A Pan-Cancer Study of KMT2 Family as Therapeutic Targets in Cancer.

Weidong Mao,Dan Wu,Xiao Liang,Zhili Liu,Dong Shen,Jiamin Zhu,Lu Wang,Jimei Wang

doi:10.1155/2022/3982226

Abstract

Objective Exome sequencing studies have shown that the histone-lysine N-methyltransferase 2 (KMT2) gene is one of the most commonly mutated genes in a range of human malignancies and is linked to some of the most common and deadly solid tumors. However, the connection between this gene family's function and tumor type, immunological subtype, and molecular subtype dependency is still unknown. Methods We examine the expression patterns of the histone-lysine N-methyltransferase 2 (KMT2) gene, as well as their relationship to patient survival. We also used a pan-cancer analysis to link their function to immunological subtypes, the tumor microenvironment, and treatment sensitivity. Results Using the TCGA pan-cancer data, researchers looked at and examined KMT2 expression patterns and their links to patient survival and the tumor microenvironment in 33 cancer types. The expression of the KMT2 family changes significantly across and within cancer types, indicating significant inter- and intracancer heterogeneity. Patients' overall survival was often linked to the expression of KMT2 family members. However, the direction of the link differed depending on the KMT2 isoform and cancer type studied. Notably, in all cancer types examined, nearly all KMT2 family members were substantially linked with overall survival in patients with renal clear cell carcinoma (KIRC). Furthermore, all KMT2 genes have a strong relationship with immune infiltrate subtypes, as well as varying degrees of stromal cell infiltration and tumor cell stemness. Finally, we discovered that higher expression of KMT2s, particularly KMT2F and KMT2G, was linked to greater chemotherapeutic sensitivity in several cell lines. Conclusions The necessity to investigate each KMT2 member as a distinct entity inside each particular cancer type is highlighted by our comprehensive investigation of KMT2 gene expression and its relationship with immune infiltrates, tumor microenvironment, and cancer patient outcomes. Our research also confirmed the identification of KMT2 as a potential therapeutic target in cancer, but further laboratory testing is required.

Highlights

Epigenetics means that the DNA sequence does not change, but the gene expression changes heritably; that is, the genotype does not change, but the phenotype changes [1,2,3]
Expression of the KMT2 Gene in Various Cancers. To further understand their intrinsic expression pattern, we looked at the levels of expression of KMT2 family members in all cancer types available in TCGA pan-cancer data
While the expression levels of various KMT2 family members were positively correlated with each other averaged across cancer types using Spearman correlation tests, we discovered that the pairs KMT2C and KMT2A (r 0.78, P < 0.0001) and KMT2C and KMT2E (r 0.78, P < 0.0001) had the highest correlation among all the pairwise correlations of the 8 genes, implying that they may share some common features or functions (Figure 1(c))

Summary

Introduction

Epigenetics means that the DNA sequence does not change, but the gene expression changes heritably; that is, the genotype does not change, but the phenotype changes [1,2,3]. In other words, it is a way of inheritance outside of the DNA sequence. Histone-lysine N-methyltransferase 2(KMT2) family protein methylation lysine 4 in the tail of histone H3 is important for chromatin and DNA structural regulation [6].

Methods

Results

Discussion

Conclusion