Four MEX3 genes were assessed for mutations by COSMIC database. Prior to February 20, 2021, the characteristics of MEX3 in Table II, and the genetic alteration affecting MEX3 in lung cancer samples in Table III. We found that the regulatory mechanism types in tumors, including lung cancer, are mainly missense mutations. Further, in the regulatory mechanism types study of lung cancer, three regulatory mechanism types were found in Fig. 1, Point Mutations, Copy Number Variation (CNV), Gene Expression. While in these regulatory mechanism types, point mutations mainly occurred in MEX3B, with the highest mutation frequency being 1.06%; CNV was confirmed on MEX3A, with the highest mutation frequency 1.99%; Gene Expression (Overexpressed) was determined on MEX3A, with the highest frequency 14.03%. No translocations, insertions, deletions, or loss of heterozygosity were identified. In summary, the results indicate that the sequence or copy number of the MEX3 gene has not altered significantly, except for MEX3A overexpression, which revealed that it is stable and not easy to mutate, leading to malignant proliferation of tumor cells. It may explain the development of malignant tumors.
Oncomine™ database analysis revealed that MEX3 expression in tissues of NSCLC patients compared to normal. The column bar graph in Fig. 2 was derived from the expression of each gene in tumors of different pathological types. The analysis demonstrated that, compared with normal, expression of MEX3 mRNA were significantly overexpressed in different pathological types. It concluded that: MEX3C does not meet the conditions, and other subtypes are overexpressed. MEX3A20 can be found in LUAD, LUSC and large cell lung cancer (LCLC), MEX3B20 in LCLC and MEX3D21 in LUAD. Furthermore, under the same pathological type and different databases, the distinctions in MEX3 expression were summarized in Table IV.
The prognostic value of MEX3 mRNA expression was examined by Kaplan Meier-plotter [Lung Cancer] 2015 version. Firstly, Fig. 3a demonstrated the prognostic effect of MEX3A mRNA expression. Over-expressed of MEX3A had significantly poor prognosis of NSCLC patients (HR = 1.48; CI, 1.26–1.75; P = 2.9E-06), LUAD (HR = 1.74; CI, 1.36–2.22; P = 9.9E-06), but not in LUSC (HR = 1.00; CI, 0.73–1.36; P = 0.99). Secondly, the effect of MEX3B mRNA expression on prognosis was examined, once again, the survival curves of patients with NSCLC, LUAD, and LUSC were described (Fig. 3b). Over- expressed of MEX3B was associated with decreased OS in all NSCLC (HR = 1.37; CI, 1.17–1.62; P = 1.4E-04) and LUAD cases (HR = 1.32; CI, 1.04–1.68; P = 0.023), but not in patients with LUSC (HR = 1.05; CI, 0.77–1.42; P = 0.78). As indicated in Fig. 3c, the prognostic value of MEX3C mRNA expression was analyzed. In all patients with NSCLC (HR = 0.81; CI, 0.71–0.91; P = 7.8E-04) and LUAD (HR = 0.50; CI, 0.39–0.63; P = 5.6E-09), over-expressed was related to lower OS, but not to LUSC (HR = 0.87; CI, 0.69–1.11; P = 0.26). Finally, Fig. 3d demonstrates the prognostic effect of MEX3D mRNA expression. Over-expressed of MEX3D had statistical difference in patients with NSCLC (HR = 1.30; CI, 1.14–1.47; P = 5.2E-05), LUAD (HR = 2.13; CI, 1.67–2.72; P = 4.5E-10) and LUSC (HR = 0.76; CI, 0.60–0.96; P = 0.02).
The associations between MEX3 and clinic pathological characteristics in NSCLC patients were explored, also, including Pathological histology, Stage, American Joint Committee on Cancer (AJCC) classification T, Lymph node status (AJCC stage N), Gender, Smoking status and Chemotherapy. Grade, AJCC stage M and Radiotherapy cannot examined because of invalid samples. As demonstrated in Table V, Overexpressed of MEX3A, MEX3B, MEX3C and MEX3D were associated with significantly lower OS in NSCLC and LUAD, while Overexpressed of MEX3D was associated with significantly poorer OS in patients with LUSC. Next, MEX3A, MEX3C and MEX3D overexpressed were identified to significant poorer OS in stage I, while MEX3C also has a consistent prognosis in stage II in Table S1. MEX3A and MEX3B were significantly associated with classification 2,while MEX3A was associated with classification 1 and MEX3B was associated with classification 3༌shown in Table S2.
MEX3A was correlated with 0 lymph node status (Table S3), meanwhile, four MEX3s were correlated with gender (Table S4) in NSCLC patients. For MEX3A, it was significantly associated to smoking, but MEX3C and MEX3D no significant (Table S5). In contrast, MEX3 was not associated to prognosis with or without chemotherapy treatment in NSCLC patients (Table S6).
The relationship between MEX3 and the immune microenvironment of LUAD and LUSC, as well as information of tumor purity were obtained by TIMER 2.0 database. In LUAD, MEX3A was positively correlated with tumor purity and negatively correlated with the level of dendritic cell infiltration. MEX3B was positively correlated with tumor purity, CD4 + T cell and macrophage infiltration level. MEX3C, not only correlated with tumor purity, but also with CD8 + T cells, CD4 + T cells, macrophages, and neutrophils infiltration levels were positively correlated. Finally, we found that MEX3D has statistically related with tumor purity, but positively in CD4 + T cells, macrophages and neutrophils (Fig. 4a). In LUSC, similarly, MEX3A was shown to be positively correlated with tumor purity, B cells, negatively with CD4 + T cells. MEX3B and MEX3C were positively correlated in tumor purity, CD8 + T cells and CD4 + T cells. In addition, MEX3D has no signification on tumor purity, but positively correlates with CD4 + T cells and macrophages (Fig. 4b). Here, further, we assessed that overexpressed MEX3 had no statistically significant difference in the survival rate of NSCLC patients, regardless of whether it was 1 year, 3 years or 5 years (P > 0.05).