Objective: To explore the mutated genes in esophageal cancer (ESCA), and evaluate its relationship with tumor mutation burden (TMB) and prognosis of ESCA, and analyze the advantages of FAT3 as a potential prognostic marker in ESCA.Methods: The somatic mutation landscape was analyzed according to ESCA samples from the TCGA and ICGC database. The differences of TMB between mutant type and wild type of frequently mutated genes were compared by Mann-Whitney U test. The association of gene mutations with prognosis was analyzed by Kaplan-Meier method. The relative abundance of 22 tumor-infiltrating lymphocyte subsets in ESCA was calculated by CIBERSORT algorithm.Results: FAT3 was a high frequency mutation in both TCGA and ICGC samples from the somatic mutation landscape. Then, the mutation type of FAT3 had significantly higher TMB in patients with ESCA compared the wild type (P<0.05). Meanwhile, the prognosis of FAT3 mutation type was significantly worse in patients with ESCA(P<0.05), and the FAT3 mutation status might be an independent factor for prognosis of patients with ESCA (HR: 1.262–5.922, P=0.011). The GSEA analysis revealed the potential mechanism of FAT3 mutation on the occurrence and development of ESCA. Finally, naive B cells were significantly enriched in FAT3 mutation samples of the ESCA microenvironment (P<0.05).Conclusions: FAT3 mutation is related to TMB and poor prognosis in ESCA. FAT3 mutation may be a prognostic marker of ESCA, and reveal the potential mechanism of FAT3 mutation on ESCA.

Objective: To explore the expression of secreted phosphoprotein 1 (SPP1) in lung adenocarcinoma (LUAD), and evaluate its relationship with clinicopathological characteristics and prognosis of LUAD, and analyze the advantages of SPP1 as a potential prognostic marker in LUAD. Methods: The expression of SPP1 in normal lung tissue and LUAD was analyzed from the Cancer Cell Line Encyclopedia (CCLE), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA) databases. GSE68465 was used to explore the relationship between the SPP1 expression and clinicopathological characteristics and the prognosis of LUAD patients. The relationship between SPP1 and immune infiltration in LUAD was analyzed by the Tumor Immune Estimation Resource (TIMER) database. Gene enrichment analysis was performed in GSEA. The Cancer Genome Atlas (TCGA)-LUAD data was used to verify the results. Results: In the cell line level, non-small cell lung cancer ranked ninth among cancer cell lines based on SPP1 expression. In the messenger RNA (mRNA) and protein levels, SPP1 expression was higher in LUAD tissues than that in normal control. SPP1 expression was related to gender, N stage, histological grade, and progression or relapse. In men, SPP1 expression were higher compared to that in women. The higher the N stage, the higher the SPP1 expression level. As LUAD progresses or relapses, SPP1 expression could increase. In the pathological grade, the SPP1 expression was higher in LUAD samples with moderate differentiation. In addition, the overall 5-year survival rates of the SPP1 high and low expression groups were 50.574 and 59.181% [P = 0.008; hazard ratio (HR) = 0.7057; 95% CI, 0.5467–0.9109], indicating that SPP1 had an impact on overall survival for LUAD patients. The relationship between SPP1 expression and CD4⁺ T cell, macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. SPP1 could be considered as an independent prognostic marker in LUAD (P = 0.003; HR = 1.150; 95% CI, 1.048–1.261) by multivariate Cox regression analysis. The results of GSEA indicated that samples with high SPP1 expression were enriched in protein secretion, mTORC1 signaling, angiogenesis, and glycolysis pathway. The analysis results obtained by TCGA-LUAD data were basically consistent with the results obtained by GSE68465. Conclusions: SPP1 can not only affect the occurrence and development of LUAD but also may be an independent prognostic marker of LUAD. SPP1 is expected to be a new target for molecular targeted therapy.

Objective: To explore the lactate-related genes (LRGs) in lung adenocarcinoma (LUAD) by various methods, construct a prognostic model, and explore the relationship between lactate subtypes and the immune tumor microenvironment (TME). Methods: 24 LRGs were collected. The mutation landscape and the prognosis value of LRGs were explored by using The Cancer Genome Atlas (TCGA) data. Consensus clustering analysis was used for different lactate subtype identification. Based on the lactate subtypes, we explore the landscape of TME cell infiltration. A risk-score was calculated by using the LASSO-Cox analysis. A quantitative real-time PCR assay was utilized to validate the expression of characteristic genes in clinical cancer tissues and paracarinoma tissues from LUAD patients. Results: Comparing the normal samples, 18 LRGs were differentially expressed in tumor samples, which revealed that the differential expression of LRGs may be related to Copy Number Variation (CNV) alterations. The two distinct lactate subtypes were defined. Compared to patients in the LRGcluster A group, LUAD patients in the LRGcluster B group achieved better survival. The prognostic model was constructed based on differentially expressed genes (DEGs) via the LASSO-Cox analysis, which showed the accuracy of predicting the prognosis of LUAD patients using the ROC curve. A high-risk score was related to a high immune score, stromal score, and tumor mutation burden (TMB). Patients had better OS with low risk compared with those with high risk. The sensitivities of different risk groups to chemotherapeutic drugs were explored. Finally, the expression of characteristic genes in clinical cancer tissues and paracarinoma tissues from LUAD patients was verified via qRT-PCR. Conclusions: The lactate subtypes were independent prognostic biomarkers in LUAD. Additionally, the difference in the lactate subtypes was an indispensable feature for the individual TME. The comprehensive evaluation of the lactate subtypes in the single tumor would help us to understand the infiltration characteristics of TME and guide immunotherapy strategies.

Background: Although the majority of members belonging to the small GTPase Ras superfamily have been studied in several malignancies, the function of RBJ has remained unclear, particularly in non-small cell lung cancer (NSCLC). Objective: The research aims to determine the function of RBJ in NSCLC. Methods: The levels of RBJ protein in tumor tissue and para-carcinoma normal tissue were ascertained via immunohistochemistry (IHC). The growth, migration, and invasion of NSCLC cells were assessed by 5-ethynyl-2-deoxyuridine (EdU) assay, colony formation, cell counting kit-8 (CCK8), transwell and wound healing assays. Furthermore, a nude mouse xenograft model was established to study the function of RBJ in tumorigenesis in vivo. Results: The IHC analysis revealed that the protein levels of RBJ were notably increased in tumor tissue and positively associated with the clinical stage. In addition, the knockdown of RBJ restrained the growth, invasion, and migration of NSCLC cell lines by inhibiting the epithelial-mesenchymal transition (EMT) through the MEK/ERK signaling pathway. Accordingly, opposite results were observed when RBJ was overexpressed. In addition, the overexpression of RBJ accelerated tumor formation by A549 cells in nude mice. Conclusion: RBJ promoted cancer progression in NSCLC by activating EMT via the MEK/ERK signaling. Thus, RBJ could be used as a potential therapeutic against NSCLC.

Background/Objectives: PHF6 is a chromatin-binding protein located in the nucleus, and it is involved in transcriptional regulation. However, limited research exists on the specific roles and mechanisms of PHF6 across various tumors. Methods: Based on The Cancer Genome Atlas (TCGA) database, we analyzed PHF6 expression in pan-cancer. We first evaluated the relevance between PHF6 and prognosis; then, the relevance between PHF6 and immune cell infiltration in pan-cancer were analyzed. Subsequently, we explored the correlation between PHF6 and cancer heterogeneity, such as tumor mutation burden (TMB) and microsatellite instability (MSI), as well as cancer stemness. Finally, the role of PHF6 was validated in liver cancer and pancreatic cancer cell lines by cell proliferation assays. Results: PHF6 expression was higher in the vast majority of cancers than their normal counterparts. PHF6 was substantially correlated with prognosis and immune cell infiltration in various cancers. Moreover, PHF6 expression showed a strong correlation with cancer heterogeneity and stemness in certain cancer types. Additionally, the depletion of PHF6 inhibited cell proliferation in both liver and pancreatic cancer cells. Conclusions: PHF6 expression was closely associated with the occurrence and development of many types of cancer, and it might promote cancer progression by inhibiting the function of the immune microenvironment, while knockout of PHF6 significantly inhibited the tumor cells proliferation.