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Introduction: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide and contributes significantly to cancer-related deaths. Since CRC is largely asymptomatic until alarm features develop to advanced stages, the incidence and mortality rate of CRC is relatively high and increases year by year. Areas covered: This review mainly summarizes the recent advances of genetic, epigenetic, and proteomic molecular markers that may be used to predict the prognosis of CRC. Moreover, we made an introduction to immune biomarkers and emerging microbial biomarkers. We also discussed the recent movement of molecular pathological epidemiology (MPE) in the context of prognostic biomarkers. Finally, we discussed the pros and cons of various biomarkers for improving prognostic judgment. Expert opinion: A great number of molecular targets have been identified as prognostic markers for CRC. However, because of some limitations, the efficiency of these biomarkers is restricted in clinical application. Combining a panel of several approaches may present a promising alternative tool for clinical practice. Further large-scale clinical trials are required to validate the prognostic value of these biomarkers in clinical use.

An important factor in tumor development and progression is the tumor microenvironment (TME), which is heterogeneous. Previous studies have mainly investigated the expression profile and prognostic values of genes in gastric cancer (GC) at the cell population level but neglected the interactions and heterogeneity between cells. The pattern of ligand–receptor (LR) interactions was delineated on a scRNA-seq dataset containing 44,953 cells from nine GC patients and a fourth bulk RNA-seq dataset including data from 1159 GC patients. We then constructed an LR.Score scoring model to comprehensively evaluate the influence of LR-pairs on the TME, overall survival, and immunotherapy response in GC patients from several cohorts. Cell communication network among 13 cell types was constructed based on the LR-pairs. We proposed a new molecular subtyping model for GC based on the LR-pairs and revealed the differences in prognosis, pathophysiologic features, mutation characteristics, function enrichment, and immunological characteristics among the three subtypes. Finally, an LR.Score model based on LR-pairs was developed and validated on several datasets. Based on the selected LR-pairs, we successfully constructed a novel prediction model and observed its well performance on molecular subtyping, target and pathway screening, prognosis judging, and immunotherapy response predicting. [ABSTRACT FROM AUTHOR]

The autophagy-associated transmembrane protein EI24 is associated with cancer growth and patient survival. We aimed to explore the prognostic role and immune infiltration characteristics of EI24 at a pan-cancer level. We collected data from multiple databases to explore the expression and prognostic role of EI24 in various cancers. Correlations between EI24 expression and DNA methylation, RNA modification, tumor mutation burden (TMB), microsatellite instability (MSI), immune moderator, immune checkpoint-related genes, the tumor immune microenvironment, and clinicopathological characteristics were analyzed. Finally, immunohistochemistry and western blotting were performed to validate the protein levels of EI24 in different tumors. Differential expression of EI24 was observed in most cancer types compared to non-cancerous tissues. EI24 showed a significant association with prognosis and may represent a new indicator of prognosis in patients with cancer. In most cancers, EI24 is closely associated with tumor immunity and interacts with various immune cells. Moreover, significant correlations were observed between EI24 expression and RNA modification, TMB, MSI, immune moderators, and immune checkpoint-related genes. This study provides new insights into the functions and clinical value of EI24 in different tumors and suggests that EI24 may serve as a promising biomarker or therapeutic target for cancer management. [ABSTRACT FROM AUTHOR]

Aim: To identify a potential prognostic signature of esophageal carcinoma based on autophagy-related genes (ARGs). Methods: RNA sequencing and clinical data were downloaded from the Cancer Genome Atlas. Significantly different ARGs were identified by Wilcoxon signed-rank test. A prognostic model was established employing Cox regression analysis. The model was evaluated by receiver operating characteristic and Kaplan-Meier curve. Results: A total of 28 significantly different ARGs were identified. Seven ARGs were screened to construct the prognostic model. The efficacy of the model was verified. A nomogram also validated the role of risk score in predicting prognosis. Enrichment analyses showed the possible underlying mechanisms. Conclusion: The seven-ARGs prognostic model was validated to be promising for predicting the prognosis of patients with esophageal carcinoma. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is a malignant cancer, the survival rate of patients is disappointing. Therefore, it is necessary to identify the driven-genes and prognostic biomarkers in OSCC. Methods: Four Gene Expression Omnibus (GEO) datasets were integratedly analyzed using bioinformatics approaches, including identification of differentially expressed genes (DEGs), GO and KEGG analysis, construction of protein-protein interaction (PPI) network, selection of hub genes, analysis of prognostic information and genetic alterations of hub genes. ONCOMINE, The Cancer Genome Atlas (TCGA) and Human Protein Atlas databases were used to evaluate the expression and prognostic value of hub genes. Tumor immunity was assessed to investigate the functions of hub genes. Finally, Cox regression model was performed to construct a multiple-gene prognostic signature. Results: Totally 261 genes were found to be dysregulated. 10 genes were considered to be the hub genes. The Kaplan-Meier analysis showed that upregulated SPP1, FN1, CXCL8, BIRC5, PLAUR, and AURKA were related to poor outcomes in OSCC patients. FOXM1 and TPX2 were considered as the potential immunotherapeutic targets with future clinical significance. Moreover, we constructed a nine-gene signature (TEX101, DSG2, SCG5, ADA, BOC, SCARA5, FST, SOCS1, and STC2), which can be utilized to predict prognosis of OSCC patients effectively. Conclusion: These findings may provide new clues for exploring the molecular mechanisms and targeted therapy in OSCC. The hub genes and risk gene signature are helpful to the personalized treatment and prognostic judgement. [ABSTRACT FROM AUTHOR]

The high mobility group box (HMGB) protein family consists of four members: HMGB1, 2, 3, and 4. They share similar amino acid sequences and identical functional regions, especially HMGB1, 2, and 3. The homology in structure may lead to similarity in function. In fact, though their targets may be different, they all possess the fundamental function of binding and distorting target DNAs. However, further research confirmed they are distributed differently in tissues and involved in various distinct physiological and pathological cellular processes, including cell proliferation, division, migration, and differentiation. Recently, the roles of HMGB family members in carcinogenesis has been widely investigated; however, systematic discussion on their functions and clinical values in malignant tumors is limited. In this review, we mainly review and summarize recent advances in knowledge of HMGB family members in terms of structure, distribution, biochemical cascades, and specific mechanisms regarding tumor progression. Importantly, the diagnostic, prognostic, and therapeutic value of these proteins in cancers is discussed. Finally, we envisage the orientation and challenges of this field in further studies. [ABSTRACT FROM AUTHOR]

Drug resistance, whether intrinsic or acquired, often leads to treatment failure in esophageal squamous cell carcinoma (ESCC). Clarifying the mechanism of drug resistance in ESCC has great significance for reversing drug resistance, as well as improving the prognosis of patients. Previously, we demonstrated that etoposide-induced 2.4-kb mRNA (EI24) is the target of miR-483-3p, which promoted the growth, migration, and drug resistance in ESCC, suggesting that EI24 participates in repressing the tumorigenesis and progression of ESCC. Here, we observed that EI24 was remarkably decreased in ESCC tissues. Moreover, its expression was directly linked to the prognosis of patients. We then confirmed that the forced overexpression of EI24 repressed cell growth and sensitized ESCC cells to chemotherapeutic agents, whereas EI24 silencing had the opposite effect. Furthermore, gene microarray and ingenuity pathway analysis (IPA) were performed to establish the potential mechanisms and indicated that EI24 exerts a tumor-suppressive role via suppressing the acute phase response signaling pathway or IL-1 signaling pathway in ESCC. Collectively, our data reveal that EI24 overexpression attenuates malignant phenotypes of ESCC and that it is a novel possible ESCC therapeutic target. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) serve an important role in cell differentiation, proliferation and apoptosis by negatively regulating gene expression at the transcriptional or post-transcriptional level. EI24 autophagy associated transmembrane protein (EI24) is a tumor suppressor gene that serves an important role in the occurrence and development of digestive system tumors. However, little is known regarding the relationship between EI24 and the prognosis of patients with colorectal cancer (CRC). Our previous study confirmed EI24 as the target molecule of miR-483, using reporter gene detection. Thus, the aim of the present study was to elucidate the effect of the abnormal expression of miR-483 on the malignant phenotype of CRC through a series of cell function experiments and nude mice tumorigenicity experiments, and to determine the expression level of EI24, a downstream target gene of miR-483, in CRC and its relationship with patient prognosis. In CRC tissues and cells, the expression level of miR-483 was upregulated, while the expression level of EI24 was downregulated. Cell function tests such as MTT assay, cell cycle assay, colony formation assay, Migration and invasion assays and nude mice tumorigenicity experiments demonstrated that the overexpression of miR-483 promoted the proliferation, invasion and metastasis of CRC. Moreover, the reverse transcription-quantitative PCR results indicated that overexpression of miR-483 inhibited the expression level of EI24. The relationship between the clinical data and immunohistochemical results from 183 patients with CRC and survival was examined. It was found that the expression level of EI24 was positively associated with the prognosis of patients. As a cancer-promoting factor, miR-483 enhances the proliferation, migration and invasion of CRC cells by reducing the expression level of EI24. [ABSTRACT FROM AUTHOR]