A Combined Epithelial Mesenchymal Transformation and DNA Repair Gene Panel in Colorectal Cancer With Prognostic and Therapeutic Implication

Huang, Xiaoliang; Liu, Jungang; Liu, Haizhou; Mo, Xianwei; Meng, Yongsheng; Zhang, Lihua; Deng, Yuqing; Zhang, Yawei; Tang, Weizhong

doi:10.3389/fonc.2020.595182

Cited by 6 publications

(4 citation statements)

References 49 publications

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“… 31 , 32 MSI, which is a clinically important tumour marker, occurs because of a functional defect in DNA mismatch repair in tumour tissues. 33 In 2017, the FDA approved the PD-1 inhibitor Keytruda for the treatment of patients with any solid tumour with MSI-H. This is the first immunotherapy that does not differentiate based on the tumour origin, but rather differentiates based on tumour markers.…”

Section: Discussionmentioning

confidence: 99%

GIMAP7 as a Potential Predictive Marker for Pan-Cancer Prognosis and Immunotherapy Efficacy

Qin¹,

Li²,

Huang³

et al. 2022

JIR

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Background: GIMAP, a GTP enzyme of immune-related proteins, plays a crucial role in immune mechanisms. Investigating GIMAP7 expression in pan-cancer can provide efficient guidance for predicting clinical prognosis and identifying novel immunotherapy targets. Methods: Gene expression in different tumour types and stages was analysed based on The Cancer Genome Atlas and the Genotype-Tissue Expression database. An immunohistochemical assay was used to explore the differences in GIMAP7 protein levels in different tumour types and stages. Further, the cBioPortal was used to obtain the genetic variation characteristics of GIMAP7. Kaplan-Meier analysis and multivariable Cox regression analysis were performed to assess the prognostic value of GIMAP7. The pathways affected by GIMAP7 were studied based on gene set enrichment analysis, and the correlation between GIMAP7 expression and immune infiltration was determined using the TIMER2 database and the CIBERSORT method. ESTIMATE was used to analyse the correlation between GIMAP7 expression and ESTIMATE, immune and stromal scores. In addition, the correlation between GIMAP7 and immunoregulators was analysed. Furthermore, tumour mutational burden and microsatellite instability were evaluated using Spearman correlation assay. Results: GIMAP7 expression was significantly low and predicted better survival status in most tumour types. GIMAP7 was positively correlated with the abundance of CD8 + and CD4 + T cells in the tumour microenvironment. However, the high expression of GIMAP7 was negatively correlated with tumour mutations in uveal melanoma and colon adenocarcinoma. A correlation between GIMAP7 and microsatellite instability was found in rectal adenocarcinoma. Additionally, GIMAP7 presented a robust correlation between immune modulators and immunotherapeutic markers. Moreover, high GIMAP7 expression was significantly related to immune-relevant pathways. Conclusion:This study suggests the potential role of GIMAP7 as a prognostic and immunotherapeutic marker in pan-cancer, laying the groundwork for prospective functional and mechanistic experiments and their impact in the clinical setting.

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Section: Discussionmentioning

confidence: 99%

GIMAP7 as a Potential Predictive Marker for Pan-Cancer Prognosis and Immunotherapy Efficacy

Qin¹,

Li²,

Huang³

et al. 2022

JIR

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“…Although individual EMT markers have prognostic value, the combination of multiple EMT markers has been reported as a superior tool for CRC clinical outcome stratification [ 6 , 49 ]. In a previous study, Roseweir et al .…”

Section: Discussionmentioning

confidence: 99%

The combined tumour-based Fascin/Snail and stromal periostin reveals the effective prognosis prediction in colorectal cancer patients

Jirapongwattana,

Thongchot,

Pongpaibul

et al. 2024

PLoS ONE

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Colorectal cancer (CRC) is the third most common malignancy cause of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) promotes cancer metastasis and a tumour-based Glasgow EMT score was associated with adverse clinical features and poor prognosis. In this study, the impact of using the established five tumour-based EMT markers consisting of E-cadherin (E-cad), β-catenin (β-cat), Snail, Zeb-1, and Fascin in combination with the stromal periostin (PN) on the prediction of CRC patients’ prognosis were invesigated. Formalin-fixed paraffin-embedded tissues of 202 CRC patients were studies the expressions of E-cad, β-cat, Snail, Zeb-1, Fascin, and PN by immunohistochemistry. Individually, cytoplasmic Fascin (Fc), cytoplasmic Snail (Sc), nuclear Snail (Sn), stromal Snail (Ss), and stromal PN (Ps) were significantly associated with reduced survival. A combination of Ps with Fc, Fs, and Sn was observed in 2 patterns including combined Fc, Fs, and Ps (FcFsPs) and Fc, Sn, and Ps (FcSnPs). These combinations enhanced the prognostic power compared to individual EMT markers and were independent prognostic markers. As the previously established scoring method required five markers and stringent criteria, its clinical use might be limited. Therefore, using these novel combined prognostic markers, either FcFsPs or FcSnPs, may be useful in predicting CRC patient outcomes.

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“…Instead, the worst prognosis was associated with the Cluster 2, showing a pattern of high expression in mesenchymal genes and low expression in epithelial and DNA repair genes. However, no significant difference in OS was reported for patients in Cluster 2 and 3, regardless of whether they received adjuvant therapy, while patients in Cluster 1, which had increased expression of epithelial markers but down-regulated DNA repair genes, might benefit from chemotherapy [ 231 ].…”

Section: Emt and Chemoresistance: An Open Issuementioning

confidence: 99%

Epithelial to Mesenchymal Transition: A Challenging Playground for Translational Research. Current Models and Focus on TWIST1 Relevance and Gastrointestinal Cancers

Greco

Rubbino

Morelli

et al. 2021

IJMS

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Resembling the development of cancer by multistep carcinogenesis, the evolution towards metastasis involves several passages, from local invasion and intravasation, encompassing surviving anoikis into the circulation, landing at distant sites and therein establishing colonization, possibly followed by the outgrowth of macroscopic lesions. Within this cascade, epithelial to mesenchymal transition (EMT) works as a pleiotropic program enabling cancer cells to overcome local, systemic, and distant barriers against diffusion by replacing traits and functions of the epithelial signature with mesenchymal-like ones. Along the transition, a full-blown mesenchymal phenotype may not be accomplished. Rather, the plasticity of the program and its dependency on heterotopic signals implies a pendulum with oscillations towards its reversal, that is mesenchymal to epithelial transition. Cells in intermixed EÛM states can also display stemness, enabling their replication together with the epithelial reversion next to successful distant colonization. If we aim to include the EMT among the hallmarks of cancer that could modify clinical practice, the gap between the results pursued in basic research by animal models and those achieved in translational research by surrogate biomarkers needs to be filled. We review the knowledge on EMT, derived from models and mechanistic studies as well as from translational studies, with an emphasis on gastrointestinal cancers (GI).

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A Combined Epithelial Mesenchymal Transformation and DNA Repair Gene Panel in Colorectal Cancer With Prognostic and Therapeutic Implication

Cited by 6 publications

References 49 publications

GIMAP7 as a Potential Predictive Marker for Pan-Cancer Prognosis and Immunotherapy Efficacy

GIMAP7 as a Potential Predictive Marker for Pan-Cancer Prognosis and Immunotherapy Efficacy

The combined tumour-based Fascin/Snail and stromal periostin reveals the effective prognosis prediction in colorectal cancer patients

Epithelial to Mesenchymal Transition: A Challenging Playground for Translational Research. Current Models and Focus on TWIST1 Relevance and Gastrointestinal Cancers

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