ 13 , 14 ]. In addition, immunophenotyping of colon tumors from mice indicated an association between Kras mutation and an immunosuppressive microenvironment characterized by decreased T-cell infiltration and increased infiltration of myeloid-derived suppressor cells (MDSCs) [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background KRAS gene is the most common type of mutation reported in colorectal cancer (CRC). KRAS mutation-mediated regulation of immunophenotype and immune pathways in CRC remains to be elucidated. Methods 535 CRC patients were used to compare the expression of immune-related genes (IRGs) and the abundance of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment between KRAS-mutant and KRAS wild-type CRC patients. An independent dataset included 566 cases of CRC and an in-house RNA sequencing dataset were served as validation sets. An in-house dataset consisting of 335 CRC patients were used to analyze systemic immune and inflammatory state in the presence of KRAS mutation. An immue risk (Imm-R) model consist of IRG and TIICs for prognostic prediction in KRAS-mutant CRC patients was established and validated. Results NF-κB and T-cell receptor signaling pathways were significantly inhibited in KRAS-mutant CRC patients. Regulatory T cells (Tregs) was increased while macrophage M1 and activated CD4 memory T cell was decreased in KRAS-mutant CRC. Prognosis correlated with enhanced Tregs, macrophage M1 and activated CD4 memory T cell and was validated. Serum levels of hypersensitive C-reactive protein (hs-CRP), CRP, and IgM were significantly decreased in KRAS-mutant compared to KRAS wild-type CRC patients. An immune risk model composed of VGF, RLN3, CT45A1 and TIICs signature classified CRC patients with distinct clinical outcomes. Conclusions KRAS mutation in CRC was associated with suppressed immune pathways and immune infiltration. The aberrant immune pathways and immune cells help to understand the tumor immune microenvironments in KRAS-mutant CRC patients.

show abstract

Immune infiltration and immune gene signature predict the response to fluoropyrimidine-based chemotherapy in colorectal cancer patients

Cited by 20 publications

References 76 publications

Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis

Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis

Comprehensive Pan-Cancer Genomic Analysis Reveals PHF19 as a Carcinogenic Indicator Related to Immune Infiltration and Prognosis of Hepatocellular Carcinoma

Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients

Contact Info

Product

Resources

About