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. 2022 Feb;10(2):241-254.
doi: 10.1002/iid3.557. Epub 2021 Nov 2.

The landscape of prognostic and immunological role of myosin light chain 9 (MYL9) in human tumors

Minghe Lv  1   2 , Lumeng Luo  1   2 , Xue Chen  1   2
Affiliations

The landscape of prognostic and immunological role of myosin light chain 9 (MYL9) in human tumors

Minghe Lv et al. Immun Inflamm Dis. 2022 Feb.

Abstract

Introduction: Recent studies have shown that myosin light chain 9 (MYL9) plays a vital role in immune infiltration, tumor invasion, and metastasis; however, the prognostic and immunological role of MYL9 has not been reported. The purpose of this study was to explore the potential prognostic and immunological roles of MYL9 in human cancers by public datasets mainly including the cancer genome atlas (TCGA) and Gene expression omnibus.

Methods: The expression pattern and prognostic value of MYL9 were analyzed across multiple public datasets in different cancer. The correlations between MYL9 expression and immune infiltration among multiple cancers were analyzed by using the TIMER2.0. The MYL9-related gene enrichment analysis was implemented by mainly using KEGG and GO datasets.

Results: MYL9 was lowly expressed in most cancers, such as breast cancer, lung adenocarcinoma and squamous cell carcinoma, and stomach adenocarcinoma; but it was highly expressed in several cancers, such as cholangiocarcinoma, head and neck squamous cell carcinoma, and liver hepatocellular carcinoma. Furthermore, MYL9 expression was distinctively associated with prognosis in adrenocortical carcinoma, colon adenocarcinoma, brain glioma, lung cancer, ovarian cancer, gastric cancer, breast cancer, blood cancer, and prostate cancer patients. The expressions of MYL9 were significantly associated with the infiltration of cancer-associated fibroblasts, B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, dendritic cell in different tumors as well as immune markers. In addition, we found that the functional mechanisms of MYL9 involved muscle contraction and focal adhesion.

Conclusion: MYL9 can serve as a prognostic signature in pan-cancer and is associated with immune infiltration. This pan-cancer study is the first to show a relatively comprehensive understanding of the prognostic and immunological roles of MYL9 across different cancers.

Keywords: MYL9; cancer; immune infiltration; prognosis.

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Figures

Figure 1
Figure 1
The expression level of myosin light chain 9 (MYL9) in different tumors. (A) The expression level of MYL9 in different types of cancer and normal tissues by using the Oncomine database (the threshold of the p value is .0001, fold change is 2, and gene ranking is top 10%). (B) The expression of the MYL9 gene was analyzed by TMIER 2.0 in different cancers. (C) The box plot of MYL9 gene expression was supplied for different tumors by using the TCGA and GTEx database. (D) The expression levels of the MYL9 gene were analyzed by the main pathological stages of colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), thyroid carcinoma (THCA), bladder urothelial carcinoma (BLCA), testicular germ cell tumors (TGCT), ovarian serous cystadenocarcinoma (OV), and stomach adenocarcinoma (STAD). Log2 (TPM + 1) was applied for log‐scale. * p < .05; ** p < .01; *** p < .001, **** p < .0001
Figure 2
Figure 2
The prognosis analysis of myosin light chain 9 (MYL9) gene expression in PrognoScan and Kaplan–Meier plotter datasets for different tumors. The effects of MYL9 expression on prognosis among various types of cancers in the PrognoScan dataset (A–L) and Kaplan–Meier database (M–T). DFS, disease‐free survival; DMFS, distant metastasis‐free survival; DSS, disease‐specific survival; FP, first progression; OS, overall survival; PFS: progression‐free survival; PPS: postprogression survival; RFS, relapse‐free survival
Figure 3
Figure 3
The expression level of myosin light chain 9 (MYL9) correlated with the immune infiltrating level of cancer‐associated fibroblasts. Through the EPIC, MCPCOUNTER, XCELL, and TIDE algorithms, the heatmap about the potential relationship between the infiltration level of different immune cells and MYL9 gene expression was exhibited by using the TIMER2.0 tool in different tumors. The heatmap (A), and the scatter plot (B) with the highest Spearman's p value results in four datasets were given
Figure 4
Figure 4
The expression of myosin light chain 9 (MYL9) was correlated with the immunological markers in gastric adenocarcinoma (STAD) and colon adenocarcinoma (COAD). (A–D) Scatter diagram of relations between the expression of MYL9 and the markers of monocytes (A), TAMs (B), M1 macrophage (C), and M2 macrophages (D) in STAD. (E–H) Scatter diagram of relations between the expression level of MYL9 and the markers of monocytes (E), TAM (F), M1 macrophage (G), and M2 macrophages (H) in COAD
Figure 5
Figure 5
The prognosis analysis of myosin light chain 9 (MYL9) gene expression and immune infiltration cells in different tumors. (A) The heatmap about multivariable Cox model analysis of MYL9, cancer‐associated fibroblasts, age, stage, gender, race, and purity for outcome in different tumors. The Kaplan–Meier curve of MYL9 expression and cancer‐associated fibroblast immune infiltrating in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) (B), HNS‐HPV+(C), kidney renal papillary cell carcinoma (KIRP) (D), brain lower grade glioma (LGG) (E), sarcoma (SARC) (F), and READ (G) via using the TIMER2.0 tool. The effects of the immune infiltrating of B cell, CD8+T cell, CD4+T cell, macrophage, neutrophil, dendritic cell, and the expression of MYL9 on cumulative survival in adrenocortical carcinoma (ACC) (H), bladder urothelial carcinoma (BLCA) (I), LGG (J), and mesothelioma (MESO) (K)
Figure 6
Figure 6
The enrichment analysis of the myosin light chain 9 (MYL9)‐related gene. (A) The available experimentally determined MYL9‐binding proteins were obtained by using the STRING tool. (B) The correlation analysis between the top 6 gene (TAGLN, CNN1, LMOD1, TPM2, KCNMB1, and JPH2) of those correlated with MYL9 expression and MYL9 via using GEPIA2. (C) The correlation analysis between the top 6 gene (TAGLN, CNN1, LMOD1, TPM2, KCNMB1, and JPH2) of those correlated with MYL9 expression and MYL9 via using TIMER 2.0. (D) Venn diagram showed an intersection analysis of the MYL9 binding and correlated genes. KEGG pathway analysis (E) and GO analysis (F) were performed based on the MYL9 binding and interacted genes
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