Distinguishable Prognostic Signatures of Left- and Right-Sided Colon Cancer: a Study Based on Sequencing Data

Liang, Liang; Zeng, Jiang‐Hui; Qin, Xin‐Gan; Chen, Junqiang; Luo, Dan; Chen, Gang

doi:10.1159/000491778

Cited by 50 publications

(38 citation statements)

References 61 publications

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“…This latter finding is consistent with results reported by Liang et al demonstrating that left-sided colon cancer in patients with advanced stages exhibit poorer survival than those with right-sided colon cancers. 36 However, we found that the ppCD8sig scores did not differ between males and female (online supplemental figure 4B) or age groups (online supplemental figure 4C). Altogether, TCGA analysis supports that the gene signature identified from our gene expression profiling can predict poorer survival and more aggressive clinicopathological features, and could be reflective of the level or the activity of CD8 + T cells in human CRC.…”

Section: Functional Enrichment Analysis Of Steadily Deregulated Genesmentioning

confidence: 67%

Differential gene expression of tumor-infiltrating CD8⁺T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis

Saleh

Nair

Toor

et al. 2020

J Immunother Cancer

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BackgroundCytotoxic CD8+ T cell-mediated response is the most important arm of adaptive immunity, which dictates the capacity of the host immune response in eradicating tumor cells. Due to tumor intrinsic and/or extrinsic factors, the density and function of CD8+ tumor-infiltrating lymphocytes (TILs) could be compromised, leading to poor prognosis and survival.MethodsUsing RNA-Seq, transcriptomes of sorted CD3+CD8+ TILs from treatment-naïve colorectal cancer (CRC) patients at advanced stages (III and IV) were compared with those from patients with early stages (I and II). A signature referred to as ‘poor prognosis CD8 gene signature (ppCD8sig)’ was identified and analyzed in The Cancer Genome Atlas CRC dataset. Scores for the ppCD8sig were calculated and classified as high, intermediate and low, and its prognostic significance was assessed using multivariate analysis and Cox proportional hazard model. Densities of CD3+ and CD8+ T cell infiltration in tumors from patients with high and low ppCD8sig scores were assessed by flow cytometry and immunostaining.ResultsGenes related to epigenetic regulation and response to hypoxia were upregulated in CD8+ TILs from patients with advanced stages, while genes related to T cell activation, cell proliferation and cell cycle were downregulated. Patients with high ppCD8sig score had poorer disease-specific survival (DSS) and shorter progression-free interval (PFI). The ppCD8sig was an independent prognostic indicator for DSS (HR 1.83, 95% CI 1.40 to 2.38, p<0.0001) and PFI (HR 1.42, 95% CI 1.04 to 1.93, p=0.026). Additionally, patients with high ppCD8sig score were more likely to have advanced stages (χ2 p<0.0001) and residual disease after primary therapy (χ2 p=0.046). Patients with high ppCD8sig score had reduced levels of CD3+ and CD8+ TILs and low Immunoscores (IS), compared to patients with low ppCD8sig score.ConclusionsOur data provided insights into the altered regulation of biological mechanisms and signaling pathways in CD8+ TILs during CRC progression, and revealed a gene signature as an independent prognostic indicator. Patients with high ppCD8sig score had lower levels of TILs and low IS. These data further confirm the prognostic value of the identified ppCD8sig and potentially highlight its clinical relevance.

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Section: Functional Enrichment Analysis Of Steadily Deregulated Genesmentioning

confidence: 67%

Differential gene expression of tumor-infiltrating CD8⁺T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis

Saleh

Nair

Toor

et al. 2020

J Immunother Cancer

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“…org/package=survivalROC; version 1.0.3), which provides an effective approach for evaluating time-dependent ROC using censored data. To quantitatively evaluate the prognostic value, the area under the curve (AUC) of the ROC curves was calculated (24,(43)(44)(45)(46)(47)(48).…”

Section: Risk Score Constructionmentioning

confidence: 99%

A predicted risk score based on the expression of 16 autophagy‑related genes for multiple myeloma survival

Zhu¹,

Wang

Zeng³

et al. 2019

Oncol Lett

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Autophagy has an important role in the pathogenesis of plasma cell development and multiple myeloma (MM); however, the prognostic role of autophagy-related genes (ARGs) in MM remains undefined. In the present study, the expression profiles of 234 ARGs were obtained from a Gene Expression Omnibus dataset (accession GSE24080), which contains 559 samples of patients with MM analyzed with 54,675 probes. Univariate Cox regression analysis identified 55 ARGs that were significantly associated with event-free survival of MM. Furthermore, a risk score with 16 survival-associated ARGs was developed using multivariate Cox regression analysis, including ATIC,

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“…Based on tumor location, COAD includes at least two types [3], left colon adenocarcinoma (LCOAD) and right colon adenocarcinoma (RCOAD). LCOAD refers to tumors from the splenic flexure of the colon to the sigmoid colon, and RCOAD refers to tumors between the ileocecal region and the transverse colon [4]. In addition to their different origins, LCOAD and RCOAD also have different clinical manifestations, histological types, molecular characteristics, prognoses, modes of metastasis, and treatment options [3], which are reflected in the following aspects.…”

Section: Introductionmentioning

confidence: 99%

Screening and Identification of Differentially Expressed Genes Expressed among Left and Right Colon Adenocarcinoma

Han

Zhang

Yang

et al. 2020

BioMed Research International

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Purpose. Colon adenocarcinoma (COAD) is the third most common malignancy globally and is further categorized as left colon adenocarcinoma (LCOAD) or right colon adenocarcinoma (RCOAD) depending on the location of the primary tumor. The therapeutic outcome and long-term prognosis for patients with COAD are less than satisfactory, and this may be associated with tumor location. Therefore, it is important to investigate the genetic differences in COAD at different sites. Patients and Methods. Public data associated with COAD were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using R software (version 3.5.3), and functional annotation of DEGs was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction network was constructed, hub genes were identified and analyzed, and data mining using Gene Expression Profiling Interactive Analysis (GEPIA) was conducted. Results. A total of 286 DEGs were identified between LCOAD and RCOAD. Additionally, 10 hub genes associated with COAD at different locations were screened, namely, CDKN2A, IGF1R, MDM2, SMAD3, SLC2A1, GRM5, PLCB4, FGFR1, UBE2V2, and TNFRSF10B. The expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) and solute carrier family 2 member 1 (SLC2A1) was significantly associated with pathological stage P<0.05. COAD patients with high expression levels of CDKN2A exhibited poorer overall survival (OS) times than those with low expression levels P<0.05. Conclusion. CDKN2A expression was significantly different between LCOAD and RCOAD and was closely related to the prognosis of COAD. It is of great value for further understanding of the pathogenesis of LCOAD and RCOAD.

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Distinguishable Prognostic Signatures of Left- and Right-Sided Colon Cancer: a Study Based on Sequencing Data

Cited by 50 publications

References 61 publications

Differential gene expression of tumor-infiltrating CD8⁺T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis

Differential gene expression of tumor-infiltrating CD8⁺T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis

A predicted risk score based on the expression of 16 autophagy‑related genes for multiple myeloma survival

Screening and Identification of Differentially Expressed Genes Expressed among Left and Right Colon Adenocarcinoma

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Distinguishable Prognostic Signatures of Left- and Right-Sided Colon Cancer: a Study Based on Sequencing Data

Cited by 50 publications

References 61 publications

Differential gene expression of tumor-infiltrating CD8+T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis

Differential gene expression of tumor-infiltrating CD8+T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis

A predicted risk score based on the expression of 16 autophagy‑related genes for multiple myeloma survival

Screening and Identification of Differentially Expressed Genes Expressed among Left and Right Colon Adenocarcinoma

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Product

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Differential gene expression of tumor-infiltrating CD8⁺T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis

Differential gene expression of tumor-infiltrating CD8⁺T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis