Exploration of the Key Proteins of High-Grade Intraepithelial Neoplasia to Adenocarcinoma Sequence Using In-Depth Quantitative Proteomics Analysis

Purpose. In this study, we aimed to provide a comprehensive description of typical features and identify key proteins associated with the high-grade intraepithelial neoplasia- (HIN-) adenocarcinoma (AC) sequence. Methods. We conducted tandem mass tag-based quantitative proteomic profiling of normal mucosa, HIN, and AC tissues. Protein clusters representative of the HIN-AC sequence were identified using heatmaps based on Pearson’s correlation analysis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, ClueGO plugin in Cytoscape, and the Metascape database. The prognostic value of the key proteins and their effects on the tumor microenvironment and consensus molecular subtype were explored based on The Cancer Genome Atlas. Results. We identified 536 proteins categorized into three clusters. Among the biological processes and pathways of the highly expressed proteins in the HIN-AC sequence, proteins were predominantly enriched in response to gut microbiota, cell proliferation, leukocyte migration, and extracellular matrix (ECM) organization events. SERPINH1 and P3H1 were identified as the key proteins that promote the HIN-AC sequence. In the correlation analysis of infiltrating immune cells, both SERPINH1 and P3H1 expression correlated negatively with tumor purity, while correlating positively with abundance of CD8+ T cells, B cells, macrophage/monocytes, dendritic cells, cancer-associated fibroblasts, endothelial cells, neutrophils, and natural killer cells. Furthermore, both SERPINH1 and P3H1 expression positively correlated with common immune checkpoints and mesenchymal molecular subtype. High P3H1 expression was associated with poor disease-free survival and overall survival. Conclusions. ECM-related biological processes and pathways are typical features of the HIN-AC sequence. SERPINH1 and P3H1 might be the key proteins in this sequence and be related to ECM remodeling and immune suppression status in CRC.

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Evaluating high-grade prostatic intraepithelial neoplasia as a predictor of outcome following radical prostatectomy

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4612 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4612-4612

Author(s):

P. M. Pierorazio ◽

S. M. Lambert ◽

T. R. McCann ◽

A. E. Katz ◽

C. A. Olsson ◽

...

Keyword(s):

Radical Prostatectomy ◽

Perineural Invasion ◽

Disease Free Survival ◽

Intraepithelial Neoplasia ◽

High Grade ◽

Free Survival ◽

Pathologic Stage ◽

Significant Difference ◽

The Relationship ◽

Disease Free

4612 Background: The presence of high-grade prostatic intraepithelial neoplasia (HGPIN) has been associated with future development of prostate cancer. High-grade intraepithelial neoplasia in other malignancies is associated with adverse outcome. This study examines the relationship between the presence of HGPIN in prostatectomy specimens, biochemical disease free survival (bDFS) and other cancer specific outcomes following radical retropubic prostatectomy (RRP). Methods: The Columbia University Urologic Oncology Database was reviewed and 2,522 were identified who had undergone radical prostatectomy from 1988 to 2005; 2,133 patients with or without HGPIN were included. Two-sample proportion analysis of means with 95% confidence intervals and ANOVA techniques were used to evaluate the relationship between HGPIN and pathologic stage, Gleason sum, perineural invasion, multifocality, extracapsular extension (ECE), margin status, and nodal status. Kaplan-Meier analysis with log-rank test and a multivariate Cox proportional hazard model controlling for preoperative PSA, Gleason sum and pathologic stage were used to assess differences in bDFS. Results: 1,885 of 2,133 (88.4%) patients demonstrated HGPIN. There was no significant difference in the distribution of pathologic stage or Gleason sum between the patients with and without HGPIN. The HGPIN-positive group had higher rates of perineural invasion (69.9 vs. 57.5%; p = 0.003), multifocality (63.0 vs. 38.4%; p = 0.000) and ECE (56.4% vs. 48.4%; p = 0.059). There was no statistically significant difference observed in nodal status or margin status between the two groups. Patients without HGPIN had an increased bDFS demonstrated by a predicted disease free survival of 73.6% versus 67.0% at 9 years (p = 0.045) with a median follow-up of 50 months. In the multivariate Cox hazard model HGPIN, PSA, Gleason sum and pathologic stage were validated as independent predictors of failure (p < 0.001). The risk of failure was 1.9 × greater in the HGPIN-positive group than the HGPIN-negative group (p=0.006). Conclusions: The presence of HGPIN in the radical prostatectomy specimen denotes a significantly higher rate of tumor multifocality, perineural invasion, ECE, and ultimately biochemical recurrence. No significant financial relationships to disclose.

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High Expression of microRNA-223 Indicates a Good Prognosis in Triple-Negative Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.630432 ◽

2021 ◽

Vol 11 ◽

Author(s):

Li Chen ◽

Xiuzhi Zhu ◽

Boyue Han ◽

Lei Ji ◽

Ling Yao ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cox Regression ◽

Molecular Subtype ◽

External Validation ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Locked Nucleic Acid ◽

Tnbc Subtype

PurposeMicroRNAs can influence many biological processes and have shown promise as cancer biomarkers. Few studies have focused on the expression of microRNA-223 (miR-223) and its precise role in breast cancer (BC). We aimed to examine the expression level of miR-223 and its prognostic value in BC.MethodsTissue microarray (TMA)-based miRNA detection in situ hybridization (ISH) with a locked nucleic acid (LNA) probe was used to detect miR-223 expression in 450 BC tissue samples. Overall survival (OS) and disease-free survival (DFS) were compared between two groups using the Kaplan-Meier method and Cox regression model.ResultsOS and DFS were prolonged in the high miR-223 expression group compared to the low miR-223 expression group (p < 0.0001 and p = 0.017, respectively), especially in patients with the triple-negative breast cancer (TNBC) subtype (p = 0.046 and p < 0.001, respectively). Univariate and multivariate Cox regression analyses revealed that TNM stage (p = 0.008), the molecular subtype (p = 0.049), and miR-223 (p < 0.001) were independently associated with OS and DFS. External validation was performed with the METABRIC and The Cancer Genome Atlas (TCGA) databases via online webtools and was consistent with the data described above.ConclusionsThis study provides evidence that high miR-223 expression at diagnosis is associated with improved DFS and OS for BC patients, especially those with the TNBC subtype. miR-223 is a valid and independent prognostic biomarker in BC.

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PRKCA Overexpression Is Frequent in Young Oral Tongue Squamous Cell Carcinoma Patients and Is Associated with Poor Prognosis

Cancers ◽

10.3390/cancers13092082 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2082

Author(s):

Thomas Parzefall ◽

Julia Schnoell ◽

Laura Monschein ◽

Elisabeth Foki ◽

David Tianxiang Liu ◽

...

Keyword(s):

Squamous Cell ◽

Early Onset ◽

Molecular Subtype ◽

Young Patients ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Protein Markers ◽

Oral Tongue ◽

Significant Differential Expression ◽

Mrna Enrichment

Oral tongue squamous cell carcinomas (OTSCCs) have an increasing incidence in young patients, and many have an aggressive course of disease. The objective of this study was to identify candidate prognostic protein markers associated with early-onset OTSCC. We performed an exploratory screening for differential protein expression in younger (≤45 years) versus older (>45 years) OTSCC patients in The Cancer Genome Atlas (TCGA) cohort (n = 97). Expression of candidate markers was then validated in an independent Austrian OTSCC patient group (n = 34) by immunohistochemistry. Kaplan–Meier survival estimates were computed, and genomic and mRNA enrichment in silico analyses were performed. Overexpression of protein kinase C alpha (PRKCA) was significantly more frequent among young patients of both the TCGA (p = 0.0001) and the Austrian cohort (p = 0.02), associated with a negative anamnesis for alcohol consumption (p = 0.009) and tobacco smoking (p = 0.02) and poorer overall survival (univariate p = 0.02, multivariate p< 0.01). Within the young subgroup, both overall and disease-free survival were significantly decreased in patients with PRKCA overexpression (both p < 0.001). TCGA mRNA enrichment analysis revealed 332 mRNAs with significant differential expression in PRKCA-upregulated versus PRKCA-downregulated OTSCC (all FDR ≤ 0.01). Our findings suggest that PRKCA overexpression may be a hallmark of a novel molecular subtype of early-onset alcohol- and tobacco-negative high-risk OTSCC. Further analysis of the molecular PRKCA interactome may decipher the underlying mechanisms of carcinogenesis and clinicopathological behavior of PRKCA-overexpressing OTSCC.

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SERPINE2 Overexpression Is Associated with Poor Prognosis of Urothelial Carcinoma

Diagnostics ◽

10.3390/diagnostics11101928 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1928

Author(s):

Hao-Wen Chuang ◽

Kan-Tai Hsia ◽

Jia-Bin Liao ◽

Chih-Ching Yeh ◽

Wei-Ting Kuo ◽

...

Keyword(s):

Multivariate Analysis ◽

Urothelial Carcinoma ◽

Mrna Expression ◽

Poor Prognosis ◽

Disease Free Survival ◽

Tissue Microarrays ◽

Study Data ◽

The Cancer Genome Atlas ◽

High Grade ◽

Pathologic Features

Recent studies have reported that SERPINE2 contributes to the development of various cancers. However, its association with urothelial carcinoma (UC) remains unclear. In this study, data on urinary bladder UC (UBUC) cases from The Cancer Genome Atlas (TCGA) database were used to investigate the prognostic value of SERPINE2 mRNA expression. Then, SERPINE2 expression was analyzed with tissue microarrays constructed from 117 upper tract UC (UTUC) and 84 UBUC tissue specimens using immunohistochemical staining. Results were compared to clinicopathologic data by multivariate analysis. In the TCGA database, high SERPINE2 mRNA expression indicated a poor prognosis in patients with UBUC. Furthermore, Mann–Whitney U test showed that high SERPINE2 immunoexpression was significantly associated with adverse pathologic parameters including invasion, high grade, coexistence of UC in situ, and advanced pT stage (all p < 0.05, except for a marginal association with high-grade UBUC, p = 0.066). Kaplan–Meier analysis revealed that high SERPINE2 expression was associated with worse overall survival (OS; UTUC, p = 0.003; UBUC, p = 0.014) and disease-free survival (UTUC, p = 0.031; UBUC, p = 0.033). Moreover, multivariate analysis identified high SERPINE2 expression as an independent prognostic factor for OS (UTUC, p = 0.002; UBUC, p = 0.024). Taken together, our findings demonstrated that increased SERPINE2 expression is associated with adverse pathologic features and may serve as a prognostic biomarker for UC.

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Systematic Profiling of Diagnostic and Prognostic Value of Autophagy-Related Genes for Sarcoma Patients

10.21203/rs.3.rs-76971/v1 ◽

2020 ◽

Author(s):

Yuanhe Wang ◽

Jianyi Li ◽

Cheng Shao ◽

Xiaojie Tang ◽

Yukun Du ◽

...

Keyword(s):

Tumor Microenvironment ◽

Immune Cells ◽

Disease Free Survival ◽

Independent Set ◽

Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Differentially Expressed ◽

Immune Checkpoints ◽

Systematic Analysis

Abstract Background: Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking.Methods: Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. Results: In total, 84 DEIRGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between twp clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.636 for the OS and DFS nomograms, respectively.Conclusion: This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.

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Systematic profiling of diagnostic and prognostic value of autophagy-related genes for sarcoma patients

BMC Cancer ◽

10.1186/s12885-020-07596-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuanhe Wang ◽

Jianyi Li ◽

Cheng Shao ◽

Xiaojie Tang ◽

Yukun Du ◽

...

Keyword(s):

Tumor Microenvironment ◽

Immune Cells ◽

Disease Free Survival ◽

Independent Set ◽

Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Differentially Expressed ◽

Immune Checkpoints ◽

Systematic Analysis

Abstract Background Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking. Methods Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. Results In total, 84 DEARGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between two clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.747 for the OS and DFS nomograms, respectively. Conclusion This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.

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Systems-Level Proteomics Evaluation of Microglia Response to Tumor-Supportive Anti-inflammatory Cytokines

10.1101/2021.02.04.429830 ◽

2021 ◽

Author(s):

Shreya Ahuja ◽

Iulia M. Lazar

Keyword(s):

Cancer Cells ◽

Inflammatory Cytokines ◽

Antigen Processing ◽

Mitochondrial Gene ◽

Cellular Protein ◽

Biological Processes ◽

Proteomic Profiling ◽

Ecm Remodeling ◽

Collagen Formation ◽

Anti Inflammatory

AbstractBackgroundMicroglia safeguard the CNS against injuries and pathogens by inducing an inflammatory response. When exposed to anti-inflammatory cytokines, these cells possess the ability to switch from an inflammatory to an immunosuppressive phenotype. Cancer cells exploit this property to evade the immune system, and elicit an anti-inflammatory microenvironment that facilitates tumor attachment and growth.ObjectiveThe tumor-supportive biological processes that are activated in microglia cells in response to anti-inflammatory cytokines released from cancer cells were explored with mass spectrometry and proteomic technologies.MethodsSerum-depleted and non-depleted human microglia cells (HMC3) were treated with a cocktail of IL-4, IL-13, IL-10, TGFβ, and CCL2. The cellular protein extracts were analyzed by LC-MS/MS. Using functional annotation clustering tools, statistically significant proteins that displayed a change in abundance between cytokine-treated and non-treated cells were mapped to their biological networks and pathways.ResultsThe proteomic analysis of HMC3 cells enabled the identification of ∼10,000 proteins. Stimulation with anti-inflammatory cytokines resulted in the activation of distinct, yet integrated clusters of proteins that trigger downstream a number of tumor-promoting biological processes. The observed changes could be classified into four major categories, i.e., mitochondrial gene expression, ECM remodeling, immune response, and impaired cell cycle progression. Intracellular immune activation was mediated mainly by the transducers of MAPK, STAT, TGFβ, NFKB, and integrin signaling pathways. Abundant collagen formation along with the expression of additional receptors, matrix components, growth factors, proteases and protease inhibitors, enabled ECM remodeling processes supportive of cell-cell and cell-matrix adhesion. Overexpression of integrins and their modulators was reflective of signaling processes that correlated ECM reorganization with cytoskeletal re-arrangements supportive of cell migration. Antigen processing/presentation was represented by HLA class I histocompatibility antigens, and correlated with upregulated proteasomal subunits, and vesicular/viral transport and secretory processes. Immunosuppressive and proangiogenic chemokines were detectable in low abundance. Pronounced pro-inflammatory, chemotactic or phagocytic trends were not observed, however, the expression of certain receptors and ECM proteins indicated the presence of such capabilities.ConclusionsComprehensive proteomic profiling of HMC3 cells stimulated with anti-inflammatory cytokines revealed a microglia phenotype that provides novel insights into the tumor microenvironment-driven mechanisms that fuel cancer development in the brain.

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Significance of m 6A Methyltransferase‑Related lncRNAs in the Prognosis and Immunotherapy of Hepatocellular Carcinoma

10.21203/rs.3.rs-165071/v1 ◽

2021 ◽

Author(s):

Lili Li ◽

Rongrong Xie ◽

Qichun Wei

Keyword(s):

Hepatocellular Carcinoma ◽

Correlation Analysis ◽

Immune Cells ◽

Cox Regression ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Immune Checkpoints ◽

Regression Analyses ◽

Cox Regression Analysis

Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of mortality worldwide. N6-methyladenosine (m6A) methyltransferase, has been proved to act as an oncogene in several human cancers. However, little is known about its relationship with the long non-coding RNAs (lncRNAs) that remains elusive in HCC.Methods: We comprehensively integrated gene expression data acquired from 371 HCC and 50 normal tissues in The Cancer Genome Atlas (TCGA) database. Differentially expressed protein-coding genes (DE-PCGs)/lncRNAs (DE-lncRs) analysis and univariate regression & Kaplan-Meier (K-M) analysis was performed to identify m6A methyltransferase‑related lncRNAs that were related to overall survival (OS). m6A methyltransferase‑related lncRNA signature was constructed using the Least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Furthermore, Cox regression analysis was applied to identify independent prognostic factors in HCC. The signature was validated in an internal validation set. Finally, the correlation analysis between gene signature and immune cells infiltration was also investigated via single-sample Gene Set Enrichment Analysis (ssGSEA) and immunotherapy response was calculated through Tumor Immune Dysfunction and Exclusion (TIDE) algorithm.Results: A total of 21 m6A methyltransferase-related lncRNAs were screened out according to Spearman correlation analysis with the immune score (|R| > 0.3, P < 0.05). We selected 3 prognostic lncRNAs to construct m6A methyltransferase-related lncRNA signature through univariate and LASSO Cox regression analyses. The univariate and multivariate Cox regression analyses demonstrated that the lncRNAs signature was a robust independent prognostic factor in OS prediction with high accuracy. The GSEA also suggested that the m6A methyltransferase-related lncRNAs were involved in the immune-related biological processes and pathways which were very well-known in the context of HCC tumorigenesis. Besides, we found that the lncRNAs signature was strikingly correlated with the tumor microenvironment (TME) immune cells infiltration and expression of critical immune checkpoints. Finally, results from the TIDE analysis revealed that the m6A methyltransferase-related lncRNAs could efficiently predict the clinical response of immunotherapy in HCC.Conclusion: Together, our study screened potential prognostic m6A methyltransferase related lncRNAs and established a novel m6A methyltransferase-based prognostic model of HCC, which not only provides new potential prognostic biomarkers and therapeutic targets but also deepens our understanding of tumor immune microenvironment status and lays a theoretical foundation for immunotherapy.

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Systems-Level Proteomics Evaluation of Microglia Response to Tumor-Supportive Anti-Inflammatory Cytokines

Frontiers in Immunology ◽

10.3389/fimmu.2021.646043 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shreya Ahuja ◽

Iulia M. Lazar

Keyword(s):

Cancer Cells ◽

Inflammatory Cytokines ◽

Antigen Processing ◽

Mitochondrial Gene ◽

Cellular Protein ◽

Biological Processes ◽

Proteomic Profiling ◽

Ecm Remodeling ◽

Collagen Formation ◽

Anti Inflammatory

BackgroundMicroglia safeguard the CNS against injuries and pathogens, and in the presence of certain harmful stimuli are capable of inducing a disease-dependent inflammatory response. When exposed to anti-inflammatory cytokines, however, these cells possess the ability to switch from an inflammatory to an immunosuppressive phenotype. Cancer cells exploit this property to evade the immune system, and elicit an anti-inflammatory microenvironment that facilitates tumor attachment and growth.ObjectiveThe tumor-supportive biological processes that are activated in microglia cells in response to anti-inflammatory cytokines released from cancer cells were explored with mass spectrometry and proteomic technologies.MethodsSerum-depleted and non-depleted human microglia cells (HMC3) were treated with a cocktail of IL-4, IL-13, IL-10, TGFβ, and CCL2. The cellular protein extracts were analyzed by LC-MS/MS. Using functional annotation clustering tools, statistically significant proteins that displayed a change in abundance between cytokine-treated and non-treated cells were mapped to their biological networks and pathways.ResultsThe proteomic analysis of HMC3 cells enabled the identification of ~10,000 proteins. Stimulation with anti-inflammatory cytokines resulted in the activation of distinct, yet integrated clusters of proteins that trigger downstream a number of tumor-promoting biological processes. The observed changes could be classified into four major categories, i.e., mitochondrial gene expression, ECM remodeling, immune response, and impaired cell cycle progression. Intracellular immune activation was mediated mainly by the transducers of MAPK, STAT, TGFβ, NFKB, and integrin signaling pathways. Abundant collagen formation along with the expression of additional receptors, matrix components, growth factors, proteases and protease inhibitors, was indicative of ECM remodeling processes supportive of cell-cell and cell-matrix adhesion. Overexpression of integrins and their modulators was reflective of signaling processes that link ECM reorganization with cytoskeletal re-arrangements supportive of cell migration. Antigen processing/presentation was represented by HLA class I histocompatibility antigens, and correlated with upregulated proteasomal subunits, vesicular/viral transport, and secretory processes. Immunosuppressive and proangiogenic chemokines, as well as anti-angiogenic factors, were detectable in low abundance. Pronounced pro-inflammatory, chemotactic or phagocytic trends were not observed, however, the expression of certain receptors, signaling and ECM proteins indicated the presence of such capabilities.ConclusionsComprehensive proteomic profiling of HMC3 cells stimulated with anti-inflammatory cytokines revealed a spectrum of microglia phenotypes supportive of cancer development in the brain via microenvironment-dependent biological mechanisms.

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A novel prognostic immunoscore based on The Cancer Genome Atlas to predict overall survival in colorectal cancer patients

Bioscience Reports ◽

10.1042/bsr20210039 ◽

2021 ◽

Author(s):

Zuxiong Tang ◽

Yufan Wu ◽

Ding Sun ◽

Xiaofeng Xue ◽

Lei Qin

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cox Regression ◽

Disease Free Survival ◽

Clinical Information ◽

The Cancer Genome Atlas ◽

Immune Checkpoints ◽

The Novel ◽

Survival Times ◽

Specificity And Sensitivity

Colorectal cancer (CRC) is highly prevalent worldwide. The relationship between the infiltration of immunocytes in CRC and clinical outcome has been investigated in recent years. study aims to construct a new prognostic signature using an immunocyte panel. Our novel prognostic immunoscore included 13 types of immunocytes, which were identified by least absolute shrinkage and selection operator (LASSO)–Cox regression. The time-dependent receiver operating characteristic (ROC) curve and Kaplan–Meier survival estimates were applied to evaluate the prognostic ability. Compared with the signature based on a single immune marker (i.e., CD8 mRNA expression and CD8+ expressing T cells), the novel prognostic immunoscore possessed better specificity and sensitivity of prognosis (Area under the curves (AUCs) are 0.852, 0.856, and 0.774 for 1-, 2-, and 3-year survival times, respectively). Significant differences were identified between the high and low immunoscore groups in overall survival and disease-free survival in training and validation cohorts. Combining the immunoscore with clinical information may provide a more accurate prognosis for CRC. The immunoscore can identify patients with poor outcomes in the high Tumor Mutational Burden (TMB) group, who may benefit the most from immunotherapy. The immunoscore was also closely related to two immune checkpoints (i.e., PD-L1 and PD-1, r = 0.3087 and r = 0.3341, respectively). Collectively, Our study demonstrates that the novel prognostic immunoscore reported here may be useful in distinguishing different prognoses and may improve the clinical management of patients with CRC.

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