Abstract Introduction APC and TP53 are the two most regularly mutated genes in colon adenocarcinoma (COAD), especially in progressive malignancies and antitumoral immune response. The current bioinformatics analysis investigates the APC and TP53 gene expression profile in colon adenocarcinoma as a prognostic characteristic for survival, particularly concentrating on the correlated immune microenvironment. Methods Clinical and genetic data of colon cancer and normal tissue samples were obtained from The Cancer Genome Atlas (TCGA)-COAD and Genotype-Tissue Expression (GTEx) online databases, respectively. The genetic differential expressions were analyzed in both groups via the one-way ANOVA test. Kaplan–Meier survival curves were applied to estimate the overall survival (OS). P < 0.05 was fixed as statistically significant. On Tumor Immune Estimation Resource and Gene Expression Profiling Interactive Analysis databases, the linkage between immune cell recruitment and APC and TP53 status was assessed through Spearman's correlation analysis. Results APC and TP53 were found mutated in 66.74% and 85.71% of the 454 and 7 TCGA-COAD patients in colon and rectosigmoid junction primary sites, respectively with a higher log2-transcriptome per million reads compared to the GTEx group (318 samples in sigmoid and 368 samples in transverse). Survival curves revealed a worse significant OS for the high-APC and TP53 profile colon. Spearman's analysis of immune cells demonstrated a strong positive correlation between the APC status and infiltration of T cell CD4+, T cell CD8+, NK cell, and macrophages and also a positive correlation between status and infiltration of T cell CD4+, T cell CD8+. Conclusions APC and TP53 gene mutations prevail in colon cancer and are extremely associated with poor prognosis and shortest survival. The infiltrating T cell CD4+, T cell CD8+, NK cell, and macrophages populate the colon microenvironment and regulate the mechanisms of tumor advancement, immune evasion, and sensitivity to standard chemotherapy. More comprehensive research is needed to demonstrate these results and turn them into new therapeutic outlooks.
Abstract Immunotherapy has revolutionized cancer treatment by harnessing the power of the immune system to eliminate tumors. Immune checkpoint inhibitors (ICIs) block negative regulatory signals that prevent T cells from attacking cancer cells. Two key ICIs target the PD-1/PD-L1 pathway, which includes programmed death-ligand 1 (PD-L1) and its receptor programmed death 1 (PD-1). Another ICI targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). While ICIs have demonstrated remarkable efficacy in various malignancies, only a subset of patients respond favorably. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, play a crucial role in modulating immune checkpoints, including PD-1/PD-L1 and CTLA-4. This review summarizes the latest advancements in immunotherapy, highlighting the therapeutic potential of targeting PD-1/PD-L1 and CTLA-4 immune checkpoints and the regulatory role of miRNAs in modulating these pathways. Consequently, understanding the complex interplay between miRNAs and immune checkpoints is essential for developing more effective and personalized immunotherapy strategies for cancer treatment. Graphical Abstract
Colorectal cancer (CRC) and gastric cancer (GC) are major contributors to cancer-related mortality worldwide. Despite advancements in understanding molecular mechanisms and improved drug treatments, the overall survival rate for patients remains unsatisfactory. Metastasis and drug resistance are major challenges contributing to the high mortality rate in both CRC and GC. Recent research has shed light on the role of long noncoding RNAs (lncRNAs) in the development and progression of these cancers. LncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions with microRNAs (miRNAs) and proteins. They can serve as miRNA precursors or pseudogenes, modulating gene expression at transcriptional and post-transcriptional levels. Additionally, circulating lncRNAs have emerged as non-invasive biomarkers for the diagnosis, prognosis, and prediction of drug therapy response in CRC and GC. This review explores the intricate relationship between lncRNAs and CRC/GC, encompassing their roles in cancer development, progression, and chemoresistance. Furthermore, it discusses the potential of lncRNAs as therapeutic targets in these malignancies. The interplay between lncRNAs, miRNAs, and tumor microenvironment is also highlighted, emphasizing their impact on the complexity of cancer biology. Understanding the regulatory landscape and molecular mechanisms governed by lncRNAs in CRC and GC is crucial for the development of effective diagnostic and prognostic biomarkers, as well as novel therapeutic strategies. This review provides a comprehensive overview of the current knowledge and paves the way for further exploration of lncRNAs as key players in the management of CRC and GC.
Gastric cancer (GC) continues to pose a major health issue worldwide, and diagnoses made at advanced stages frequently result in unfavorable outcomes. The metastatic spread of GC presents substantial therapeutic challenges, necessitating a deeper understanding of the tumor microenvironment (TME) and its interactions with cancer cells. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression and have been identified as key factors in the metastasis of GC. This review explores the biogenesis and functional mechanisms of miRNAs, highlighting their dual roles as oncogenes and tumor suppressors in GC metastasis. We discuss specific miRNAs that facilitate metastatic progression by influencing key pathways related to invasion, angiogenesis, and immune evasion. Furthermore, we examine the potential of miRNAs as diagnostic and prognostic biomarkers, offering insights into their utility in timely identification and tailored therapeutic approaches. By elucidating the complex regulatory networks involving miRNAs, this review underscores their significance as both therapeutic targets and biomarkers in the management of gastric cancer.
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