High tumor mutation burden indicates better prognosis in colorectal cancer patients with KRAS mutations

Wang, Jianlei; Song, Jianping; Liu, Zeyang; Zhang, Tingxiao; Liu, Yanfeng

doi:10.3389/fonc.2022.1015308

“…Most evidence indicated that TMB could be used to evaluate the predictive prognosis [ 20 , 21 ]. In the study, we analyzed the relationship of TMB with the somatic mutation landscape in the EC and ICI scores, but the result showed that the TMB showed no significant differences between the two groups ( Figure 3(a) ).…”

Section: Resultsmentioning

confidence: 99%

Activated Mast Cells Combined with NRF2 Predict Prognosis for Esophageal Cancer

Guo

¹

,

Shen

²

,

Sun

³

et al. 2023

Journal of Oncology

2

0

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Background. Esophageal cancer (EC) had the sixth-highest mortality rate of all cancers due to its poor prognosis. Immune cells and mutation genes influenced the prognosis of EC, but their combined effect on predicting EC prognosis was unknown. In this study, we comprehensively analyzed the immune cell infiltration (ICI) and mutation genes and their combined effects for predicting prognosis in EC. Methods. The CIBERSORT and ESTIMATE algorithms were used to analyse the ICI scape based on the TCGA and GEO databases. EC tissues and pathologic sections from Huai’an, China, were used to verify the key immune cells and mutation genes and their interactions. Results. Stromal/immune score patterns and ICI/gene had no statistical significance in overall survival (OS) ( p > 0.05 ). The combination of ICI and tumor mutation burden (TMB) showed that the high TMB and high ICI score group had the shortest OS ( p = 0.004 ). We recognized that the key mutation gene NRF2 was significantly different in the high/low ICI score subgroups ( p = 0.002 ) and positivity with mast cells (MCs) ( p < 0.05 ). Through experimental validation, we found that the MCs and activated mast cells (AC-MCs) were more infiltration in stage II/III ( p = 0.032 ; p = 0.013 ) of EC patients and that NRF2 expression was upregulated in EC ( p = 0.045 ). AC-MCs combined with NRF2 had a poor prognosis, according to survival analysis ( p = 0.056 ) and interactive analysis ( p = 0.032 ). Conclusions. We presume that NRF2 combined with AC-MCs could be a marker to predict prognosis and could influence immunotherapy through regulating PD-L1 in the EC.

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“…As displayed in a previous study, APC mutation was related to immune evasion in CRC [ 69 ], which was consistent with the favorable immunotherapy response in the low-score group. Furthermore, SYNE1 mutation has been linked to shorter overall survival in CRC patients with liver metastasis [ 70 ], and APC mutation exhibited longer overall survival [ 71 ]. These could be reasonable explanations for the poorer prognosis in the high-score group and the better prognosis in the low-score group.…”

Section: Discussionmentioning

confidence: 99%

Molecular subtyping and the construction of a predictive model of colorectal cancer based on ion channel genes

Ai,

Li,

Chen

et al. 2024

Eur J Med Res

1

0

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Purpose Colorectal cancer (CRC) is a highly heterogeneous malignancy with an unfavorable prognosis. The purpose of this study was to address the heterogeneity of CRC by categorizing it into ion channel subtypes, and to develop a predictive modeling based on ion channel genes to predict the survival and immunological states of patients with CRC. The model will provide guidance for personalized immunotherapy and drug treatment. Methods A consistent clustering method was used to classify 619 CRC samples based on the expression of 279 ion channel genes. Such a method was allowed to investigate the relationship between molecular subtypes, prognosis, and immune infiltration. Furthermore, a predictive modeling was constructed for ion channels to evaluate the ion channel properties of individual tumors using the least absolute shrinkage and selection operator. The expression patterns of the characteristic genes were validated through molecular biology experiments. The effect of potassium channel tetramerization domain containing 9 (KCTD9) on CRC was verified by cellular functional experiments. Results Four distinct ion channel subtypes were identified in CRC, each characterized by unique prognosis and immune infiltration patterns. Notably, Ion Cluster3 exhibited high levels of immune infiltration and a favorable prognosis, while Ion Cluster4 showed relatively lower levels of immune infiltration and a poorer prognosis. The ion channel score could predict overall survival, with lower scores correlated with longer survival. This score served as an independent prognostic factor and presented an excellent predictive efficacy in the nomogram. In addition, the score was closely related to immune infiltration, immunotherapy response, and chemotherapy sensitivity. Experimental evidence further confirmed that low expression of KCTD9 in tumor tissues was associated with an unfavorable prognosis in patients with CRC. The cellular functional experiments demonstrated that KCTD9 inhibited the proliferation, migration and invasion capabilities of LOVO cells. Conclusions Ion channel subtyping and scoring can effectively predict the prognosis and evaluate the immune microenvironment, immunotherapy response, and drug sensitivity in patients with CRC.

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“…In bladder cancer, a higher TMB indicates a longer survival time 22 . Wang et al noted that a high tumor mutation burden indicates a better prognosis in CRC patients with KRAS mutations 23 . The influence of TMB on the prognosis of patients differs among different types of tumors.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis reveals TSPEAR as a prognostic biomarker in colorectal cancer

Xue,

Peng,

Li

et al. 2024

J. Cancer

0

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Background: Colorectal cancer (CRC) is one of the most common malignant tumors and has high morbidity and mortality rates. Previous studies have shown that TSPEAR mutations are involved in the development and progression of gastric cancer and liver cancer. However, the role of TSPEAR in CRC is still unclear. Methods: In The Cancer Genome Atlas (TCGA) database, 590 CRC patients with complete survival information were analyzed. We assessed TSPEAR expression in a pan-cancer dataset from the TCGA database. Cox regression analysis was performed to evaluate factors associated with prognosis. Enrichment analysis via the R package “clusterProfiler” was used to explore the potential function of TSPEAR. The single-sample GSEA (ssGSEA) method from the R package “GSVA” and the TIMER database were used to investigate the association between the immune infiltration level and TSPEAR expression in CRC. The R package “maftools” was used to explore the association between tumour mutation burden (TMB) and TSPEAR expression in CRC. CCK-8 assays and cell invasion assays were used to detect the effect of TSPEAR and TGIF2 on the biological behavior of CRC cells. Results: Pan-cancer analysis revealed that TSPEAR was upregulated in CRC tissues compared to normal tissues and that high TSPEAR expression was associated with poorer overall survival (OS) ( p =0.0053). The expression of TSPEAR increased with increasing TNM stage, T stage, N stage, and M stage. The nomogram constructed with TSPEAR, age, and TNM stage showed better predictive value than TSPEAR, age, or TNM stage alone. Immune cell infiltration analysis revealed that high expression of TSPEAR was associated with lower immune cell infiltration. Tumor mutation burden (TMB) analysis indicated that high expression of TSPEAR was associated with lower TMB ( p =0.005), and high TMB was associated with shorter OS ( p =0.02). CCK-8 assays and cell invasion assays indicated that in vitro knockdown of TSPEAR inhibited the proliferation, migration, and invasion of CRC cells. In addition, TSPEAR expression may be regulated by the upstream transcription factor TGIF2. Conclusion: TSPEAR expression was higher in CRC tissues than in normal tissues. Its upregulation was significantly associated with a poor prognosis. Additionally, TSPEAR plays a significant role in tumor immunity and the biological behavior of CRC cells. Thus, TSPEAR may become a promising prognostic biomarker and therapeutic target for CRC patients.

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High tumor mutation burden indicates better prognosis in colorectal cancer patients with KRAS mutations

Cited by 10 publications

References 44 publications

Activated Mast Cells Combined with NRF2 Predict Prognosis for Esophageal Cancer

Activated Mast Cells Combined with NRF2 Predict Prognosis for Esophageal Cancer

Molecular subtyping and the construction of a predictive model of colorectal cancer based on ion channel genes

Comprehensive analysis reveals TSPEAR as a prognostic biomarker in colorectal cancer

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