Outcome In Colorectal Cancer Patients Research Articles

Prognostic nomograms integrating preoperative serum lipid derivative and systemic inflammatory marker of patients with non-metastatic colorectal cancer undergoing curative resection.

Lipid metabolism and cancer-related inflammation are closely related to the progression and prognosis of colorectal cancer (CRC). Therefore, this study aims to establish novel nomograms based on the combined detection of preoperative blood lipids and systemic inflammatory indicators to predict the overall survival (OS) and cancer-specific survival (CCS) of CRC patients. A total of 523 patients with stage I-III CRC in our institute were collected from 2014 to 2018. The independent predictors for OS and CCS were determined by forward stepwise Cox regression for the establishment of prognostic models. The superiorities of different models were compared by concordance index (C-index), Akaike information criterion (AIC) and integrated discrimination improvement analysis. The performance of the nomograms based on the optimal models was measured by the plotting time-dependent receiver operating characteristic curves, calibration curves, and decision curves, and compared with the tumor-node-metastasis (TNM) staging system. The cohort was categorized into low-risk, medium-risk and high-risk groups according to the risk points of the nomogram, and analyzed using Kaplan-Meier curves and log-rank test. Preoperative TG/HDL-C ratio (THR) ≥ 1.93 and prognostic nutritional index (PNI) ≥ 42.55 were independently associated with favorable outcomes in CRC patients. Six (pT stage, pN stage, histological subtype, perineural invasion, THR and PNI) and seven (pT stage, pN stage, histological subtype, perineural invasion, gross appearance, THR and PNI) variables were chosen to develop the optimal models and construct nomograms for the prediction of OS and CCS. The models had lower AIC and larger C-indexes than other models lacking either or both of THR and PNI, and improved those integrated discrimination ability significantly. The nomograms showed better discrimination ability, calibration ability and clinical effectiveness than TNM system in predicting OS and CCS, and these results were reproducible in the validation cohort. The three risk stratifications based on the nomograms presented significant discrepancies in prognosis. Preoperative THR and PNI have distinct prognostic value in stage I-III CRC patients. The nomograms incorporated the two indexes provide an intuitive and reliable approach for predicting the prognosis and optimizing individualized therapy of non-metastatic CRC patients, which may be a complement to the TNM staging system.

Reprogramming of palmitic acid induced by dephosphorylation of ACOX1 promotes β-catenin palmitoylation to drive colorectal cancer progression

Metabolic reprogramming is a hallmark of cancer. However, it is not well known how metabolism affects cancer progression. We identified that metabolic enzyme acyl-CoA oxidase 1 (ACOX1) suppresses colorectal cancer (CRC) progression by regulating palmitic acid (PA) reprogramming. ACOX1 is highly downregulated in CRC, which predicts poor clinical outcome in CRC patients. Functionally, ACOX1 depletion promotes CRC cell proliferation in vitro and colorectal tumorigenesis in mouse models, whereas ACOX1 overexpression inhibits patient-derived xenograft growth. Mechanistically, DUSP14 dephosphorylates ACOX1 at serine 26, promoting its polyubiquitination and proteasomal degradation, thereby leading to an increase of the ACOX1 substrate PA. Accumulated PA promotes β-catenin cysteine 466 palmitoylation, which inhibits CK1- and GSK3-directed phosphorylation of β-catenin and subsequent β-Trcp-mediated proteasomal degradation. In return, stabilized β-catenin directly represses ACOX1 transcription and indirectly activates DUSP14 transcription by upregulating c-Myc, a typical target of β-catenin. Finally, we confirmed that the DUSP14-ACOX1-PA-β-catenin axis is dysregulated in clinical CRC samples. Together, these results identify ACOX1 as a tumor suppressor, the downregulation of which increases PA-mediated β-catenin palmitoylation and stabilization and hyperactivates β-catenin signaling thus promoting CRC progression. Particularly, targeting β-catenin palmitoylation by 2-bromopalmitate (2-BP) can efficiently inhibit β-catenin-dependent tumor growth in vivo, and pharmacological inhibition of DUSP14-ACOX1-β-catenin axis by Nu-7441 reduced the viability of CRC cells. Our results reveal an unexpected role of PA reprogramming induced by dephosphorylation of ACOX1 in activating β-catenin signaling and promoting cancer progression, and propose the inhibition of the dephosphorylation of ACOX1 by DUSP14 or β-catenin palmitoylation as a viable option for CRC treatment.

The association of preoperative high-sensitivity cardiac troponin i and long-term outcomes in colorectal cancer patients received tumor resection surgery

BackgroundThis study aimed to evaluate the association between preoperative hs-cTnI and long-term mortality and major adverse cardiovascular events (MACE) in colorectal cancer patients.MethodsThis single-center retrospective cohort study included 1105 consecutive colorectal cancer patients who received tumor resection surgery between January 2018 and June 2020. Inclusion criteria were an age ≥ 18 years and had been tested for hs-cTnI on admission within 7 days prior to tumor resection surgery. Exclusion criteria were emergent surgery, failure to received tumor resection surgery, hospital death, there was clinical evidence of unstable coronary artery disease or pulmonary embolism occurred before operation according to medical record. The primary endpoint was all-cause death. Secondary endpoint was major adverse cardiovascular events (MACE).ResultsA total of 1105 patients were enrolled: 1032 with normal hs-cTnI and 73 with elevated hs-cTnI. The mean follow-up was 24.4 ± 10.8 months, 176 patients died and 39 patients met MACE. In the elevated troponin group, 50%, 32.1% and 17.9% died from cancer, cardiovascular and other causes, while those in the normal troponin group were 75.7%, 2% and 22.3%, there was statistical difference between 2 groups (P < 0.001). Patients with elevated preoperative hs-cTnI had significantly higher mortality (P < 0.001) and more MACE (P < 0.001) compared with those with normal hs-cTnI. A propensity-matching analysis were performed, resulting in 151 patients with normal hs-cTnI and 60 patients with elevated hs-cTnI. The matched population had the similar results for all-cause death (P = 0.009) and MACE (P = 0.001). The results were consistent after further excluding 147 patients who had received chemoradiotherapy prior to surgery in subgroup analysis. The results of multivariate Cox regression analysis shown that hs-cTnI was one of the best predictors for all-cause death (hazard ratio [HR] 2.278; 95% confidence interval [CI] 1.19–4.361) and MACE (HR, 3.523; 95%CI, 1.477–8.403) in total populations, similar results were found in subgroup analysis.ConclusionsColorectal cancer patients without myocardial ischemia manifestation but with elevated hs-cTnI prior to tumor resection surgery were at increased risk for long-term all-cause death and MACE, irrespective of whether they have received chemoradiotherapy prior to surgery.

Phenotypic subtypes predict outcomes in colorectal cancer

BackgroundColorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. The Colorectal Cancer Subtyping Consortium used the transcriptome-based method to classify CRC according to four molecular subtypes, each showing different genomic alterations and prognoses: CMS1 (microsatellite instable [MSI] immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal). To expedite the clinical implementation of such methods, easier and preferably tumor phenotype–based methods are needed. In this study, we describe a method to divide patients into four phenotypic subgroups using immunohistochemistry. Moreover, we analyze disease-specific survival (DSS) among different phenotypic subtypes and the associations between the phenotypic subtypes and clinicopathological variables.MethodsWe categorized 480 surgically treated CRC patients into four phenotypic subtypes (immune, canonical, metabolic, and mesenchymal) using the immunohistochemically determined CD3–CD8 tumor–stroma index, proliferation index, and tumor–stroma percentage. We analyzed survival rates for the phenotypic subtypes in different clinical patient subgroups using the Kaplan–Meier method and Cox regression analysis. Associations between phenotypic subtypes and clinicopathological variables were examined using the chi-square test.ResultsPatients with immune subtype tumors exhibited the best 5-year DSS, while mesenchymal subtype tumors accompanied the worst prognosis. The prognostic value of the canonical subtype showed wide variation among different clinical subgroups. Immune subtype tumors were associated with being female, stage I disease, and a right-side colon location. Metabolic tumors, however, were associated with pT3 and pT4 tumors, and being male. Finally, a mesenchymal subtype associated with stage IV disease, a mucinous histology, and a rectal tumor location.ConclusionsPhenotypic subtype predicts patient outcome in CRC. Associations and prognostic values for subtypes resemble the transcriptome-based consensus molecular subtypes (CMS) classification. In our study, the immune subtype stood out with its exceptionally good prognosis. Moreover, the canonical subtype showed wide variability among clinical subgroups. Further studies are needed to investigate the concordance between transcriptome-based classification systems and the phenotypic subtypes.

Hypoalbuminemia and colorectal cancer patients: Any correlation?: A systematic review and meta-analysis.

In malnourished patients with colorectal cancer, hypoalbuminemia is common and was proposed to determine the postoperative outcome of colorectal surgery. Mounting articles published but have not been evaluated. We aim to assess the predictive value of preoperative hypoalbuminemia in patients undergoing colorectal surgery. We performed a literature search from PubMed, Euro PMC, and Cochrane with the terms serum albumin, hypoalbuminemia, prognosis, outcome, colorectal cancer, and neoplasm. We also hand-searched and included any relevant papers. Hypoalbuminemia is defined as plasma albumin level < 3.5 mg/dL. We restricted the included studies to English language and adults undergoing colectomy, laparotomy, laparoscopy, or abdominoperineal resection. Any types of articles were included, except an abstract-only publication and those that did not report the key exposure or outcome of interest. The key exposures were mortality, hospitalization time, and morbid conditions (thrombosis, surgical site infection, sepsis, and wound events). We pooled the odds ratio from each included literature as effect size. The Newcastle Ottawa scale and GRADE were used to determine the quality of each included study. Hereof 7 observational studies (236,480 individuals) were included. Our meta-analysis found that preoperative hypoalbuminemia can predict the postoperative outcome in colorectal cancer patients. Individuals with hypoalbuminemia were not associated with 30-day mortality (risk ratio [RR] 2.05 [0.72, 5.86], P = .18, I2 = 99%) but were associated with morbidity (RR 2.28 [1.78, 2.93], P < .00001, I2 = 87.5%), surgical complication (RR 1.69 [1.34, 2.13], P < .00001, I2 = 98%), and hospitalization (RR 2.21 [1.93, 2.52], P < .00001, I2 = 0%). According to newcastle ottawa scale, the included studies are of moderate to sound quality. The current systematic review and meta-analysis showed that preoperative hypoalbuminemia was significantly associated with morbidity, length of stay, and surgical complication but not mortality.

Construction of a TTN Mutation-Based Prognostic Model for Evaluating Immune Microenvironment, Cancer Stemness, and Outcomes of Colorectal Cancer Patients.

Colorectal cancer (CRC) is one of the commonest cancers worldwide. As conventional biomarkers cannot clearly define the heterogeneity of CRC, it is essential to establish novel prognostic models. For the training set, data pertaining to mutations, gene expression profiles, and clinical parameters were obtained from the Cancer Genome Atlas. Consensus clustering analysis was used to identify the CRC immune subtypes. CIBERSORT was used to analyze the immune heterogeneity across different CRC subgroups. Least absolute shrinkage and selection operator regression was used to identify the genes for constructing the immune feature-based prognostic model and to determine their coefficients. A gene prognostic model was then constructed to predict patient outcomes; the model was then externally validated using data from the Gene Expression Omnibus. As a high-frequency somatic mutation, the titin (TTN) mutation has been identified as a risk factor for CRC. Our results demonstrated that TTN mutations have the potential to modulate the tumor microenvironment, converting it into the immunosuppressive type. In this study, we identified the immune subtypes of CRC. Based on the identified subtypes, 25 genes were selected for prognostic model construction; a prediction model was also constructed, and its prediction accuracy was tested using the validation dataset. The potential of the model in predicting immunotherapy responsiveness was then explored. TTN-mutant and TTN-wild-type CRC demonstrated different microenvironment features and prognosis. Our model provides a robust immune-related gene prognostic tool and a series of gene signatures for evaluating the immune features, cancer stemness, and prognosis of CRC.

Association between small nucleolar RNA host gene expression and survival outcome of colorectal cancer patients: A meta-analysis based on PRISMA and bioinformatics analysis.

Growing evidence shows that long non-coding RNA small nucleolar RNA host genes (lncRNA SNHGs) enact an pivotal regulatory roles in the shorter survival outcome of colorectal cancer (CRC). However, no research has systematically evaluated the correlation among lncRNA SNHGs expression and survival outcome of CRC. This research indented to screen whether exist potential prognostic effect of lncRNA SNHGs in CRC patientss using comprehensive review and meta-analysis. Systematic searches were performed from the six relevant databases from inception to October 20, 2022. The quality of published papers was evaluated in details. We pooled the hazard ratios (HR) with 95% confidence interval (CI) through direct or indirect collection of effect sizes, and odds ratios (OR) with 95% CI by collecting effect sizes within articles. Detailed downstream signaling pathways of lncRNA SNHGs were summarized in detail. 25 eligible publications including 2,342 patients were finally included to appraise the association of lncRNA SNHGs with prognosis of CRC. Elevated lncRNA SNHGs expression was revealed in colorectal tumor tissues. High lncSNHG expression means bad survival prognosis in CRC patients (HR=1.635, 95% CI: 1.405-1.864, P<0.001). Additionally, high lncRNA SNHGs expression was inclined to later TNM stage (OR=1.635, 95% CI: 1.405-1.864, P<0.001), distant lymph node invasion, distant organ metastasis, larger tumor diameter and poor pathological grade. Begg's funnel plot test using the Stata 12.0 software suggested that no significant heterogeneity was found. Elevated lncRNA SNHGs expression was revealed to be positively correlated to discontented CRC clinical outcome and lncRNA SNHG may act as a potential clinical prognostic index for CRC patients.

Correlation of serum IGF-1, AGEs and their receptors with the risk of colorectal cancer in patients with type 2 diabetes mellitus.

According to epidemiological evidence, people with type 2 diabetes mellitus have a higher risk of developing colorectal cancer. To examine the relationship between colorectal cancer (CRC) and serum levels of IGF-1, IGF-1R, AGEs,RAGE and sRAGE in patients with type 2 diabetes. By using RNA-Seq data of CRC patients from The Cancer Genome Atlas (TCGA) database, we divided the patients into normal group(58 patients)and tumor group(446 patients), and analyzed the expression and prognostic value analysis of IGF-1,IGF1R and RAGE. Cox regression and the Kaplan-Meier method were used to determine the predictive value of target gene on clinical outcomes in CRC patients. In order to further combine CRC with diabetes research,one hundred forty-eight patients hospitalized in the Second Hospital of Harbin Medical University from July 2021 to July 2022 were enrolled and divided into CA and control groups. There were 106 patients in the CA group, including 75 patients with CRC and 31 patients with CRC+T2DM; the control group comprised 42 patients with T2DM. Circulating levels of IGF-1, IGF-1R, AGEs, RAGE, and sRAGE in the serum of the patients were measured using Enzyme-Linked Immunosorbnent Assay(ELISA) kits, and other clinical parameters were also measured during hospitalization. Statistical methods used were χ² test, independent samples t-test and Pearson correlation analysis were. Finally, we controlled for confounding factors and used logistic multi-factor regression analysis. Bioinformatics analysis showed that IGF-1, IGF1R and RAGE were highly expressed in CRC patients, and the patients with high expression also showed significantly lower overall survival rate. Through Cox regression analysis, IGF-1 can be used as an independent influencing factor of CRC. In the ELISA experiment, serum AGE, RAGE, IGF-1, and IGF-1R levels were higher in the CRC and CRC+T2DM groups than in the T2DM group, but the serum sRAGE concentrations in these groups were lower than those in the T2DM group (P < 0.05). Serum AGE, RAGE, sRAGE, IGF1, and IGF1R levels were higher in the CRC+T2DM group than in the CRC group (P < 0.05). In CRC+T2DM patients, serum AGEs were correlated with age (p = 0.027), and the serum AGE levels in these groups were positively correlated with RAGE and IGF-1 levels (p < 0.001) and negatively correlated with sRAGE and IGF-1R levels (p < 0.001). After correcting for confounding factors based on logistic multiple regression analysis, the effects of age, serum IGF-1 and IGF-1R on the development of CRC in patients with T2DM were statistically significant (p<0.05). Serum IGF-1 and IGF-1R levels independently influenced the development of CRC in patients with T2DM. Furthermore, IGF-1 and IGF-1R were correlated with AGEs in CRC patients who also had T2DM, suggesting that AGEs may influence the development of CRC in T2DM patients. These findings suggest that we may be able to lower the risk of CRC in the clinic by regulating AGEs through the regulation of blood glucose levels, which will affect IGF-1 and its receptors.

Oncologic outcomes of first-line bevacizumab/FOLFIRI in combination with Ginsenoside-modified nanostructured lipid carrier containing curcumin in unresectable metastatic colorectal cancer patients

Background: The patients with unresectable metastatic colorectal cancer has dismal survival outcomes even though they received standard palliative chemotherapy. Furthermore, current chemotherapy is often associated with various adverse events. A number of studies suggested that curcumin has shown anticancer effects with low toxicity, but there was a lack of long-term survival outcomes of treatment in combination with curcumin and standard chemotherapy in metastatic colorectal cancer patients. This study aimed to evaluate the long-term oncologic outcomes in colorectal cancer patients with unresectable metastases after treatment with first-line bevacizumab/FOLFIRI in combination with a dietary supplement of ginsenoside modified nanostructure lipid carrier containing curcumin (G-NLC).

Prognostic significance of sarcopenia diagnosed based on the anthropometric equation for progression-free survival and overall survival in patients with colorectal cancer.

The purpose of this study was to investigate the prognostic significance of sarcopenia diagnosed based on anthropometric equations for progression-free survival (PFS) and overall survival (OS) in patients with colorectal cancer (CRC). A total of 1,441 CRC patients who underwent surgical treatment between January 2012 and December 2016 were enrolled in this study. Sarcopenia was diagnosed according to validated anthropometric equations. The Kaplan-Meier method with the log-rank test was used to estimate the survival curve. Cox proportional hazards regression models with forward selection were used to evaluate risk factors affecting the prognosis of CRC patients. R package "survival" was used to build the prognostic nomograms to predict 1-5 years of PFS and OS in CRC patients. The concordance index (C-index) and calibration curve were used to evaluate the prognostic accuracy of the prognostic nomogram. Two hundred and seventy-one patients (18.8%) were diagnosed with sarcopenia. Sarcopenia was significantly associated with advanced age, large tumor size, and high mortality. Compared with the non-sarcopenia patients, the PFS of sarcopenia patients was worse (5-year PFS, 48.34 vs. 58.80%, p = 0.003). Multivariate survival analysis showed that patients with sarcopenia had a higher risk (23.9%) of adverse PFS (HR, 1.239; 95%CI: 1.019-1.505, p = 0.031) than patients without sarcopenia. The OS of patients with sarcopenia was significantly worse than that of patients without sarcopenia (5-year OS: 50.92 vs. 61.62%, p = 0.001). In CRC patients, sarcopenia was independently associated with poor OS (HR: 1.273, 95%CI: 1.042-1.556, p < 0.001). Moreover, sarcopenia effectively differentiated the OS of CRC patients in the normal carcinoembryonic antigen (CEA) subgroup but not in the high CEA subgroup. Notably, sarcopenia can provide effective prognostic stratification in CRC patients at different pathological stages. Nomograms that integrated prognostic features were built to predict the risk of adverse outcomes in CRC patients. The C-index and calibration curves showed that these nomograms had good prediction accuracy. Internal validation confirmed that our nomogram has wide application potential. Sarcopenia diagnosed based on anthropometric equations is an independent risk factor for PFS and OS in CRC patients.

Dysbiotic microbiome variation in colorectal cancer patients is linked to lifestyles and metabolic diseases

BackgroundDifferences in the composition and diversity of the gut microbial communities among individuals are influenced by environmental factors. However, there is limited research on factors affecting microbiome variation in colorectal cancer patients, who display lower inter-individual variations than that of healthy individuals. In this study, we examined the association between modifiable factors and the microbiome variation in colorectal cancer patients.MethodsA total of 331 colorectal cancer patients who underwent resection surgery at the Department of Surgery, Seoul National University Hospital between October 2017 and August 2019 were included. Fecal samples from colorectal cancer patients were collected prior to the surgery. Variations in the gut microbiome among patients with different lifestyles and metabolic diseases were examined through the network analysis of inter-connected microbial abundance, the assessment of the Anna Karenina principle effect for microbial stochasticity, and the identification of the enriched bacteria using linear discrimination analysis effect size. Associations of dietary diversity with microbiome variation were investigated using the Procrustes analysis.ResultsWe found stronger network connectivity of microbial communities in non-smokers, non-drinkers, obese individuals, hypertensive subjects, and individuals without diabetes than in their counterparts. The Anna Karenina principle effect was found for history of smoking, alcohol consumption, and diabetes (with significantly greater intra-sample similarity index), whereas obesity and hypertension showed the anti-Anna Karenina principle effect (with significantly lower intra-sample similarity index). We found certain bacterial taxa to be significantly enriched in patients of different categories of lifestyles and metabolic diseases using linear discrimination analysis. Diversity of food and nutrient intake did not shape the microbial diversity between individuals (pProcrustes>0.05).ConclusionsOur findings suggested an immune dysregulation and a reduced ability of the host and its microbiome in regulating the community composition. History of smoking, alcohol consumption, and diabetes were shown to affect partial individuals in shifting new microbial communities, whereas obesity and history of hypertension appeared to affect majority of individuals and shifted to drastic reductions in microbial compositions. Understanding the contribution of modifiable factors to microbial stochasticity may provide insights into how the microbiome regulates effects of these factors on the health outcomes of colorectal cancer patients.

A new natural killer cell-specific gene signature predicting recurrence in colorectal cancer patients.

The protective role of Natural Killer (NK) cell tumour immunosurveillance has long been recognised in colorectal cancer (CRC). However, as most patients show limited intra-tumoral NK cell infiltration, improving our ability to identify those with high NK cell activity might aid in dissecting the molecular features which underlie NK cell sensitivity. Here, a novel CRC-specific NK cell gene signature that infers NK cell load in primary tissue samples was derived and validated in multiple patient CRC cohorts. In contrast with other NK cell gene signatures that have several overlapping genes across different immune cell types, our NK cell signature has been extensively refined to be specific for CRC-infiltrating NK cells. The specificity of the signature is substantiated in tumour-infiltrating NK cells from primary CRC tumours at the single cell level, and the signature includes genes representative of NK cells of different maturation states, activation status and anatomical origin. Our signature also accurately discriminates murine NK cells, demonstrating the applicability of this geneset when mining datasets generated from preclinical studies. Differential gene expression analysis revealed tumour-intrinsic features associated with NK cell inclusion versus exclusion in CRC patients, with those tumours with predicted high NK activity showing strong evidence of enhanced chemotactic and cytotoxic transcriptional programs. Furthermore, survival modelling indicated that NK signature expression is associated with improved survival outcomes in CRC patients. Thus, scoring CRC samples with this refined NK cell signature might aid in identifying patients with high NK cell activity who could be prime candidates for NK cell directed immunotherapies.

DDX17 induces epithelial-mesenchymal transition and metastasis through the miR-149-3p/CYBRD1 pathway in colorectal cancer

DEAD box helicase 17 (DDX17) has been reported to be involved in the initiation and development of several cancers. However, the functional role and mechanisms of DDX17 in colorectal cancer (CRC) malignant progression and metastasis remain unclear. Here, we reported that DDX17 expression was increased in CRC tissues compared with noncancerous mucosa tissues and further upregulated in CRC liver metastasis compared with patient-paired primary tumors. High levels of DDX17 were significantly correlated with aggressive phenotypes and worse clinical outcomes in CRC patients. Ectopic expression of DDX17 promoted cell migration and invasion in vitro and in vivo, while the opposite results were obtained in DDX17-deficient CRC cells. We identified miR-149-3p as a potential downstream miRNA of DDX17 through RNA sequencing analysis, and miR-149-3p displayed a suppressive effect on the metastatic potential of CRC cells. We demonstrated that CYBRD1 (a ferric reductase that contributes to dietary iron absorption) was a direct target of miR-149-3p and that miR-149-3p was required for DDX17-mediated regulation of CYBRD1 expression. Moreover, DDX17 contributed to the metastasis and epithelial to mesenchymal transition (EMT) of CRC cells via downregulation of miR-149-3p, which resulted in increased CYBRD1 expression. In conclusion, our findings not only highlight the significance of DDX17 in the aggressive development and prognosis of CRC patients, but also reveal a novel mechanism underlying DDX17-mediated CRC cell metastasis and EMT progression through manipulation of the miR-149-3p/CYBRD1 pathway.

Integration of liquid biopsy and immunotherapy: opening a new era in colorectal cancer treatment.

Immunotherapy has revolutionized the conventional treatment approaches for colorectal cancer (CRC), offering new therapeutic prospects for patients. Liquid biopsy has shown significant potential in early screening, diagnosis, and postoperative monitoring by analyzing circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). In the era of immunotherapy, liquid biopsy provides additional possibilities for guiding immune-based treatments. Emerging technologies such as mass spectrometry-based detection of neoantigens and flow cytometry-based T cell sorting offer new tools for liquid biopsy, aiming to optimize immune therapy strategies. The integration of liquid biopsy with immunotherapy holds promise for improving treatment outcomes in colorectal cancer patients, enabling breakthroughs in early diagnosis and treatment, and providing patients with more personalized, precise, and effective treatment strategies.

MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients

MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients

Preoperative Immunocite-Derived Ratios Predict Surgical Complications Better when Artificial Neural Networks Are Used for Analysis-A Pilot Comparative Study.

We aimed to comparatively assess the prognostic preoperative value of the main peripheral blood components and their ratios-the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR)-to the use of artificial-neural-network analysis in determining undesired postoperative outcomes in colorectal cancer patients. Our retrospective study included 281 patients undergoing elective radical surgery for colorectal cancer in the last seven years. The preoperative values of SII, NLR, LMR, and PLR were analyzed in relation to postoperative complications, with a special emphasis on their ability to accurately predict the occurrence of anastomotic leak. A feed-forward fully connected multilayer perceptron network (MLP) was trained and tested alongside conventional statistical tools to assess the predictive value of the abovementioned blood markers in terms of sensitivity and specificity. Statistically significant differences and moderate correlation levels were observed for SII and NLR in predicting the anastomotic leak rate and degree of postoperative complications. No correlations were found between the LMR and PLR or the abovementioned outcomes. The MLP network analysis showed superior prediction value in terms of both sensitivity (0.78 ± 0.07; 0.74 ± 0.04; 0.71 ± 0.13) and specificity (0.81 ± 0.11; 0.69 ± 0.03; 0.9 ± 0.04) for all the given tasks. Preoperative SII and NLR appear to be modest prognostic factors for anastomotic leakage and overall morbidity. Using an artificial neural network offers superior prognostic results in the preoperative risk assessment for overall morbidity and anastomotic leak rate.

FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC.

Background: Metastasis accounts for the high lethality of colorectal cancer (CRC) patients. Unfortunately, the molecular mechanism manipulating metastasis in CRC is still elusive. Here, we investigated the function of E74-like factor 4 (ELF4), an ETS family member, in facilitating CRC progression. Methods: The expression of ELF4 in human CRC samples and CRC cell lines was determined by quantitative real-time PCR, immunohistochemistry and immunoblotting. The migratory and invasive phenotypes of CRC cells were evaluated by in vitro transwell assays and in vivo metastatic models. The RNA sequencing was used to explore the downstream targets of ELF4. The luciferase reporter assays and chromatin immunoprecipitation assays were used to ascertain the transcriptional regulation related to ELF4. Results: We found elevated ELF4 was positively correlated with distant metastasis, advanced AJCC stages, and dismal outcomes in CRC patients. ELF4 expression was also an independent predictor of poor prognosis. Overexpression of ELF4 boosted CRC metastasis via transactivating its downstream target genes, fibroblast growth factor receptor 4 (FGFR4) and SRC proto-oncogene, non-receptor tyrosine kinase, SRC. Fibroblast growth factor 19 (FGF19) upregulated ELF4 expression through the ERK1/2/SP1 axis. Clinically, ELF4 expression had a positive correlation with FGF19, FGFR4 and SRC, and CRC patients who positively coexpressed FGF19/ELF4, ELF4/FGFR4, or ELF4/SRC exhibited the worst clinical outcomes. Furthermore, the combination of the FGFR4 inhibitor BLU-554 and the SRC inhibitor KX2-391 dramatically suppressed ELF4-mediated CRC metastasis. Conclusions: We demonstrated the essentiality of ELF4 in the metastatic process of CRC, and targeting the ELF4-relevant positive feedback circuit might represent a novel therapeutic strategy.

Are health outcomes in the older colorectal cancer patients treated by curative intent surgery any different to the younger patients?

Colorectal cancer poses a major burden. Its incidence increases with age and older patients with comorbidities have a higher likelihood of major complications. This study investigated the impact of age on health outcomes in colorectal cancer patients treated by surgery. A prospective database of all patients undergoing colorectal cancer surgery with curative intent between 2012 and 2017 was used to identify patients. A retrospective review of existing medical records investigating health-related outcomes in colorectal cancer patients undergoing surgery was performed. Primary outcomes measured were overall survival (OS) and disease-free survival (DFS). Difference in restricted mean survival times (RMST) up to a pre-specified time point of 24 months was used to compare four age groups. Six-hundred and fifty-one patients were divided into four age group categories: ≤65-years (n= 244), 66 to 75-years (n= 213), 76 to 85-years (n= 162) and >85-years (n= 32). Older patients were found to have a higher rate of post-operative medical complications (including confusion) (P= 0.001) and a longer length of stay (LOS) (P= 0.01). There was no difference between the 76 to 85-year age group and >85-year age group in OS and DFS. However, there was a reduced OS in older patients (>65) compared to their younger cohorts (<65) (P= 0.04). Older patients who undergo curative surgery have reduced OS, increased LOS and higher complication rates. Complex older patients may benefit from geriatric assessment and management in the peri-operative period.

Effect of Surgical Starting Time and Season on Prognosis in Octogenarians with Colorectal Cancer: A Retrospective Study

Aim: To investigate the effect of surgical starting time and season on the prognosis of octogenarians with colorectal cancer. Patients & methods: A total of 291 patients aged 80years or above who received elective colectomy for colorectal cancer between January 2007 and December 2018 in the National Cancer Center in China were included. Results: No significant time- or season-dependent difference in overall survival for all clinical stages was found in the study. Comparing perioperative outcomes, the morning group had a longer operative time than the afternoon group (p=0.03), but no significant difference was found based on the season of colectomy. Conclusion: These findings provide insights into clinical outcomes for colorectal cancer patients aged more than 80years.

The Effect of the Mucinous Component Presence on the Clinical Outcomes of Colorectal Cancer

Background. The effect of colorectal cancer (CRC) histological subtypes on the prognosis is still a controversial issue. We aimed to compare clinical findings, histopathologic data, and survival outcomes in CRC patients with classical and mucinous subtypes.&#x0D; Methods. Patients who were operated on for CRC between 2010 and 2017 were included in the study. Patients were classified into two groups according to the presence of a mucinous component: mucinous adenocarcinoma (MAC) - mucinous component &gt; 50% and classical adenocarcinoma (CAC). Clinical and histopathologic findings, recurrence, metastasis, and survival rates were compared.&#x0D; Results. Data of the 484 CRC patients were documented. Sixty-nine patients (14.3%) were in the MAC group and 415 (85.7%) patients were in the CAC group. The mean age of patients with MAC and CAC was 63.4 ± 13.5 and 68.5 ± 12.7 years, respectively (p = 0.002). Proximal colon localization was found in 30 (43.5%) MAC patients and 123 (29.6%) CAC patients (p = 0.029). The number of patients with metastatic lymph nodes was higher in the MAC group (58% vs. 41.2%, p = 0.03). Nevertheless, there was no significant difference between the CAC and MAC groups in terms of disease-free survival (63.1% vs. 69.6%, p = 0.37) and disease-related mortality (23.6% vs. 23.2%, p = 0.94) over the follow-up period. Multivariate analysis showed that the presence of perineural invasion, patient’s age, and disease stage were associated with mortality in CRC patients.&#x0D; Conclusions. MACs occurred at a younger age than CACs and were more likely localized in the proximal colon as compared to CACs. Despite increased lymph node metastasis in MAC patients, no statistical significance was detected in overall survival or disease-free survival. Multivariate analysis revealed that age, perineural invasion, and disease stage were relevant to mortality in CRC patients.