Implication of Microsatellite Instability Pathway in Outcome of Colon Cancer in Moroccan Population

Agy, Fatima El; Otmani, Ihsane El; Mazti, Asmae; Lahmidani, Nada; Oussaden, Abdelmalek; Abkari, M. El; Benjelloun, El Bachir; Moukit, Wadih; Bouhaddouti, Hicham El; Toughraï, Imane; Hassani, Karim Ibn Majdoub; Maazaz, Khalid; Benbrahim, Zineb; Mellas, N.; Rhazi, K. El; Ouldim, Karim; Bardai, Sanae El; Ibrahimi, Sidhi Adil; Taleb, Khalid Ait; Bennis, S.; Chbani, Laïla

doi:10.1155/2019/3210710

Cited by 9 publications

(14 citation statements)

References 30 publications

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“…We observed that high tumor budding was more common in MSS tumors, which is consistent with ndings reported by previous studies (7,19,20). It was showed that MSS tumors were signi cantly correlated with shorter overall survival of CC patients (21).…”

Section: Discussionsupporting

confidence: 93%

Prognostic Impact of Tumor Budding on Moroccan Colon Cancer Patients

Fe¹,

Se²,

Bouguenouch³

et al. 2021

Preprint

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Background: Tumor budding is now emerging as one of the robust and promising histological factors that play an important role in colon cancer. In this study, we aimed to investigate the association between tumor budding and tumor clinicopathological factors, tumor molecular signature, and patient survival for the first time in the Moroccan population. Methods: We collected data of 100 patients with operated colon adenocarcinoma. Tumor budding was assessed on HES slides, according to the International Tumor Budding Consensus Conference 2016 recommendations. The expression of MMR proteins was performed by Immunohistochemistry. KRAS and NRAS mutations testing was performed by Sanger sequencing and pyrosequençing. Results: High tumor budding grade (BUD 3) was found to be significantly associated with adverse clinicopathological features including older age (P=0.03), presence of perineural invasion (P=0.02), presence of vascular invasion (P=0.05), distant metastases (P˂0.001), advanced TNM stage (P=0.001), the occurrence of relapse (P=0.04), and the high number of deceased cases (P=0.02). Interestingly, we found that tumors with high budding were more likely to be microsatellite stable (MSS) (P=0.005) and harbor more KRAS mutations (P=0.02). In all stages, High tumor budding was correlated with poorer overall survival (P=0.04) and decreased relapse-free survival with a difference close to significance ((P=0.09). we concluded that high tumor budding was strongly associated with unfavorable clinicopathological features and special molecular biomarkers and effectively affects the overall survival of CC patients. Conclusions: Based on these findings and the ITBCC group recommendations, tumor budding should be taken into account along with other clinicopathologic factors in the risk assessment of colorectal cancer.

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Section: Discussionsupporting

confidence: 93%

Prognostic Impact of Tumor Budding on Moroccan Colon Cancer Patients

Fe¹,

Se²,

Bouguenouch³

et al. 2021

Preprint

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“…Recently, the molecular epidemiological study conducted by Gonsalves et al [ 36 ] has shown that KRAS codon 13 mutations were associated with deficient mismatch repair phenotype and poor differentiation. These parameters were reported to be predictors of worse OS [ 37 ]. These results may explain the worse survival observed in patients with codon 13 mutations CC, as reported by Modest et al [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report

et al. 2021

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This study aimed to estimate the incidence of KRAS, NRAS, and BRAF mutations in the Moroccan population, and investigate the associations of KRAS and NRAS gene mutations with clinicopathological characteristics and their prognosis value. To achieve these objectives, we reviewed medical and pathology reports for 210 patients. RAS testing was investigated by Sanger sequencing and Pyrosequencing technology. BRAF (exon 15) status was analyzed by the Sanger method. The expression of MMR proteins was evaluated by Immunohistochemistry. KRAS and NRAS mutations were found in 36.7% and 2.9% of 210 patients, respectively. KRAS exon 2 mutations were identified in 76.5% of the cases. RAS-mutated colon cancers were significantly associated with female gender, presence of vascular invasion, classical adenocarcinoma, moderately differentiated tumors, advanced TNM stage III-IV, left colon site, higher incidence of distant metastases at the time of diagnostic, microsatellite stable phenotype, lower number of total lymph nodes, and higher means of positive lymph nodes and lymph node ratio. KRAS exon 2-mutated colon cancers, compared with KRAS wild-type colon cancers were associated with the same clinicopathological features of RAS-mutated colon cancers. NRAS-mutated patients were associated with lower total lymph node rate and the presence of positive lymph node. Rare RAS-mutated tumors, compared with wild-type tumors were more frequently moderately differentiated and associated with lower lymph node rate. We found that KRAS codon 13-mutated, tumors compared to codon 12-mutated tumors were significantly correlated with a higher death cases number, a lower rate of positive lymph, lower follow-up time, and poor overall survival. Our findings show that KRAS and NRAS mutations have distinct clinicopathological features. KRAS codon 13-mutated status was the worst predictor of prognosis at all stages in our population.

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“…Interestingly, MSI is now considered an indicator of tumor types in patients with COAD. In addition, COAD patients with high MSI showed better checkpoint inhibitor response and survival in both early and late clinical stages ( El Agy et al, 2019 ; Allan et al, 2020 ; Dzunic et al, 2020 ). In our study, both the TMB and MSI of COAD were positively correlated with the expression of MALT1, which supports our claim that MALT1 may be a good indicator of potential drug response (and MSI), as well as in COAD.…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis of MALT1 as a Potential Therapeutic Target for Prostate Cancer and its Immunological Role in Pan-Cancer

Tan

Xie

Zhang

et al. 2021

Front. Mol. Biosci.

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Background: Mucosa-associated lymphoma antigen 1 (MALT1) is an oncogene in subsets of diffuse large B cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue type (MALT) lymphoma. However, the role of MALT1 across cancers, especially in prostate cancer is still poorly understood.Methods: Here, we used several public datasets to evaluate MALT1 expression. Then, PCa cell lines and nude mice were used to investigate the cellular functions in vitro and in vivo. Microarray data were downloaded from The Cancer Genome Atlas and MALT1 was subjected to gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis to identify the biological functions and relevant pathways. Additionally, the correlations between MALT1 expression and mismatch repair (MMR) gene mutation, immune checkpoint gene expression, tumor mutational burden (TMB), and microsatellite instability (MSI) were investigated by Pearson correlation analysis. Moreover, the correlation between MALT1 expression and tumor immune infiltration was analyzed by the Tumor Immune Evaluation Resource (TIMER) database.Results: MALT1 overexpression was significantly correlated with MMR gene mutation levels and crucially promoted proliferation and colony genesis while reducing PCa cell apoptosis levels in vivo and in vitro. MALT1 expression showed strong correlations with immune checkpoint genes, TMB, and MSI in most cancers. The GO analysis indicated that MALT1-coexpressed genes were involved in heterotypic cell-cell adhesion, actin filament-based movement regulation, and action potential regulation. GSEA revealed that MALT1 expression was associated with several signaling pathways, including the NF-κB signaling, Wnt/β-catenin and TGF-β signaling pathways, in PCa. Additionally, MALT1 expression was significantly correlated with the infiltration of immune cells, including B cells, CD8+ T cells, dendritic cells and macrophages, and negatively correlated with CD4+ cell infiltration in PCa.Conclusion: MALT1 expression is higher in pancancer samples than in normal tissues. MALT1 promoted proliferation and colony genesis while reducing PCa cell apoptosis levels, and MALT1 suppression could inhibit xenograft tumor establishment in nude mice. Furthermore, MALT1 expression is closely related to the occurrence and development of multiple tumors in multiple ways. Therefore, MALT1 may be an emerging therapeutic target for a variety of cancers especially PCa.

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Implication of Microsatellite Instability Pathway in Outcome of Colon Cancer in Moroccan Population

Cited by 9 publications

References 30 publications

Prognostic Impact of Tumor Budding on Moroccan Colon Cancer Patients

Prognostic Impact of Tumor Budding on Moroccan Colon Cancer Patients

Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report

Integrative Analysis of MALT1 as a Potential Therapeutic Target for Prostate Cancer and its Immunological Role in Pan-Cancer

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