Low tumor purity is associated with poor prognosis, heavy mutation burden, and intense immune phenotype in colon cancer

Mao, Yihao; Feng, Qi Sheng; Zheng, Peng; Liu, Yang; Li, Tianyu; Xu, Yu; Zhu, Dexiang; Chang, Wenju; Ji, Meiling; Li, Ren; Ye, Wei; He, Guodong; Xu, Jiacheng

doi:10.2147/cmar.s171855

Cited by 92 publications

(95 citation statements)

References 45 publications

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“…Thus, high TMB values reflect a high predisposition to be the target of antitumor immunity. Consistent with our survival and drug sensitivity results, numerous studies confirmed that immunotherapy is more efficient in patients with high TMB than in patients with low TMB [43,44]. In our study, patients with a high expression of CXCR4 had a lower TMB than patients with a low CXCR4 expression, suggesting that patients with high expression of CXCR4 may be resistant to immunotherapy, thus explaining the worse prognosis.…”

Section: Discussionsupporting

confidence: 91%

“…Previous studies showed that patients with a high tumor purity have a better prognosis. A high stromal and immune score in tumor tissues are correlated with a lack of infiltration and function of chemotherapy drugs [42,43]. Consistently, our results showed that patients with high CXCR4 expression have a high IC50 response to three antitumor drugs.…”

Section: Discussionsupporting

confidence: 80%

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Chemokine receptor 4 expression is correlated with the occurrence and prognosis of gastric cancer

Wang

et al. 2020

FEBS Open Bio

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Gastric cancer (GC) is a common tumor with a low 5‐year survival rate. The chemokine receptor 4 (CXCR4) protein contributes to the progression and prognosis of GC, but the relationship between CXCR4 and immune infiltration, somatic copy number alteration (SCNA), tumor purity, tumor mutation burden (TMB), cytolytic activity (CYT), and drug sensitivity in GC is poorly understood. This study aimed to systematically explore the role of CXCR4 in GC. Microarray and RNA‐seq data were collected from the Gene Expression Omnibus and The Cancer Genome Atlas. Our analysis shows that CXCR4 is correlated with various types of immune cells. Patients with high CXCR4 expression had a higher fraction of B cells and CD8+ T cells, and a lower fraction of CD4+ T cells. In addition, high CXCR4 expression was associated with more advanced tumor stage, worse prognosis and higher stromal score, immune score, and cytolytic activity (P < 0.05). High CXCR4 expression also correlated with lower tumor purity and TMB. In summary, our analyses suggest that CXCR4 may affect the progression and prognosis of GC by influencing immune infiltration, TMB, CYT, tumor purity, and drug sensitivity.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 80%

Chemokine receptor 4 expression is correlated with the occurrence and prognosis of gastric cancer

Wang

et al. 2020

FEBS Open Bio

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“…The predictive validity can be significantly improved by integrating glioma purity into prognostic nomogram. Mao et al [13] have discovered that tumor purity exhibits a potential value for colorectal cancer prognostic stratification as well as adjuvant chemotherapy benefit prediction. The relatively worse survival in low purity colorectal cancer may attribute to higher mutation frequency in key pathways and purity-related microenvironmental changing.…”

Section: Discussionmentioning

confidence: 99%

Establishment and Evaluation of a 6-Gene Survival Risk Assessment Model Related to Lung Adenocarcinoma Microenvironment

Wang

Zhu

et al. 2020

BioMed Research International

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Objective. A survival risk assessment model associated with a lung adenocarcinoma (LUAD) microenvironment was established and evaluated to identify effective independent prognostic factors for LUAD. Methods. The public data were downloaded from the TCGA database, and ESTIMATE prediction software was used to score immune cells and stromal cells for tumor purity prediction. The samples were divided into the high-score group and the low-score group by the median value of the immune score (or stromal score). The Wilcoxon test was used for differential analysis. GO and KEGG enrichment analysis of differentially expressed genes (DEGs) was performed using “clusterProfiler” of R package. Meanwhile, univariate and multivariate regression analysis was performed on DEGs to construct a multivariate Cox risk regression model with variable gene expression levels as independent prognostic factors affecting a tumor microenvironment (TME) and tumor immunity. Results. This study found that LUAD patients with high immune cell (stromal cell) infiltration had better prognosis and were in earlier staging. Functional enrichment analysis revealed that most DEGs were related to the proliferation and activation of immune cells or stromal cells. A survival prediction model composed of 6 TME-related genes (CLEC17A, TAGAP, ABCC8, BCAN, FLT3, and CCR2) was established, and finally, the 6 feature genes closely related to the prognosis of LUAD were proved. The AUC value of the ROC curve in this model was 0.7, indicating that the model was reliable. Conclusion. Six genes related to the LUAD microenvironment have a predictive prognostic value in LUAD.

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“…TCGA and other large-scale tumor characterization efforts to date have applied pre-determined tumor purity cutoff levels to include predominantly high purity tumors in their studies. As a result, molecular drivers of disease progression specific to prognostically poor/low purity tumors are frequently missed [2,29], as recently realized for colon cancer [30] and gliomas [31].…”

Section: Discussionmentioning

confidence: 99%

Extensive Intratumor Proteogenomic Heterogeneity Revealed by Multiregion Sampling in High-Grade Serous Ovarian Tumor Specimens

Hunt

Bateman

Hood

et al. 2019

Preprint

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A series of 200 consecutive thin sections were generated from a high-grade serous ovarian tumor and laser microdissected four spatially separated "core" regions of tumor epithelium, along with tumor epithelium, stroma or whole tissue harvests at 200 µm intervals. These distinct tissue collections were analyzed by quantitative proteomics and RNA-Seq. Unsupervised analyses revealed co-clustering of tumor cores with enriched tumor epithelium, which were distinct from the enriched stroma and whole tumor collections. Strong correlations in protein and transcript abundance in tumor epithelium and stromal collections from neighboring thin sections were decreased in samples harvested just hundreds of microns apart. Stroma (mesenchymal) and tumor epithelium (differentiated) displayed a distinct association with ovarian cancer prognostic molecular sub-types with a 2-year difference in median survival. These data reveal substantial tumor microenvironment protein and transcript expression heterogeneity that directly bear on prognostic signatures and underscore the need to enrich cellular subpopulations for expression profiling.

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Low tumor purity is associated with poor prognosis, heavy mutation burden, and intense immune phenotype in colon cancer

Cited by 92 publications

References 45 publications

Chemokine receptor 4 expression is correlated with the occurrence and prognosis of gastric cancer

Chemokine receptor 4 expression is correlated with the occurrence and prognosis of gastric cancer

Establishment and Evaluation of a 6-Gene Survival Risk Assessment Model Related to Lung Adenocarcinoma Microenvironment

Extensive Intratumor Proteogenomic Heterogeneity Revealed by Multiregion Sampling in High-Grade Serous Ovarian Tumor Specimens

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