Direct Identification of O─O Bond Formation Through Three-Step Oxidation During Water Splitting by Operando Soft X-ray Absorption Spectroscopy.

Anionic redox allows the direct formation of O─O bonds from lattice oxygens and provides higher catalytic in the oxygen evolution reaction (OER) than does the conventional metal ion mechanism. While previous theories have predicted and experiments have suggested the possible O─O bond, it has not yet been directly observed in the OER process. In this study, operando soft X-ray absorption spectroscopy (sXAS) at the O K-edge and the operando Raman spectra is performed on layered double CoFe hydroxides (LDHs) after intercalation with [Cr(C2O4)3]3-, and revealed a three-step oxidation process, staring from Co2+ to Co3+, further to Co4+ (3d6L), and ultimately leading to the formation of O─O bonds and O2 evolution above a threshold voltage (1.4 V). In contrast, a gradual oxidation of Fe is observed in CoFe LDHs. The OER activity exhibits a significant enhancement, with the overpotential decreasing from 300 to 248 mV at 10 mA cm-2, following the intercalation of [Cr(C2O4)3]3- into CoFe LDHs, underscoring a crucial role of anionic redox in facilitating water splitting.

Neutrophil-like Monocytes Increase in Patients with Colon Cancer and Induce Dysfunctional TIGIT+ NK Cells.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of immune cells including granulocytic (CD14neg/CD15+/HLA-DRneg) and monocytic subtypes (CD14+/CD15neg/HLA-DRneg). In the present study, we found a population of monocytes expressing the granulocyte marker CD15 that significantly increased in both peripheral blood (PB) and tumoral tissues of patients with colorectal cancer (CRC). Further phenotypical analysis confirmed the granulocytic-like features of this monocyte subpopulation that is associated with an increase in granulocyte-monocyte precursors (GMPs) in the PB of these patients (pts). Mechanistically, this granulocyte-like monocyte population suppressed NK cell activity by inducing TIGIT and engaging NKp30. Accordingly, an increased frequency of TIGIT+ NK cells with impaired functions was found in both the PB and tumoral tissue of CRC pts. Collectively, we provided new mechanistic explanations for tumor immune escape occurring in CRC by showing the increase in this new kind of MDSC, in both PB and CRC tissue, which is able to significantly impair the effector functions of NK cells, thereby representing a potential therapeutic target for cancer immunotherapy.

A nomogram for predicting colorectal cancer liver metastasis using circulating tumor cells from the first drainage vein.

PURPOSE: To use circulating tumor cells (CTC) from the first drainage vein (FDV) of the primary lesion and other clinically relevant parameters to construct a nomogram for predicting liver metastasis in colorectal cancer (CRC) patients, and to provide a theoretical basis for clinical diagnosis and treatment. METHODS: Information from 343 CRC patients was collected and a database was established. Multivariate logistic analysis was used to identify independent factors for colorectal cancer liver metastasis(mCRC) and nomograms were constructed. Receiver operating characteristic curves(ROC), calibration plots, and decision curve analysis (DCA) were used to assess discrimination, agreement with actual risk, and the clinical utility of the prediction model, respectively. RESULT: CTC levels in FDV were significantly higher in patients with liver metastasis than in those without liver metastasis. Logistic multivariate analysis showed that vascular invasion, T stage, carcinoembryonic antigen (CEA), CA19-9, and CTC could be used as predictors to construct nomograms. The nomograms showed good discriminatory ability in predicting mCRC, with area under the curve (AUC) values of 0.871 [95 % CI: 0.817-0.924) and 0.891 (95 % CI: 0.817-0.964) for the training and validation sets, respectively.] The calibration curves of both the training and validation sets showed that the model was effective in predicting the probability of mCRC. DCA was used to evaluate this predictive model and showed good net clinical benefit. CONCLUSION: We developed and validated a nomogram model based on the combination of CTC in the FDV with other clinical parameters to better predict the occurrence of mCRC.

Unraveling the ncRNA landscape that governs colorectal cancer: A roadmap to personalized therapeutics.

Colorectal cancer (CRC) being one of the most common malignancies, has a significant death rate, especially when detected at an advanced stage. In most cases, the fundamental aetiology of CRC remains unclear despite the identification of several environmental and intrinsic risk factors. Numerous investigations, particularly in the last ten years, have indicated the involvement of epigenetic variables in this type of cancer. The development, progression, and metastasis of CRC are influenced by long non-coding RNAs (lncRNAs), which are significant players in the epigenetic pathways. LncRNAs are implicated in diverse pathological processes in CRC, such as liver metastasis, epithelial to mesenchymal transition (EMT), inflammation, and chemo-/radioresistance. It has recently been determined that CRC cells and tissues exhibit dysregulation of tens of oncogenic and tumor suppressor lncRNAs. Serum samples from CRC patients exhibit dysregulated expressions of several of these transcripts, offering a non-invasive method of detecting this kind of cancer. In this review, we outlined the typical paradigms of the deregulated lncRNA which exert significant role in the underlying molecular mechanisms of CRC initiation and progression. We comprehensively discuss the role of lncRNAs as innovative targets for CRC prognosis and treatment.

PDPN/CCL2/STAT3 feedback loop alter CAF heterogeneity to promote angiogenesis in colorectal cancer.

Colorectal cancer (CRC) is one of the common clinical malignancies and the fourth leading cause of cancer-related death in the world. The tumor microenvironment (TME) plays a crucial role in promoting tumor angiogenesis, and cancer-associated fibroblasts (CAFs) are one of the key components of the tumor microenvironment. However, due to the high heterogeneity of CAFs, elucidating the molecular mechanism of CAF-mediated tumor angiogenesis remained elusive. In our study, we found that there is pro-angiogenic functional heterogeneity of CAFs in colorectal cancer and we clarified that Podoplanin (PDPN) can specifically label CAF subpopulations with pro-angiogenic functions. We also revealed that PDPN + CAF could maintain CAF heterogeneity by forming a PDPN/CCL2/STAT3 feedback loop through autocrine CCL2, while activate STAT3 signaling pathway in endothelial cells to promote angiogenesis through paracrine CCL2. We demonstrated WP1066 could inhibit colorectal cancer angiogenesis by blocking both the PDPN/CCL2/STAT3 feedback loop in CAFs and the STAT3 signaling pathway in endothelial cells. Altogether, our study suggests that STAT3 could be a potential therapeutic target for blocking angiogenesis in colorectal cancer. We provide theoretical basis and new therapeutic strategies for the clinical treatment of colorectal cancer.

SIPA1 promotes epithelial-mesenchymal transition in colorectal cancer through STAT3 activation.

Colorectal cancer (CRC) is the third leading cancer type worldwide and accounts for the second highest rate of cancer-related mortality. Liver metastasis significantly contributes to the mortality associated with CRC, but the fundamental mechanisms behind it remain unclear. Signal-induced proliferation-associated protein 1 (SIPA1), a GTPase activating protein, has been shown to promote metastasis in breast cancer. In this study, our objective was to explore the role of SIPA1 in regulating epithelial-mesenchymal transition (EMT) in CRC. The analysis of The Cancer Genome Atlas (TCGA) database revealed that the expression level of SIPA1 mRNA was notably upregulated and exhibited a positively correlated with EMT and STAT3 signaling pathways in CRC. Knockdown of SIPA1 impairs CRC cell proliferation and migration. Further studies on the reliance of SIPA1 on STAT3 signaling for EMT regulation have shown that SIPA1 stimulates the activation of STAT3, resulting in its nuclear translocation. The co-treatment of overexpressed SIPA1 with the STAT3 inhibitor STTITA has shown that SIPA1 regulates the expression of EMT-related markers through STAT3. Our study indicate that SIPA1 promotes CRC metastasis by activating the STAT3 signaling pathway, underscoring the potential of SIPA1 as a therapeutic target for metastatic CRC patients.

The Role of Dietary Vitamins and Antioxidants in Preventing Colorectal Cancer: A Systematic Review.

The role of dietary vitamins and antioxidants in preventing colorectal cancer (CRC) is a significant area of research within nutritional oncology. However, the relationship between these nutrients and CRC prevention is complex and influenced by factors such as dosage, timing, and individual health status. This review aims to comprehensively analyze and synthesize the existing scientific literature on the potential role of dietary vitamins and antioxidants in preventing CRC. A comprehensive literature review was conducted by searching electronic databases to identify studies examining the prospected impacts of dietary vitamins and antioxidants on the prevention of CRC. According to the outcomes of this review, this research review shows a complex link between vitamins and CRC. While some vitamins such as B2, B6, and D seemed helpful, others such as A and E had mixed results. Vitamin C deficiency was even linked to worse outcomes in cancer patients. Overall, the studies suggest focusing on a balanced diet rich in various vitamins rather than relying solely on individual supplements to prevent CRC. On the other hand, the results of our review suggest that the relationship between antioxidant intake and CRC is more intricate than previously thought. Data from this review indicates that taking specific antioxidant supplements such as selenium and vitamin E does not seem to offer the same protection. This suggests that a balanced diet with a variety of antioxidants is more helpful than focusing on single supplements. While we did not observe a direct association, future studies could investigate how different types and combinations of antioxidants might influence CRC development. In conclusion, the present systematic review highlights the need for more research on the relationship between vitamins, antioxidants, and CRC. We need to understand how these nutrients affect both the survival of people with CRC and the prevention of the disease. This will help us determine the best ways to use vitamins and antioxidants in CRC management and prevention.

Preliminary study on the active substances and cellular pathways of lactic acid bacteria for colorectal cancer treatment.

Colorectal cancer (CRC) is a common malignant tumor and is one of the three most common cancers worldwide. Traditional surgical treatment, supplemented by chemotherapy and radiotherapy, has obvious side effects on patients. Immunotherapy may lead to some unpredictable complications. Low introduction rate and high cost are some of the problems of gene therapy, so finding a safe, reliable and least toxic treatment method became the main research direction for this study. Lactic acid bacteria and their metabolites are widely used in functional foods or as adjuvant therapies for various diseases because they are safe to eat and have no adverse reactions. Research has shown that lactic acid bacteria and their metabolites play an auxiliary therapeutic role in colorectal cancer mainly by improving the intestinal flora composition, inhibiting the growth of pathogenic bacteria and inhibiting the proliferation of cancer cells. It is now widely believed that the substances that probiotics such as lactic acid bacteria exert anti-cancer effects are mainly secondary metabolites such as butyric acid. Lb. plantarum AY01 isolated from fermented food has good anti-cancer ability, and its main anti-cancer substance is 2'-deoxyinosine. Through flow cytometry detection, it was found that Lb. plantarum AY01 can block cell proliferation in the S phase. In addition, Lb. plantarum AY01 culture reduces the sensitivity of mice to colitis-associated CRC induced by azoxymethane (AOM)/dextran sulfate sodium salt (DSS) and exhibits the occurrence and promotion of tumors. According to transcriptome analysis, Lb. plantarum AY01 may induce apoptosis of colorectal cancer cells by activating the p38 MAPK pathway. This experiment provided possibilities for the treatment of CRC.

Prognostic role of immunohistochemical PTEN (phosphatase and tensin homolog) expression and PTEN (rs701848) genotypes among Egyptian patients with different stages of colorectal cancer.

Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second major cause of cancer-related death. Thus, we attempted to ascertain the relationship between the genotype and allele frequencies of phosphatase and tensin homolog (PTEN) and immunohistochemical PTEN expression with clinicopathological characteristics in patients with CRC. 150 individuals were allocated into two groups for this cross-sectional randomized case-control study: Group I consisted of 100 patients with histopathologically proven CRC of various stages. Group II: Fifty healthy volunteers. Genetic analysis of PTEN (rs701848 T / C) single nucleotide polymorphism (SNP) was performed using TaqManTM assays and real-time PCR, while PTEN expressions were assessed using immunohistochemical staining. PTN SNP genotypes and alleles did not significantly differ between CRC patients and controls. PTEN expression was lost in 28% of CRC patients, while all healthy controls exhibited PTEN expression. Negative PTEN expression was present in 16 (80%) of stage IV CRC cases, 9 (23.7%) of stage III cases, 3 (37.5%) of stage II cases, and none of stage I cases. It was shown that PTEN expression was weakly positive, moderately positive, and strongly positive in 15, 10, and 9 (respectively) cases of CRC stage I. However, the expression was only weekly positive in 4 (20%) of the patients in stage IV. In the stage IV group, neither moderately nor strongly positive PTEN expressions were found. So, Among Egyptians, the emergence or course of colorectal cancer is unrelated to the PTEN gene mutation. However, the formation and progression of CRC may be influenced by weak or lost PTEN expression.

Porphyromonas gingivalis fuels colorectal cancer through CHI3L1-mediated iNKT cell-driven immune evasion.

The interaction between the gut microbiota and invariant Natural Killer T (iNKT) cells plays a pivotal role in colorectal cancer (CRC). The pathobiont Fusobacterium nucleatum influences the anti-tumor functions of CRC-infiltrating iNKT cells. However, the impact of other bacteria associated with CRC, like Porphyromonas gingivalis, on their activation status remains unexplored. In this study, we demonstrate that mucosa-associated P. gingivalis induces a protumour phenotype in iNKT cells, subsequently influencing the composition of mononuclear-phagocyte cells within the tumor microenvironment. Mechanistically, in vivo and in vitro experiments showed that P. gingivalis reduces the cytotoxic functions of iNKT cells, hampering the iNKT cell lytic machinery through increased expression of chitinase 3-like-1 protein (CHI3L1). Neutralization of CHI3L1 effectively restores iNKT cell cytotoxic functions suggesting a therapeutic potential to reactivate iNKT cell-mediated antitumour immunity. In conclusion, our data demonstrate how P. gingivalis accelerates CRC progression by inducing the upregulation of CHI3L1 in iNKT cells, thus impairing their cytotoxic functions and promoting host tumor immune evasion.

Combinatorial control of Pseudomonas aeruginosa biofilm development by quorum-sensing and nutrient-sensing regulators.

The human pathogen Pseudomonas aeruginosa, a leading cause of hospital-acquired infections, inhabits and forms sessile antibiotic-resistant communities called biofilms in a wide range of biotic and abiotic environments. In this study, we examined how two global sensory signaling pathways-the RhlR quorum-sensing system and the CbrA/CbrB nutritional adaptation system-intersect to control biofilm development. Previous work has shown that individually these two systems repress biofilm formation. Here, we used biofilm analyses, RNA-seq, and reporter assays to explore the combined effect of information flow through RhlR and CbrA on biofilm development. We find that the ΔrhlRΔcbrA double mutant exhibits a biofilm morphology and an associated transcriptional response distinct from wildtype and the parent ΔrhlR and ΔcbrA mutants indicating codominance of each signaling pathway. The ΔrhlRΔcbrA mutant gains suppressor mutations that allow biofilm expansion; these mutations map to the crc gene resulting in loss of function of the carbon catabolite repression protein Crc. Furthermore, the combined absence of RhlR and CbrA leads to a drastic reduction in the abundance of the Crc antagonist small RNA CrcZ. Thus, CrcZ acts as the molecular convergence point for quorum- and nutrient-sensing cues. We find that in the absence of antagonism by CrcZ, Crc promotes the expression of biofilm matrix components-Pel exopolysaccharide, and CupB and CupC fimbriae. Therefore, this study uncovers a regulatory link between nutritional adaption and quorum sensing with potential implications for anti-biofilm targeting strategies.IMPORTANCEBacteria often form multicellular communities encased in an extracytoplasmic matrix called biofilms. Biofilm development is controlled by various environmental stimuli that are decoded and converted into appropriate cellular responses. To understand how information from two distinct stimuli is integrated, we used biofilm formation in the human pathogen Pseudomonas aeruginosa as a model and studied the intersection of two global sensory signaling pathways-quorum sensing and nutritional adaptation. Global transcriptomics on biofilm cells and reporter assays suggest parallel regulation of biofilms by each pathway that converges on the abundance of a small RNA antagonist of the carbon catabolite repression protein, Crc. We find a new role of Crc as it modulates the expression of biofilm matrix components in response to the environment. These results expand our understanding of the genetic regulatory strategies that allow P. aeruginosa to successfully develop biofilm communities.

Prognostic Value of Insulin Growth Factor-Like Receptor 1 (IGFLR1) in Stage II and III Colorectal Cancer and Its Association with Immune Cell Infiltration.

IGFLR1 is a novel biomarker, and some evidences suggested that is involved in the immune microenvironment of CRC. Here, we explored the expression of IGFLR1 and its association with the prognosis as well as immune cell infiltration in CRC, with the aim to provide a basis for further studies on IGFLR1. Immunohistochemical staining for IGFLR1, TIM-3, FOXP3, CD4, CD8, and PD-1 was performed in eligible tissues to analyze the expression of IGFLR1 and its association with prognosis and immune cell infiltration. Then, we screened colon cancer samples from TCGA and grouped patients according to IGFLR1-related genes. We also evaluated the co-expression and immune-related pathways of IGFLR1 to identify the potential mechanism of it in CRC. When P < 0.05, the results were considered statistically significant. IGFLR1 and IGFLR1-related genes were associated with the prognosis and immune cell infiltration (P < 0.05). In stage II and III CRC tissue and normal tissue, we found (1) IGFLR1 was expressed in both the cell membrane and cytoplasm and which was differentially expressed between cancer tissue and normal tissue. IGFLR1 expression was associated with the expression of FOXP3, CD8, and gender but was not associated with microsatellite instability. (2) IGFLR1 was an independent prognostic factor and patients with high IGFLR1 had a better prognosis. (3) A model including IGFLR1, FOXP3, PD-1, and CD4 showed good prognostic stratification ability. (4) There was a significant interaction between IGFLR1 and GATA3, and IGFLR1 had a significant co-expression with related factors in the INFR pathway. IGFLR1 has emerged as a new molecule related to disease prognosis and immune cell infiltration in CRC patients and showed a good ability to predict the prognosis of patients.

An Unusual Tumor: Squamous Cell Carcinoma of the Colon in Lynch Syndrome.

Primary squamous cell carcinoma of the colon and rectum is a rare malignancy. Most of the anatomical sites that are reported to be affected include the esophagus and anal canal. This report highlights the case of a 54-year-old male with a known history of Lynch syndrome and a previous diagnosis of colon cancer who was found to have a recurrence of malignancy affecting this unlikely area. The treatment strategies for this colorectal squamous cell carcinoma have not been thoroughly explored, so this report aims to highlight effective interventions, including surgical resection and neoadjuvant chemotherapy and radiation. There is a poor prognosis associated with this condition, as it does not typically present until the late stages; however, in this particular instance, early detection leads to improved outcomes.

DNA Methylation Biomarkers in Stool Samples: Enhancing Colorectal Cancer Screening Strategies.

Colorectal cancer (CRC) is a significant global health challenge, ranking among the leading causes of cancer-related mortality worldwide. Despite efforts in prevention and early detection, CRC incidence and mortality rates are expected to rise substantially. Traditional screening methods like gFOBT, FIT, flexible sigmoidoscopy, colonoscopy, CTC, and colon capsule have limitations, including false positives/negatives, limited scope, or invasiveness. Recent developments in CRC screening involve DNA methylation biomarkers, showing promise in detecting early-stage CRC and precancerous lesions. Stool-based DNA testing is emerging as a noninvasive and convenient method for detecting CRC-associated DNA methylation alterations, offering potential for earlier detection compared to traditional methods. Several commercial stool-based DNA methylation tests targeting different genes associated with CRC have demonstrated varying sensitivity and specificity, some surpassing traditional screening methods. Challenges remain in optimizing their performance and accessibility. This review discusses how DNA methylation biomarkers could enhance CRC screening, and stool-based DNA methylation tests could revolutionize CRC screening practices, comparing them to the gold standard.

Single nucleotide polymorphisms in SEPALLATA 2 underlie fruit length variation in cucurbits.

Complete disruption of critical genes is generally accompanied by severe growth and developmental defects, which dramatically hinder its utilization in crop breeding. Identifying subtle changes, such as single nucleotide polymorphisms (SNPs), in critical genes that specifically modulate a favorable trait is a prerequisite to fulfill breeding potential. Here, we found two SNPs in the E-class floral organ identity gene cucumber (Cucumis sativus) SEPALLATA2 (CsSEP2) that specifically regulate fruit length. Haplotype (HAP) 1 (8G2667A) and HAP2 (8G2667T) exist in natural populations, whereas HAP3 (8A2667T) is induced by ethyl methanesulfonate mutagenesis. Phenotypic characterization of four near-isogenic lines and a mutant line showed that HAP2 fruits are significantly longer than those of HAP1, and those of HAP3 are 37.8% longer than HAP2 fruit. The increasing fruit length in HAP1-3 was caused by a decreasing inhibitory effect on CRABS CLAW (CsCRC) transcription (a reported positive regulator of fruit length), resultinged in enhanced cell expansion. Moreover, a 7638G/A-SNP in melon (Cucumis melo) CmSEP2 modulates fruit length in a natural melon population via the conserved SEP2-CRC module. Our findings provide a strategy for utilizing essential regulators with pleiotropic effects during crop breeding.

The roles of lncRNA AP001469.3 in clinical implications, immune landscape and carcinogenesis of colorectal cancer.

Background: Previously, long non-coding RNA (lncRNA) gene AP001469.3 was reported to participate in the construction of an immune-related lncRNA signature, which showed promising clinical predictive value in colorectal cancer (CRC) patients. However, the clinical and immunological significance and biological function of AP001469.3 in CRC remain unclear. In this study, we aim to explore the roles of AP001469.3 in CRC progression, thereby opening an avenue for CRC treatment. Methods: Our study collected data from The Cancer Genome Atlas (TCGA) database and investigated the role of AP001469.3 in CRC through bioinformatics analysis. Cell-type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) methods evaluated the immune infiltration. The biological functions of AP001469.3 in CRC were validated by in vitro experiments. Gene set enrichment analysis (GSEA) was used to estimate the enrichment of functional pathways and gene signatures. Results: In this work, high expression of AP001469.3 was found in CRC and was positively associated with tumor-node-metastasis (TNM) stage in CRC. AP001469.3 expression had a strong relationship with microsatellite instability (MSI) in colon adenocarcinoma (COAD). Additionally, AP001469.3 expression was associated with StromalScore, ImmuneScore, ESTIMATEScore, immune cell infiltration (ICI) levels and immune checkpoint (ICP) genes expression in CRC. Subsequent results showed that immunotherapy could be more effective in CRC patients with low-AP001469.3 expression using the immunophenoscore (IPS). We confirmed that the transcript of AP001469.3 gene ENST00000430259 was highly expressed in CRC tissues and cell lines. In vitro experiments indicated that ENST00000430259 knockdown reduced the proliferation, migration and invasion of CRC cells. Finally, our GSEA results showed that the majority of the differentially enriched signaling pathways between the high- and low-AP001469.3 expression groups were immune-related. Conclusions: Taken together, our study demonstrates that lncRNA gene AP001469.3 is associated with immunological characteristics in CRC and promotes malignant progression of CRC. Moreover, AP001469.3 can be potentially used as an immunotherapeutic indicator and a therapeutic target for CRC patients.

SLC12A8 upregulation promotes colorectal cancer progression and chemoresistance.

Background: Colorectal cancer (CRC), a prevalent gastrointestinal malignant disease, causes substantial morbidity and mortality. Identification of novel prognostic biomarkers and therapeutic targets is critically needed to improve patient outcomes. Although solute carrier family 12 member 8 (SLC12A8) has high expression in various tumors and affects tumor progression, its role in CRC remains unclear. The aim of this study was to investigate the functions of SLC12A8 in CRC. Methods: SLC12A8 expression and its association with clinical significance in CRC patients were explored via multiple public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), The Human Protein Atlas (HPA), The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), and Kaplan-Meier plotter. The effects of SLC12A8 on the CRC cell apoptosis, epithelial-mesenchymal transition (EMT), reactive oxygen species (ROS) production, and sensitivity to oxaliplatin were verified by in vitro experiments. Results: SLC12A8 expression was upregulated in CRC tissues compared with normal colorectal tissues. Furthermore, high expression of SLC12A8 was associated with poorer prognosis in CRC patients. Pathway enrichment analyses revealed SLC12A8 involvement in oxidative stress and transforming growth factor-beta (TGF-ß) signaling. Experiments in CRC cells showed that SLC12A8 upregulation promoted apoptosis resistance, EMT, and inhibited ROS production. Moreover, SLC12A8 knockdown enhanced the sensitivity of CRC cells to oxaliplatin chemotherapy. Conclusions: Our integrative analyses identify SLC12A8 as a candidate biomarker for CRC progression. Targeting SLC12A8 may improve patient responses to oxaliplatin-based treatment regimens.

Telomere-related gene risk model for prognosis prediction in colorectal cancer.

Background: Colorectal cancer (CRC) is the third-most prevalent cancer globally. The biological significance of telomeres in CRC carcinogenesis and progression is underscored by accumulating data. Nevertheless, not much is known about how telomere-related genes (TRGs) affect CRC prognosis. Therefore, the aim of this study was to investigate the role of TRGs in CRC prognosis. Methods: We retrospectively obtained the expression profiles and clinical data of CRC patients from public databases. Utilizing least absolute shrinkage and selection operator (LASSO) regression analysis, we created a telomere-related risk model to predict survival outcomes, identifying ten telomere-related differentially expressed genes (TRDEGs). Based on TRDEGs, we stratified patients from The Cancer Genome Atlas (TCGA) into low- and high-risk subsets. Subsequently, we conducted comprehensive analyses, including survival assessment, immune cell infiltration, drug sensitivity, and prediction of molecular interactions using Kaplan-Meier curves, ESTIMATE, CIBERSORT, OncoPredict, and other approaches. Results: The model showed exceptional predictive accuracy for survival. Significant differences in survival were observed between the two groups of participants grouped according to the model (P<0.001), and this difference was further confirmed in the external validation set (GSE39582) (P=0.004). Additionally, compared to the low-risk group, the high-risk group exhibited significantly advanced tumor node metastasis (TNM) stages, lower proportions of activated CD4+ T cells, effector memory CD4+ T cells, and memory B cells, but increased ratios of M2 macrophages and regulatory T cells (Tregs), elevated tumor immune dysfunction and exclusion (TIDE) scores, and diminished sensitivity to dabrafenib, lapatinib, camptothecin, docetaxel, and telomerase inhibitor IX, reflecting the signature's capacity to distinguish clinical pathological characteristics, immune environment, and drug efficacy. Finally, we validated the expression of the ten TRDEGs (ACACB, TPX2, SRPX, PPARGC1A, CD36, MMP3, NAT2, MMP10, HIGD1A, and MMP1) through quantitative real-time polymerase chain reaction (qRT-PCR) and found that compared to normal cells, the expression levels of ACACB, HIGD1A, NAT2, PPARGC1A, and TPX2 in CRC cells were elevated, whereas those of CD36, SRPX, MMP1, MMP3, and MMP10 were reduced. Conclusions: Overall, we constructed a telomere-related biomarker capable of predicting prognosis and treatment response in CRC individuals, offering potential guidance for drug therapy selection and prognosis prediction.