Colorectal Cancer Patients Research Articles

Size Matters: Curvature and Antigen-Mediated Dual Recognition of Size-Specific Tumor-Derived Exosomes.

Accurate identification of tumor-derived exosomes is crucial for advancing cancer diagnosis and therapies. However, distinguishing tumor-derived exosomes is challenging due to the heterogeneity of exosomes, which reflect different sizes and cells of origin. To address this challenge, we introduce the curvature and antigen-mediated proximity ligation assay for tumor-derived exosomes (CAPTURE) strategy, which leverages the size-selective properties of curvature-sensing peptides and specific antigen binding of aptamers. CAPTURE enables highly specific identification and precise quantification of the PD-L1+ exosomes in plasma samples. CAPTURE is proven to be simple, homogeneous, rapid, and highly selective, achieving a 100% specificity in discriminating colorectal cancer (CRC) patients from healthy donors. Overall, the CAPTURE strategy presents a promising avenue for precise and noninvasive cancer diagnosis.

ALYREF recruits ELAVL1 to promote colorectal tumorigenesis via facilitating RNA m5C recognition and nuclear export

ALYREF can recognize 5-methylcytosine (m5C) decoration throughout RNAs to regulate RNA metabolism. However, its implications in cancer and precise regulatory mechanisms remain largely elusive. Here, we demonstrated that ALYREF supported colorectal cancer (CRC) growth and migration. Integrated analysis of ALYREF-RIP-Bis-seq and transcriptome profiles identified ribosomal protein S6 kinase B2 (RPS6KB2) and regulatory-associated protein of mTOR (RPTOR) as ALYREF’s possible downstream effectors. Mechanistically, ALYREF formed a complex with ELAV like RNA binding protein 1 (ELAVL1) to cooperatively promote m5C recognition and nuclear export of the two mRNAs. Moreover, ALYREF protein was highly expressed in tumor tissues of CRC patients, which predicted their poor prognosis. E2F transcription factor 6 (E2F6)-mediated transactivation gave a molecular insight into ALYREF overexpression. Collectively, ALYREF recruits ELAVL1 to collaboratively facilitate m5C recognition and nuclear export of RPS6KB2 and RPTOR transcripts for colorectal tumorigenesis, providing RNA m5C methylation as promising therapeutic targets and prognostic biomarkers for CRC.

Evaluation of Circulating Tumor DNA and Carcinoembryonic Antigen Levels and Relationship with Clinicopathological Risk Factors and Prognostic Indices in Colorectal Cancer Patients

Objective: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. ctDNA has emerged as a promising biomarker for CRC management, offering real-time insights into tumor burden and genetic mutations. This study investigates the correlation between CEA levels, ctDNA, clinicopathological factors, and treatment outcomes in early and advanced CRC patients. Methods: The study retrospectively analyzed data from CRC patients, including early-stage disease and metastatic disease. ctDNA levels, demographic data, and clinical parameters such as CEA, inflammatory indexes, and tumor characteristics were evaluated to determine correlations with treatment outcomes. Results: The study included 20 patients, with 60% diagnosed at the metastatic stage. The study found no statistically significant correlation between ctDNA levels and disease stage, recurrence, or overall survival. While CEA and ctDNA levels were measured, they did not demonstrate a significant relationship with treatment outcomes. Notably, ctDNA levels were higher in metastatic patients, though this was not statistically significant. Conclusion: Despite its potential, the integration of ctDNA as a routine biomarker in CRC care faces challenges, including variability in measurement techniques and cost-effectiveness. However, ctDNA's ability to guide personalized treatment strategies and monitor disease recurrence holds promise. The study's findings align with previous research, suggesting ctDNA as a poor prognostic indicator, though further research is needed. ctDNA represents a significant advance in CRC management, offering non-invasive, real-time insights into tumor dynamics. Ongoing research is expected to solidify its role in personalized treatment planning, potentially leading to more effective and tailored therapies for CRC patients.

A multidimensional recommendation framework for identifying biological targets to aid the diagnosis and treatment of liver metastasis in patients with colorectal cancer

The quest to understand the molecular mechanisms of tumour metastasis and identify pivotal biomarkers for cancer therapy is increasing in importance. Single-omics analyses, constrained by their focus on a single biological layer, cannot fully elucidate the complexities of tumour molecular profiles and can thus overlook crucial molecular targets. In response to this limitation, we developed a multiobjective recommendation system (RJH-Metastasis 1.0) anchored in a multiomics knowledge graph to integrate genome, transcriptome, and proteome data and corroborative literature evidence and then conducted comprehensive analyses of colorectal cancer with liver metastasis (CRCLM). A total of 25 key genes significantly associated with CRCLM were recommended by our system, and GNB1, GATAD2A, GBP2, MACROD1, and EIF5B were further highlighted. Specifically, GNB1 presented fewer mutations but elevated RNA transcription and protein expression in CRCLM patients. The role of GNB1 in promoting the malignant behaviours of colon cancer cells was demonstrated via in vitro and in vivo studies. Aberrant expression of GNB1 could be regulated by METTL1-driven m7G modification. METTL1 knockdown decreased m7G modification in the 3’ UTR of GNB1, increasing its mRNA transcription and translation during liver metastasis. Furthermore, GNB1 induced the formation of an immunosuppressive microenvironment by promoting the CLEC2C-KLRB1 interaction between memory B cells and KLRB1+PD-1+CD8+ cells. GNB1 expression and the efficacy of PD-1 antibody-based treatment in CRCLM patients were significantly correlated. In summary, our recommendation system can be used for effective exploration of key molecules in colorectal cancer, among which GNB1 was identified as a critical CRCLM promoter and immunotherapy biomarker in colorectal cancer patients.

Phase II Study of Irinotecan, Trifluridine/tipiracil (TAS-102) plus Bevacizumab as a Later-line Therapy for Patients with Metastatic Colorectal Cancer (mCRC): a prospective single-center explorative study.

To explore the efficacy and safety of the combination of irinotecan, trifluridine/tipiracil (TAS-102), and bevacizumab in a later-line setting for metastatic colorectal cancer (mCRC) patients. This was a single-center, phase II trial. The mCRC patients who are refractory to standard first-line and second-line treatment are eligible. Patients who previously received irinotecan while progressing during maintenance therapy are also eligible. The primary endpoint was the objective response rate (ORR). Between August 1, 2022, and September 30, 2023, 35 patients were enrolled, and 31 of them were evaluable for efficacy. The ORR was 25.8% (8/31), and the disease control rate (DCR) was 93.5% (29/31). As of April 30, 2024, the median progression-free survival (PFS) was 9.2 months (95% CI 6.285-12.115), whereas the median overall survival (OS) was not reached with the 1-year OS rate of 73.5%. The most common grade 3/4 treatment-related adverse events were neutropenia (34.3%), anemia (17.1%), and thrombocytopenia (8.6%). Irinotecan, TAS-102 plus bevacizumab regimen preliminarily demonstrated promising efficacy with tolerable toxicity for mCRC patients as later-line treatment. This regimen warrants further exploration in refractory mCRC patients.

Systematic analysis of human colorectal cancer scRNA-seq revealed limited pro-tumoral IL-17 production potential in gamma delta T cells

Gamma delta T cells play a crucial role in anti-tumor immunity due to their cytotoxic properties. However, the role and extent of γδ T cells in production of pro-tumorigenic interleukin-17 (IL-17) within the tumor microenvironment of colorectal cancer (CRC) remains controversial. In this study, we re-analyzed nine published human CRC whole-tissue single-cell RNA sequencing datasets, identifying 18,483 γδ T cells out of 951,785 total cells, in the neoplastic or adjacent normal tissue of 165 human CRC patients. Our results confirm that tumor-infiltrating γδ T cells exhibit high cytotoxicity-related transcription in both tumor and adjacent normal tissues, but critically, none of the γδ T cell clusters showed IL-17 production potential. We also identified various γδ T cell subsets, including poised effector-like T cells, tissue-resident memory T cells, progenitor exhausted-like T cells, and exhausted T cells, and noted an increased expression of cytotoxic molecules in tumor-infiltrating γδ T cells compared to their normal area counterparts. We proposed anti-tumor γδ T effector cells may arise from tissue-resident progenitor cells based on the trajectory analysis. Our work demonstrates that γδ T cells in CRC primarily function as cytotoxic effector cells rather than IL-17 producers, mitigating the concerns about their potential pro-tumorigenic roles in CRC, highlighting the importance of accurately characterizing these cells for cancer immunotherapy research and the unneglectable cross-species discrepancy between the mouse and human immune system in the study of cancer immunology.

Functional Three-Dimensional Zeolitic Imidazolate Framework with an Ordered Macroporous Structure for the Isolation of Extracellular Vesicles.

Extracellular vesicles (EVs) and their cargoes are increasingly being recognized as noninvasive diagnostic markers, necessitating the isolation of EVs from complex biological samples. Herein, a distearoyl phospholipid ethanolamine-functionalized single-crystal ordered macroporous three-dimensional zeolitic imidazolate framework (SOM-ZIF-8-DSPE) was developed, which combines the surface charge interaction of ZIF-8 with the synergistic effect of DSPE insertion into the phospholipid membrane of EVs to improve the isolating selectivity of EV capture. The materials have porous structures larger than 300 nm in diameter, providing enough space and active sites to trap EVs. Benefiting from this feature, the entire isolation process takes only 10 min and is well compatible with the subsequent analysis of RNA in EVs. Consequently, 10 upregulated miRNA of plasma EVs in the primary colorectal cancer (pCRC) patients is found over the healthy donors, and 6 upregulated miRNA of plasma EVs in the metastatic colorectal cancer (mCRC) patients over pCRC patients. These findings suggest that the isolation of EV-based SOM-ZIF-8-DSPE is a promising strategy to identify biomarkers for disease diagnosis, such as miRNAs in plasma EVs for the early detection of CRC.

In-Depth Proteomic Analysis of Paraffin-Embedded Tissue Samples from Colorectal Cancer Patients Revealed TXNDC17 and SLC8A1 as Key Proteins Associated with the Disease.

A deeper understanding of colorectal cancer (CRC) biology would help to identify specific early diagnostic markers. Here, we conducted quantitative proteomics on FFPE healthy, adenoma, and adenocarcinoma tissue samples from six stage I sporadic CRC patients to identify dysregulated proteins during early CRC development. Two independent quantitative 10-plex TMT experiments were separately performed. After protein extraction, trypsin digestion, and labeling, proteins were identified and quantified by using a Q Exactive mass spectrometer. A total of 2681 proteins were identified and quantified after data analysis and bioinformatics with MaxQuant and the R program. Among them, 284 and 280 proteins showed significant upregulation and downregulation (expression ratio ≥1.5 or ≤0.67, p-value ≤0.05), respectively, in adenoma and/or adenocarcinoma compared to healthy tissue. Ten dysregulated proteins were selected to study their role in CRC by WB, IHC, TMA, and ELISA using tissue and plasma samples from CRC patients, individuals with premalignant colorectal lesions (adenomas), and healthy individuals. In vitro loss-of-function cell-based assays and in vivo experiments using three CRC cell lines with different metastatic properties assessed the important roles of SLC8A1 and TXNDC17 in CRC and liver metastasis. Additionally, SLC8A1 and TXNDC17 protein levels in plasma possessed the diagnostic ability of early CRC stages.

USP10 drives cancer stemness and enables super-competitor signalling in colorectal cancer.

The contribution of deubiquitylating enzymes (DUBs) to β-Catenin stabilization in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, and by using an unbiassed screen, we discovered that the DUB USP10 stabilizes β-Catenin specifically in APC-truncated CRC in vitro and in vivo. Mechanistic studies, including in vitro binding together with computational modelling, revealed that USP10 binding to β-Catenin is mediated via the unstructured N-terminus of USP10 and is outcompeted by intact APC, favouring β-catenin degradation. However, in APC-truncated cancer cells USP10 binds to β-catenin, increasing its stability which is critical for maintaining an undifferentiated tumour identity. Elimination of USP10 reduces the expression of WNT and stem cell signatures and induces the expression of differentiation genes. Remarkably, silencing of USP10 in murine and patient-derived CRC organoids established that it is essential for NOTUM signalling and the APC super competitor-phenotype, reducing tumorigenic properties of APC-truncated CRC. These findings are clinically relevant as patient-derived organoids are highly dependent on USP10, and abundance of USP10 correlates with poorer prognosis of CRC patients. Our findings reveal, therefore, a role for USP10 in CRC cell identity, stemness, and tumorigenic growth by stabilising β-Catenin, leading to aberrant WNT signalling and degradation resistant tumours. Thus, USP10 emerges as a unique therapeutic target in APC truncated CRC.

LC-MS/MS analysis reveals plasma protein signatures associated with lymph node metastasis in colorectal cancer

ObjectivesColorectal cancer (CRC) is a major global health concern, ranking as the third most common cancer and the fourth leading cause of cancer-related deaths worldwide. Currently, the diagnostic accuracy of Lymph node metastasis (LNM) is currently unsatisfactory. Therefore, there is an urgent need to develop a reliable tool that can accurately predict lymph node metastasis (LNM) in patients diagnosed with CRC.MethodsWe conducted an extensive proteomics investigation aimed at examining lymph node metastasis (LNM) in individuals diagnosed with colorectal cancer (CRC). In the discovery stage, employing a mass spectrometry-based proteomic approach, we analyzed a cohort of 60 colorectal cancer patients (NM=30, LNM=30), identifying distinct molecular profiles that differentiate patients with and without lymph node metastasis (LNM). Subsequently, we validated the protein classifier associated with lymph node metastasis.ResultsWe elucidated a combinatorial predictive protein biomarker that can distinguish patients with and without lymph node metastasis by LC-MS/MS. The classifier achieved an area under the curve (AUC) of 0.892 (95% CI, 0.842-0.941), while in the testing cohort, it attained an AUC of 0.929 (95% CI, 0.824-1.000). Furthermore, the four protein markers demonstrated an AUC of 0.84 (95% CI, 0.783–0.890) in the validation cohort. Additionally, we categorized patients into three types based on immunophenotyping. Type 1 primarily consisted of patients with negative lymph node metastasis (NM), characterized by immune cells such as NK cells, CD4 T effector memory cells, and memory B cells. Type 2 mainly included patients with positive lymph node metastasis (LNM), characterized by immune cells such as mesangial cells, epithelial cells, and mononuclear cells. In Type 1, a prominent upregulation observed in immune inflammation, as well as in glucose and lipid metabolism. In Type 2, significant upregulation was evident in pathways such as pyrimidine metabolism and cell cycle regulation. The findings of this study suggest that immune mechanisms may exert a pivotal role in the process of lymph node metastasis in CRC.ConclusionsHere, we present plasma protein signatures associated with lymph node metastasis in colorectal cancer (CRC). However, further validation across multiple centers is necessary to generalize these findings.

The Debated Issue on Tissue Copper Levels in Colorectal Cancer Patients: A Meta-analysis and Replication Study.

Colorectal cancer (CRC) is a growing public health problem. Several clinical studies have shown a potentially oncogenic role of copper in CRC progression, but the reports are inconsistent. To examine published evidence on the association between tissue copper status and CRC, we carried out a systematic review and meta-analysis, searching Cochrane Library, EBSCOhost, Embase, ProQuest, PubMed/Medline, Scopus, and Web of Science for studies reporting colon tumor and matched non-cancerous tissue copper concentrations in CRC patients for articles published till June 2023. Based on a random effects model, standardized mean differences (SMD) were assessed. We also completed a replication study on 17 CRC patients that analyzed copper levels in both cancer tissue specimens and healthy mucosa dissected from the same patient. Thirteen studies investigating copper levels (including the replication study) in colorectal specimens from a pooled total of 312 CRC and 298 healthy mucosa were selected. Our meta-analysis estimated a high between-study heterogeneity (I2 = 96%) and lower levels of copper in CRC tissue cancer specimens than in matched healthy mucosa: the decrease was equal to - 0.74 (95% CI, - 2.18; 0.71) but was not significant. The replication study showed a significant decrease in tissue cancer specimens. Sensitivity analyses of the meta-analysis revealed that pre-analytical methodology for tissue preparation significantly reduced the between-study heterogeneity strongly influencing copper levels (p < 0.01), indicating a copper decrease in the cytoplasmic copper pool of the tumor tissue suggesting a rapid turnover of the metal in cancer cells.

Efficacy and Safety of Anti-EGFR Therapy Rechallenge in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.

Colorectal cancer (CRC) represents the second leading cause of cancer-related mortality worldwide, with a significant portion of patients presenting with metastatic disease at diagnosis. Resistance to initial anti-EGFR therapy, a key treatment for RAS wild-type metastatic CRC, remains a major challenge. This study aimed to assess the efficacy and safety of rechallenge with anti-EGFR therapy in patients with metastatic CRC who have progressed after prior treatments. A systematic search was conducted across PubMed, Web of Science, Cochrane, and Scopus. Studies were included if they were randomized controlled trials (RCTs) or observational studies involving patients with EGFR-mutated metastatic CRC who received anti-EGFR therapy as a rechallenge. Endpoints included objective response rate (ORR), disease control rate (DCR), and the incidence of adverse events. Statistical analyses were performed using the DerSimonian/Laird random effect model, with heterogeneity assessed via I2 statistics. R, version 4.2.3, was used for statistical analyses. Fourteen studies were included with 520 patients; 50.3% were male, and the median age was 63years old. The median progression-free survival (mPFS) ranged between 2.4 and 4.9months, while the median overall survival (mOS) ranged from 5 to 17.8months. Our pooled analysis demonstrated an objective response rate (ORR) of 17.70% (95% CI, 8.58-26.82%) and a disease control rate (DCR) of 61.72% (95% CI, 53.32-70.11%), both with significant heterogeneity (I2, 84% and 80%, respectively; p < 0.01). In the subgroup analysis, cetuximab showed an ORR of 18.31% (95% CI, 4.67-31.94%), and panitumumab an ORR of 10.9% (95% CI, 0.00-26.82%), while the combination of both resulted in an ORR of 29.24% (95% CI, 0.00-65.84%). For DCR, cetuximab resulted in 62.1% (95% CI, 49.32-74.87%), panitumumab in 63.05% (95% CI, 52.13-73.97%), and the combination in 60.34% (95% CI, 31.92-88.77%), all with significant heterogeneity. Adverse events included anemia (15.39%), diarrhea (4.20%), hypomagnesemia (6.40%), neutropenia (22.57%), and skin rash (13.22%). Rechallenge with anti-EGFR therapy in metastatic CRC patients shows moderate efficacy with manageable safety profiles. These findings highlight the need for careful patient selection and monitoring to optimize outcomes. Further studies are warranted to refine strategies for maximizing the therapeutic benefits of anti-EGFR rechallenge.

L-tryptophan and copper interactions linked to reduced colibactin genotoxicity in pks+ Escherichia coli.

Colibactin is a small molecule produced by pks+ Enterobacteriaceae that damages DNA, leading to oncogenic mutations in human genomes. Colibactin-producing Escherichia coli (pks+) cells promote tumorigenesis in mouse models of colorectal cancer (CRC) and are elevated in abundance in CRC patient biopsies, making it important to identify the regulatory systems governing colibactin production. Here, we apply a systems biology approach to explore metabolite repression of colibactin production in pks+ E. coli. We identify L-tryptophan as a repressor of colibactin genotoxicity that stimulates the expression of genes to export copper to the periplasm where it can inhibit ClbP, the colibactin-activating peptidase. These results work toward an antibiotic-sparing, prophylactic strategy to inhibit colibactin genotoxicity and its tumorigenic effects in the intestine.

Development and validation of a novel prognostic prediction system based on GLIM-defined malnutrition for colorectal cancer patients post-radical surgery

BackgroundMalnutrition often occurs in patients with colorectal cancer. This study aims to develop a predictive model based on GLIM criteria for patients with colorectal cancer who underwent radical surgery.MethodsFrom December 2015 to May 2021, patients with colorectal cancer who underwent radical surgery at our center were recruited for this study. We prospectively collected data on GLIM-defined malnutrition and other clinicopathological characteristics. Using Cox regeneration, we developed a novel nomogram for prognostic prediction, which was validated and compared to traditional nutritional factors for predictive accuracy.ResultsAmong the 983 patients enrolled in this study, malnutrition was identified in 233 (23.70%) patients. Multivariate analysis indicated that GLIM-defined malnutrition is the independent risk factor for overall survival (HR = 1.793, 95% CI = 1.390–2.313 for moderate malnutrition and HR = 3.485, 95% CI = 2.087–5.818 for severe malnutrition). The novel nomogram based on the GLIM criteria demonstrated a better performance than existing criteria, with AUC of 0.729, 0.703, and 0.683 for 1-year, 3-year, and 5-year OS, respectively, in the validation cohort. In addition, the risk score determined by this system exhibited significantly poorer short-term and long-term clinical outcomes in high-risk groups in both malnourished and well-nourished patients.ConclusionCombining handgrip strength, serum albumin level, and TNM stage would help improve the predictive effect of GLIM criteria for colorectal cancer patients post-radical surgery and benefit the individual prognostic prediction of colorectal cancer.

Lack of Association Between BsmI and FokI Polymorphisms of the VDR Gene and Sporadic Colorectal Cancer in a Romanian Cohort-A Preliminary Study.

Colorectal cancer (CRC) is a major public health problem worldwide, currently ranking third in cancer incidence and second in mortality. Multiple genes and environmental factors have been involved in the complex and multifactorial process of CRC carcinogenesis. VDR is an intracellular hormone receptor expressed in both normal epithelial and cancer colon cells at various levels. Several VDR gene polymorphisms, including FokI and BsmI, have been evaluated for their possible association with CRC susceptibility. The aim of our study was to investigate these two SNPs for the first time in Romanian CRC patients. FokI (rs228570 C>T) and BsmI (rs1544410 A>G) were genotyped by real-time polymerase chain reaction (RT-PCR) in 384-well plates using specific TaqMan predesigned probes on a ViiA™ 7 RT-PCR System. A total of 441 subjects (166 CRC patients and 275 healthy controls) were included. No statistically significant difference was observed between CRC patients and controls when we compared the wild-type genotype with heterozygous and mutant genotypes for both FokI (OR 0.85, 95% CI: 0.56-1.28; OR 0.95, 95% CI: 0.51-1.79, respectively) and BsmI (OR 0.97, 95% CI: 0.63-1.49; OR 1.10, 95% CI: 0.65-1.87, respectively) or in the dominant and recessive models. Also, we compared allele frequencies, and no correlation was found. Moreover, the association between these SNPs and the tumor site, TNM stage, and histological type was examined separately, and there was no statistically significant difference. In conclusion, our study did not show any association between FokI and BsmI SNPs and CRC susceptibility in a Romanian population. Further studies including a larger number of samples are needed to improve our knowledge regarding the influence of VDR polymorphism on CRC susceptibility.

Aberrant expression of miR-143/miR-223/miR4478 and miR145 as prognostic factor for colorectal cancer patients

Colorectal cancer (CRC) is a type of malignancy that develops in the colon or rectal region. It develops due to abnormal growth and proliferation of cells in the lining of the colon, forming a tumor. This study included tissue samples (56 malignant and 56 matched normal samples). miRNAs were determined and retrieved from miRBase database and moderated by p53 gene. Expression levels of miRNA were varied. Only miR-223 revealed greater expression than normal matched tissue. mMiR-143, miR-4478, and miR-145 exhibited lower expression than matched normal tissue. Only miR-143 and miR-145 showed considerable variations in the expression among groups while miR-4478 did not demonstrate statistically substantial difference. In conclusion, this study highlights that upregulation of P53 and miR-223 and downregulation of miR-145 and miR-143 were associated with cancer advancement and unfavorable prognosis in Saudi CRC patients, indicating P53, miR-223, miR-145 and miR-143 to be novel and valuable signatures for predicting the outcomes for patients with CRC.

Quality of life and somatic physical function of patients with colorectal cancer who underwent oxaliplatin-based systemic chemotherapy: a prospective study.

This study aimed to study the potential effects of oxaliplatin-based chemotherapy on cardiorespiratory fitness, handgrip strength (HGS), body composition, and quality of life (QoL) of stages III-IV colorectal cancer (CRC) patients before the first cycle (T0) and after the last cycle of systemic adjuvant/neoadjuvant chemotherapy (T1). Cardiorespiratory fitness, HGS, body composition, and QoL were evaluated with the six-minute walk test (6MWT), hydraulic hand dynamometer, body composition analyzer, and Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire in both T0 and T1, respectively. Twenty-eight CRC patients were included in this study. The total walked distance (TWD) was found to be decreased from T0 to T1 (499.72m vs. 488.56m); however, this change was not significant (z = -.706, p = 0.48). Type of chemotherapy whether adjuvant or neoadjuvant also showed no significant effect on TWD (z = -.1.372, p = .17 vs z = -1.180, p = .238, respectively). The QoL was significantly decreased (T0 = 118.35 vs T1 = 110.77, t = 2.176,p = 0.05). The TWD was significantly correlated with the physical well-being (PWB) subscale of FACT-C (r = .64, p = 0.001) as well as with HGS (r = .46, p = .018) in T0. After controlling for age, type of chemotherapy, and type of regimen, the HGS did not show a significant difference from T0 to T1 (F(1,23) = 1.557, p = .22, ηp2 = .06). However, the effect of time x gender showed significant difference from T0 to T1 (F(1,23) = 4.906, p = .037, ηp2 = .17). This study showed the decreased QoL and physical well-being of CRC patients who underwent oxaliplatin-based treatment. In addition, the gender effect of decreased HGS should be considered further when planning an oncological rehabilitation program.

Association between tumour-infiltrating lymphocyte-T CD8+ and programmed death-ligand 1 protein with the occurrence of metastasis in colorectal cancer patients: An observational study

Background: Tumour-infiltrating lymphocytes CD8+ (TILs CD8+) as an anticancer immune response and Programmed Death-Ligand 1 (PD-L1) as an immune checkpoint molecule expression are important in colorectal cancer (CRC) as their expression correlates with the immune status and the progression of cancer. The primary objective of this study is to examine the relationship between TILs CD8+ and PD-L1 expression levels and CRC metastasis to provide insights into the immune microenvironment’s role in CRC progression and metastasis, potentially improving patient outcomes and treatment response. Methods: This study was an observational study involving colorectal cancer patients who were treated at a tertiary hospital in Bandung, West Java, Indonesia. There were 40 patients included in the study. Tumour tissue samples were collected from patients, and immunohistochemical staining was performed to evaluate TILs CD8+ infiltration and PD-L1 expression levels. Clinical data, including metastasis occurrences, were collected from the cancer registry. Results: Analysis of TILs CD8+ and PD-L1 expression levels in CRC patients revealed significant findings regarding metastasis occurrence and cancer staging. There was a notable positive correlation between PD-L1 expression and TILs-CD8+ infiltration in the presence of distant metastasis and advanced cancer stage (p &lt; 0.05). However, no significant association was observed between TILs CD8 and PD-L1 expression levels and lymphatic metastasis. Conclusion: This study highlights the potential prognostic value of TILs CD8+ and PD-L1 expression levels in predicting CRC progression and metastasis. However, the lack of a significant correlation with lymphatic metastasis suggests the need for further investigation into the underlying mechanisms. Understanding the roles of PD-L1 and TILs-CD8+ expression in CRC metastasis may facilitate the development of targeted therapeutic strategies to improve patient outcomes.

COL25A1 and METAP1D DNA methylation are promising liquid biopsy epigenetic biomarkers of colorectal cancer using digital PCR

BackgroundColorectal cancer is a public health issue and was the third leading cause of cancer-related death worldwide in 2022. Early diagnosis can improve prognosis, making screening a central part of colorectal cancer management. Blood-based screening, diagnosis and follow-up of colorectal cancer patients are possible with the study of cell-free circulating tumor DNA. This study aimed to identify novel DNA methylation biomarkers of colorectal cancer that can be used for the follow-up of patients with colorectal cancer.MethodsA DNA methylation profile was established in the Gene Expression Omnibus (GEO) database (n = 507) using bioinformatics analysis and subsequently confirmed using The Cancer Genome Atlas (TCGA) database (n = 348). The in silico profile was then validated on local tissue and cell-free DNA samples using methylation-specific digital PCR in colorectal cancer patients (n = 35) and healthy donors (n = 35).ResultsThe DNA methylation of COL25A1 and METAP1D was predicted to be a colorectal cancer biomarker by bioinformatics analysis (ROC AUC = 1, 95% CI [0.999–1]). The two biomarkers were confirmed with tissue samples, and the combination of COL25A1 and METAP1D yielded 49% sensitivity and 100% specificity for cell-free DNA.ConclusionBioinformatics analysis of public databases revealed COL25A1 and METAP1D DNA methylation as clinically applicable liquid biopsies DNA methylation biomarkers. The specificity implies an excellent positive predictive value for follow-up, and the high sensitivity and relative noninvasiveness of a blood-based test make these biomarkers compatible with colorectal cancer screening. However, the clinical impact of these biomarkers in colorectal cancer screening and follow-up needs to be established in further prospective studies.

Oral Microbial Translocation Genes in Gastrointestinal Cancers: Insights from Metagenomic Analysis

Along with affecting oral health, oral microbial communities may also be endogenously translocated to the gut, thereby mediating the development of a range of malignancies in that habitat. While species-level studies have proven the capability of oral pathogens to migrate to the intestine, genetic evidence supporting this mechanism remains insufficient. In this study, we identified over 55,000 oral translocation genes (OTGs) associated with colorectal cancer (CRC) and inflammatory bowel disease (IBD). These genes are primarily involved in signal transduction and cell wall biosynthesis and show consistency in their functions between IBD and CRC. Furthermore, we found that Leclercia adecarboxylata, a newly discovered opportunistic pathogen, has a significantly high abundance in the gut microbiota of colorectal cancer patients. OTGs of this pathogen were enriched in 15 metabolic pathways, including those associated with amino acid and cofactor metabolism. These findings, for the first time, provide evidence at the genetic level of the transfer of oral pathogens to the intestine and offer new insights into the understanding of the roles of oral pathogens in the development of gastrointestinal cancers.