Age-, sex- and proximal-distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates.

The incidence of intestinal diseases increases with age, yet the mechanisms governing gut aging and its link to diseases, such as colorectal cancer (CRC), remain elusive. In this study, while considering age, sex and proximal-distal variations, we used a multi-omics approach in non-human primates (Macaca fascicularis) to shed light on the heterogeneity of intestinal aging and identify potential regulators of gut aging. We explored the roles of several regulators, including those from tryptophan metabolism, in intestinal function and lifespan in Caenorhabditis elegans.

Reactive oxygen species in colorectal cancer adjuvant therapies.

Colorectal cancer (CRC), a prevalent global malignancy, often necessitates adjuvant therapies such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy to mitigate tumor burden in advanced stages. The efficacy of these therapies is significantly influenced by reactive oxygen species (ROS). Previous research underscores the pivotal role of ROS in gut pathology, targeted therapy, and drug resistance.

Prediction of symptomatic anastomotic leak after rectal cancer surgery: A machine learning approach.

Introduction: Anastomotic leakage (AL) remains the most dreaded and unpredictable major complication after low anterior resection for mid-low rectal cancer. The aim of this study is to identify patients with high risk for AL based on the machine learning method.

Methods: Patients with mid-low rectal cancer undergoing low anterior resection were enrolled from West China Hospital between January 2008 and October 2019 and were split by time into training cohort and validation cohort.

Metastasis organotropism in colorectal cancer: advancing toward innovative therapies.

Distant metastasis remains a leading cause of mortality among patients with colorectal cancer (CRC). Organotropism, referring to the propensity of metastasis to target specific organs, is a well-documented phenomenon in CRC, with the liver, lungs, and peritoneum being preferred sites. Prior to establishing premetastatic niches within host organs, CRC cells secrete substances that promote metastatic organotropism.

Selenium metabolism heterogeneity in pan-cancer: insights from bulk and single-cell RNA sequencing.

Background: Selenium, a natural microelement with both nutritional and toxicological properties, is intertwined with tumorigenesis and progression. However, it is not fully understood how selenium metabolism affects immune response and cancer biology.

Methods: We estimated selenium metabolism by Gene Set Enrichment Analysis (GSEA) to delineate the selenium metabolism landscape using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and a integrated pan-cancer single-cell dataset.

Colorectal cancer liver metastasis: genomic evolution and crosstalk with the liver microenvironment.

Colorectal cancer (CRC) patients frequently develop liver metastases, which are the major cause of cancer-related mortality. The molecular basis and management of colorectal liver metastases (CRLMs) remain a challenging clinical issue. Recent genomic evidence has demonstrated the liver tropism of CRC and the presence of a stricter evolutionary bottleneck in the liver as a target organ compared to lymph nodes.

Deciphering the Clinical Significance and Kinase Functions of GSK3α in Colon Cancer by Proteomics and Phosphoproteomics.

GSK3α and GSK3β are two GSK3 isoforms with 84% overall identity and 98% identity in their catalytic domains. GSK3β plays important roles in the pathogenesis of cancer, while GSK3α has long been considered a functionally redundant protein of GSK3β. Few studies have specifically investigated the functions of GSK3α.

Amino acid metabolic reprogramming in tumor metastatic colonization.

Metastasis is considered as the major cause of cancer death. Cancer cells can be released from primary tumors into the circulation and then colonize in distant organs. How cancer cells acquire the ability to colonize in distant organs has always been the focus of tumor biology.

circNEIL3 inhibits tumor metastasis through recruiting the E3 ubiquitin ligase Nedd4L to degrade YBX1.

Distant metastasis is a major contributor to cancer-related mortality. However, the role of circRNAs in this process remains unclear. Herein, we profiled the circRNA expression in a cohort of 68 colorectal carcinoma (CRC) primary tumors and their paired liver metastatic lesions.

Phenotypic Heterogeneity Analysis of APC-Mutant Colon Cancer by Proteomics and Phosphoproteomics Identifies RAI14 as a Key Prognostic Determinant in East Asians and Westerners.

Adenomatous polyposis coli (APC) is an important tumor suppressor and is mostly linked to the regulation of the Wnt/β-catenin signaling pathway. APC mutation has been identified as an early event in more than 80% of sporadic colorectal cancers (CRCs). Moreover, prognostic differences are observed in CRC patients with APC mutations.

PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma.

Serine synthesis is crucial for tumor growth and survival, but its regulatory mechanism in cancer remains elusive. Here, using integrative metabolomics and transcriptomics analyses, we show a heterogeneity between metabolite and transcript profiles. Specifically, the level of serine in hepatocellular carcinoma (HCC) tissues is increased, whereas the expression of phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme in serine biosynthesis pathway, is markedly downregulated.

Targeting PSAT1 to mitigate metastasis in tumors with p53-72Pro variant.

The single-nucleotide polymorphism (SNP) of p53, in particular the codon 72 variants, has recently been implicated as a critical regulator in tumor progression. However, the underlying mechanism remains elusive. Here we found that cancer cells carrying codon 72-Pro variant of p53 showed impaired metastatic potential upon serine supplementation.

Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment.

Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy.

Disrupting metformin adaptation of liver cancer cells by targeting the TOMM34/ATP5B axis.

Metformin, a well-known antidiabetic drug, has been repurposed for cancer treatment; however, recently observed drug resistance and tumor metastasis have questioned its further application. Here, we found that long-term metformin exposure led to metabolic adaptation of hepatocellular carcinoma (HCC) cells, which was characterized by an obvious epithelial-mesenchymal transition (EMT) phenotype and compensatory elevation of oxidative phosphorylation (OXPHOS). TOMM34, a translocase of the outer mitochondrial membrane, was upregulated to promote tumor metastasis in response to metformin-induced metabolic stress.

Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/β-catenin signaling to promote colorectal cancer progression by preventing mA-mediated degradation of STEAP3 mRNA.

Background: Hypoxia, a typical hallmark of solid tumors, exhibits an essential role in the progression of colorectal cancer (CRC), in which the dysregulation of long non-coding RNAs (lncRNAs) is frequently observed. However, the underlying mechanisms are not clearly defined.

Methods: The TCGA database was analyzed to identify differential lncRNA expression involved in hypoxia-induced CRC progression.

Association of recurrent APOBEC3B alterations with the prognosis of gastric-type cervical adenocarcinoma.

Objective: Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive type of endocervical adenocarcinoma (ECA) with distinct histopathologic features and unfavorable treatment outcomes, but no genomic prognostic factor has been revealed. We aimed to systematically investigate the somatic alterations of GCA at genome-wide level and evaluate their prognostic value.

Methods: We performed whole-exome sequencing (WES) on 25 pairs of tumor and matched normal samples to characterize the genomic features of Chinese patients with GCA and investigated their relations to histopathological characterizations and prognosis.

Inhibition of NPC1L1 disrupts adaptive responses of drug-tolerant persister cells to chemotherapy.

Entering a drug-tolerant persister (DTP) state of cancer cells is a transient self-adaptive mechanism by which a residual cell subpopulation accelerates tumor progression. Here, we identified the acquisition of a DTP phenotype in multidrug-resistant (MDR) cancer cells as a tolerance response to routine combination treatment. Characterization of MDR cancer cells with a DTP state by RNA-seq revealed that these cells partially prevented chemotherapy-triggered oxidative stress by promoting NPC1L1-regulated uptake of vitamin E.

PHLDB2 Mediates Cetuximab Resistance via Interacting With EGFR in Latent Metastasis of Colorectal Cancer.

Background & Aims: Latent metastasis of colorectal cancer (CRC) frequently develops months or years after primary surgery, followed by adjuvant therapies, and may progress rapidly even with targeted therapy administered, but the underlying mechanism remains unclear. Here, we aim to explore the molecular basis for the aggressive behavior of latent metastasis in CRC.

Methods: Transcriptional profiling and pathway enrichment analysis of paired primary and metastatic tumor samples were performed.