Colorectal Cancer Prediction Research Articles

Predictive Ability of Neutrophil-Lymphocyte Ratio in Determining Tumor Staging in Colorectal Cancer.

IntroductionTumor staging plays an important role in determining treatment in colorectal cancer. In the recent past, the neutrophil-lymphocyte ratio (NLR) has been used as a predictive marker of inflammation for different types of clinical entities. Our study aims to determine if NLR can predict tumor staging in patients with colorectal cancer.Materials and methodsWe retrospectively analyzed all cases that underwent surgical treatment for colorectal cancer from 2014 to 2020. The NLR, tumor stage, and histology report for all patients were reviewed. Recommended cut-off values for NLR for tumor stage (T), lymph node stage (N), and metastatic stage (M) were determined using receiver operating characteristic (ROC) analysis. ResultsNLR was found to be significantly higher in patients with T3-T4 tumors as compared to T1-T2 tumors (mean: 5.8 vs. 2.6, respectively p < 0.001). The NLR values were higher in cases of N1-N2 groups as compared to N0 groups (mean: 5.7 vs. 3.5, p = 0.07). The NLR was also higher in M1 patients as compared to M0 patients (32.1 vs. 4.5, respectively, p = 0.24) but failed to show a statistical significance.ConclusionNLR is a useful predictor of colorectal cancer which can give us some information about the type of tumor we may encounter during surgery.

Comparison of nutritional and immunological scoring systems predicting prognosis in T1-2N0 colorectal cancer.

Previous studies have shown that the new nutritional and immunological status scoring systems of the Naples prognostic score (NPS), controlling nutritional status score (CONUT), and the older prognostic nutritional index (PNI) are independent predictors in colorectal cancer. This study compares the prognostic value of NPS, CONUT, and PNI in T1-2N0 colorectal cancer. We retrospectively evaluated 305 consecutive stage I (T1-2N0M0) colorectal cancer patients who underwent radical surgery from January 2010 to December 2015 at our hospital. The NPS results were divided into 3 groups (0, 1, and 2 groups), and the PNI and CONUT results were divided into 2 groups (low and high groups). The patients with low PNI had worse overall survival (OS) and disease-free survival (DFS) than those with high PNI (P < 0.001 and P < 0.001, respectively). Multivariate analysis showed that PNI was independently associated with OS and DFS (P < 0.001 and P < 0.001, respectively), but NPS and CONUT results were not. The PNI is an independent predictor in stage I colorectal cancer, but NPS and CONUT results are not.

Soluble SIGLEC5: A New Prognosis Marker in Colorectal Cancer Patients.

Simple SummaryAmongst colorectal cancers, there is significant heterogeneity, which hinders the search for a single disease detection approach. Clinical prognostic markers are urgently needed. The aim of our prospective study was to analyse the possible role of pre-operative soluble SIGLEC5 plasma levels in patient prognosis and evolution. In a cohort of 114 patients with colorectal cancer, our data confirmed the relevance of soluble SIGLEC5 levels as a prognosis marker and exitus predictor. Altogether, our data indicate that levels of this protein could be a novel and promising biomarker for patients with colorectal cancer.Colorectal cancer (CRC) is the second most deadly and third most commonly diagnosed cancer worldwide. There is significant heterogeneity among patients with CRC, which hinders the search for a standard approach for the detection of this disease. Therefore, the identification of robust prognostic markers for patients with CRC represents an urgent clinical need. In search of such biomarkers, a total of 114 patients with colorectal cancer and 67 healthy participants were studied. Soluble SIGLEC5 (sSIGLEC5) levels were higher in plasma from patients with CRC compared with healthy volunteers. Additionally, sSIGLEC5 levels were higher in exitus than in survivors, and the receiver operating characteristic curve analysis revealed sSIGLEC5 to be an exitus predictor (area under the curve 0.853; cut-off > 412.6 ng/mL) in these patients. A Kaplan–Meier analysis showed that patients with high levels of sSIGLEC5 had significantly shorter overall survival (hazard ratio 15.68; 95% CI 4.571–53.81; p ≤ 0.0001) than those with lower sSIGLEC5 levels. Our study suggests that sSIGLEC5 is a soluble prognosis marker and exitus predictor in CRC.

INHBA is a novel mediator regulating cellular senescence and immune evasion in colorectal cancer.

Colorectal cancer (CRC) is one of the most mortal cancers in the world. Multiple factors and bio-processes are associated with in tumorigenesis and metastasis of CRC, including cellular senescence and immune evasion. This study aims to identify prognostic and immune-meditating effects of INHBA in CRC. Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) in senescent cells and CRC tissues from the Cancer Genome Atlas (TCGA). Key factor was settled from the alternative DEGs set. Enrichment analyses and functional networks prediction were determined from online databases. Correlation analyses were performed to reveal the association among key factor, immune infiltration, T cell biomarkers and immune checkpoints. Moreover, expressions of key factors and immune checkpoints of tissue and blood samples from CRC patients as well as human CRC cell lines were measured. Results showed that Inhibin beta A (INHBA) was sorted out as a senescence-related factor and a prognostic predictor in CRC. What's more, INHBA was found highly co-expressed with T-cell biomarkers and immune checkpoints. In conclusion, INHBA was considered as a senescence-related regulator and a prognostic predictor in CRC, which also mediating immune evasion.

PARASITIC ABSCESS AS AN INCIDENTAL HISTOLOGICAL FINDING IN THE TREATMENT OF SIGMOID COLON CANCER

Background: A high worldwide incidence of colorectal cancer defines the importance of search not only for effective treatment methods, but also for risk factors for the cancer development and its worst prognosis. The influence of many genetic factors, environmental characteristics and lifestyle features has already been proven, and recently the attention of researchers is being focused on the study of microbiota and, in particular, various parasitic intestinal diseases in the context of risk factors for colorectal cancer.Clinical case presentation: we demonstrate an incidental finding of parasitic invasion signs during the pathomorphological examination of the surgical specimen in a patient without an epidemiological history.Conclusion: Further studies are needed not only to confirm and substantiate the role of micro- and macroorganisms inhabiting the intestine in the development of oncological diseases, but also to identify individual links of pathogenesis, pathological pathways and signaling molecules involved in carcinogenesis. Research like this could help broaden knowledge about both the risk factors and predictors of colorectal cancer and the potential sites for targeted therapy.

Identification of prognostic immune-related signature predicting the overall survival for colorectal cancer.

The morbidity and mortality of patients with colorectal cancer, one of the most common malignant tumors worldwide, is steadily increasing. The aim of this study was to investigate the association between prognostic immune-related gene profile and the outcome of colorectal cancer in patients by analyzing datasets from The Cancer Genome Atlas (TCGA). Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) further demonstrated that these genes were enriched in many immune-related biological processes. Univariate Cox regression analysis was applied to examine the association of immune-related genes with the prognosis in patients with colorectal cancer. The least absolute shrinkage and selection operation (LASSO) Cox regression model was then used to establish the immune-related signature for the prognostic evaluation of colorectal cancer in patients. Survival differences were assessed by the Kaplan-Meier method along with the log-rank test. A total of 133 prognostic immune-related signatures were identified by using the univariate Cox proportional hazards regression analysis. A 14-gene signature-based risk score was constructed using the LASSO Cox regression. According to the cut-off of the risk-score, patients were assigned to the low-risk and high-risk groups. The log-rank test suggested that the survival time of the low-risk group was significantly higher than that of the high-risk group. In the time-dependent ROC curve analysis, the AUC for 1-year, 3-year, and 5-year overall survival (OS) were 0.781, 0.742, and 0.791, respectively. GO and KEGG analysis further revealed that the gene sets were actively involved in immune and inflammatory response, as well as the cytokine-cytokine receptor interaction pathway. To summarize, we identified a novel 14-gene immune-related signature that may potentially serve as a prognostic predictor for colorectal cancer, thereby contributing to patient personalized treatment decisions. Further research needs to be conducted to validate the prognostic value of the selected genes.

The prediction of colorectal cancer using anthropometric measures: A Swedish population-based cohort study with 22 years of follow-up.

Obesity is a risk factor for colorectal cancer (CRC). The objective of this article is to investigate whether anthropometric measures reflecting visceral obesity are better predictors of CRC than body mass index (BMI). Data were analysed from the Malmö Diet and Cancer study in Sweden, comprising 16,669 women and 10,805 men (median age 56.6 and 59.1 years) followed for a median 21.5 years. Diagnoses of CRC were identified using Swedish national registers. Cox regression was used to test the associations of BMI, waist circumference (WC), waist-hip ratio, waist-to-height ratio, waist-to-hip-to-height ratio, A Body Shape Index (ABSI) and percentage body fat with the development of CRC adjusted for age, alcohol consumption, smoking, education and physical activity in men and women. None of the measures were significantly associated with an increased risk for CRC in women. WC was the strongest predictor of colon cancer (CC) in men and the only measure that was independent of BMI. ABSI was the only measure significantly associated with the risk of rectal cancer in men. Visceral obesity, best expressed as WC, is a risk factor for CC in men but a poor predictive marker for CRC in women.

Patient-reported outcomes as predictors of survival in patients with bowel cancer: a systematic review.

The prognostic value of patient-reported outcomes (PROs) has been determined in some cancers, but a focussed review in colorectal cancer (CRC) has not yet been conducted. We systematically reviewed PRO predictors of CRC patient survival. We searched four electronic databases (from inception to May 2018), reference lists and professional organisations to identify studies reporting pre-treatment PRO predictors of overall survival (OS) or progression-free survival (PFS) in CRC identified through univariate or multivariate models. Two reviewers independently applied inclusion criteria and extracted data on study characteristics, median and 1-year survival rates, PROs assessed and model results. In 25 of 27 studies (n = 12,544), at least one PRO was significantly associated with survival. Physical functioning, fatigue, pain and appetite loss predicted OS more often than other PROs in metastatic disease (19/27 studies). One study explored PRO predictors in early-stage CRC, finding emotional well-being and mood predicted OS. In mixed-stage samples (7/27 studies), physical functioning predicted OS more often than other PROs. Few studies modelled PFS, for which few PROs had predictive value. Physical and psychological functioning, pain, fatigue and appetite loss had prognostic significance above and beyond clinical predictors in CRC. Routine monitoring of these PROs may allow earlier detection and amelioration of problems, which may improve quality of life and perhaps extend survival. More research is needed to determine prognostic value of PROs in early-stage CRC, and prognostic significance of changes in PRO scores.

Circulating long non-coding RNA colon cancer-associated transcript 2 protected by exosome as a potential biomarker for colorectal cancer

BackgroundColon cancer-associated transcript 2 (CCAT2) plays a crucial role in several cancers. However, the clinical significance of circulating CCAT2 expression in colorectal cancer (CRC) has not previously been elucidated. In this study, we aimed to elucidate the potential role of CCAT2 and its clinical significance of circulating expression level in CRC. MethodsWe detected the expression of CCAT2 in 75 pairs of tumorous and adjacent non-tumorous tissues derived from CRC patients by quantitative real-time polymerase chain reaction. The serum levels of CCAT2 expression were detected in an independent cohort of healthy controls and CRC patients. We analyzed the relationship between CCAT2 levels in serum and clinicopathological features of CRC patients. We also compared CCAT2 levels in paired pre-operative and post-operative serum samples. Furthermore, the existence of serum CCAT2 in exosomes was investigated. ResultsThe levels of CCAT2 expression were significantly over-expressed in tumor tissues (p < 0.05) compared to adjacent non-tumorous tissues. Higher CCAT2 expression was associated with advanced CRC patients. Moreover, the serum levels of CCAT2 expression were significantly over-expressed in CRC patients (p < 0.05) compared to those in healthy subjects. In addition, the CCAT2 levels were significantly decreased in post-operative samples than those in pre-operative ones (P = 0.01). We also found that CCAT2 expression was up-regulated in CRC exosomes (P < 0.001) and no significant differences of CCAT2 levels were found between in serum and in exosomes. ConclusionsOur data indicate that circulating CCAT2 which might protected by exosomes can serve as a novel potential predictor in CRC.

Overexpression of long noncoding RNA NORAD in colorectal cancer associates with tumor progression.

PurposeThe aim of this study was to elucidate the role and clinical significance of long noncoding RNA-activated by DNA damage (NORAD) in colorectal cancer (CRC).MethodsSixty pairs of tumorous and adjacent nontumorous tissues derived from CRC patients were subjected to quantitative real-time polymerase chain reaction to determine the expression level of NORAD. The serum levels of NORAD expression were also measured in an independent cohort of CRC patients as well as patients with benign diseases and healthy controls. Comparative analyses were performed to investigate the relationships between NORAD levels in tissues and clinicopathological features of CRC. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of NORAD in patients with CRC. Furthermore, the potential functions of NORAD in the development of CRC were explored in vitro, using the HCT116 and SW1116 CRC cell lines.ResultNORAD expression was significantly upregulated in the tumorous tissues of CRC patients (P<0.001) compared to the adjacent nontumorous tissues. Higher NORAD expression was associated with advanced CRC. Moreover, serum levels supported that NORAD could distinguish CRC patients from healthy controls and patients with benign diseases, indicating a potential diagnostic role in CRC. The ROC curve analysis showed a diagnostic efficacy with area under the curve of 0.800 (95% CI: 0.737–0.853). Mechanistic investigations indicated that NORAD silencing reduced CRC cell proliferation, migration, and invasion.ConclusionNORAD may serve as a novel predictor in CRC and may be a potential target for future therapy.

Biological functions and clinical significance of the newly identified long non‑coding RNA RP1‑85F18.6 in colorectal cancer.

The biological functions of long non-coding RNAs (lncRNAs) in cancer have not been fully elucidated. The present study demonstrated that the expression of a newly identified lncRNA, RP1-85F18.6, was upregulated in colorectal cancer (CRC) tissues and cell lines. Knockdown of lncRNA RP1-85F18.6 served a key role in tumor inhibition, reduced cell proliferation and invasion, disrupted the cell cycle, and increased apoptosis and pyroptosis of CRC cells. Conversely, overexpression of lncRNA RP1-85F18.6 exerted the opposite effects. Furthermore, silencing lncRNA RP1-85F18.6 decreased ΔNp63 expression at both the mRNA and protein levels. Furthermore, co-transfection with ΔNp63 siRNA and lncRNA RP1-85F18.6-expressing vector attenuated the tumor-promoting effects of lncRNA RP1-85F18.6 overexpression. The expression levels of lncRNA RP1-85F18.6, ΔNp63 and gasdermin D (GSDMD) were revealed to be associated with lymph node and distant metastases in patients with CRC, and therefore may serve as predictors in CRC. The findings of the present study suggested that lncRNA RP1-85F18.6 may trigger CRC cell proliferation, invasion and cell cycle disruption, and suppress apoptosis and pyroptosis of CRC cells through regulating ΔNp63 expression. Therefore, lncRNA RP1-85F18.6 and ΔNp63 may be considered unfavorable biomarkers, whereas GSDMD may be a favorable biomarker in CRC; these markers may prove valuable in the future diagnosis and prognosis of CRC.

Gene-Metabolite Interaction in the One Carbon Metabolism Pathway: Predictors of Colorectal Cancer in Multi-Ethnic Families.

For personalized healthcare, the purpose of this study was to examine the key genes and metabolites in the one-carbon metabolism (OCM) pathway and their interactions as predictors of colorectal cancer (CRC) in multi-ethnic families. In this proof-of-concept study, we included a total of 30 participants, 15 CRC cases and 15 matched family/friends representing major ethnic groups in southern California. Analytics based on supervised machine learning were applied, with the target variable being specified as cancer, including the ensemble method and generalized regression (GR) prediction. Elastic Net with Akaike’s Information Criterion with correction (AICc) and Leave-One-Out cross validation GR methods were used to validate the results for enhanced optimality, prediction, and reproducibility. The results revealed that despite some family members sharing genetic heritage, the CRC group had greater combined gene polymorphism-mutations than the family controls (p < 0.1) for five genes including MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G, and DHFR 19bp. Blood metabolites including homocysteine (7 µmol/L), methyl-folate (40 nmol/L) with total gene mutations (≥4); age (51 years) and vegetable intake (2 cups), and interactions of gene mutations and methylmalonic acid (MMA) (400 nmol/L) were significant predictors (all p < 0.0001) using the AICc. The results were validated by a 3% misclassification rate, AICc of 26, and >99% area under the receiver operating characteristic curve. These results point to the important roles of blood metabolites as potential markers in the prevention of CRC. Future intervention studies can be designed to target the ways to mitigate the enzyme-metabolite deficiencies in the OCM pathway to prevent cancer.

Personalized Nutrition-Genes, Diet, and Related Interactive Parameters as Predictors of Cancer in Multiethnic Colorectal Cancer Families.

To personalize nutrition, the purpose of this study was to examine five key genes in the folate metabolism pathway, and dietary parameters and related interactive parameters as predictors of colorectal cancer (CRC) by measuring the healthy eating index (HEI) in multiethnic families. The five genes included methylenetetrahydrofolate reductase (MTHFR) 677 and 1298, methionine synthase (MTR) 2756, methionine synthase reductase (MTRR 66), and dihydrofolate reductase (DHFR) 19bp, and they were used to compute a total gene mutation score. We included 53 families, 53 CRC patients and 53 paired family friend members of diverse population groups in Southern California. We measured multidimensional data using the ensemble bootstrap forest method to identify variables of importance within domains of genetic, demographic, and dietary parameters to achieve dimension reduction. We then constructed predictive generalized regression (GR) modeling with a supervised machine learning validation procedure with the target variable (cancer status) being specified to validate the results to allow enhanced prediction and reproducibility. The results showed that the CRC group had increased total gene mutation scores compared to the family members (p < 0.05). Using the Akaike’s information criterion and Leave-One-Out cross validation GR methods, the HEI was interactive with thiamine (vitamin B1), which is a new finding for the literature. The natural food sources for thiamine include whole grains, legumes, and some meats and fish which HEI scoring included as part of healthy portions (versus limiting portions on salt, saturated fat and empty calories). Additional predictors included age, as well as gender and the interaction of MTHFR 677 with overweight status (measured by body mass index) in predicting CRC, with the cancer group having more men and overweight cases. The HEI score was significant when split at the median score of 77 into greater or less scores, confirmed through the machine-learning recursive tree method and predictive modeling, although an HEI score of greater than 80 is the US national standard set value for a good diet. The HEI and healthy eating are modifiable factors for healthy living in relation to dietary parameters and cancer prevention, and they can be used for personalized nutrition in the precision-based healthcare era.

Type 2 diabetes and colorectal cancer survival: The multiethnic cohort.

This analysis examined type 2 diabetes (T2D) as a predictor of colorectal cancer (CRC) survival within the Multiethnic Cohort Study. Registry linkages in Hawaii and California identified 5,284 incident CRC cases. After exclusion of cases with pre-existing cancer diagnosis within 1 year and systemic disease, the analytic dataset had 3,913 cases with 1,800 all-cause and 678 CRC-specific deaths after a mean follow-up of 9.3 ± 5.2 years. Among CRC cases, 707 were diagnosed with T2D 8.9 ± 5.3 years before CRC. Cox regression with age as time metric was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for T2D status as predictor of CRC-specific and all-cause survival while adjusting for known confounders. Overall, CRC-specific survival was not associated with pre-existing T2D (HR = 0.84; 95% CI = 0.67-1.07). However, a significant interaction was seen for comorbidity (pinteraction =0.03) with better survival among those without pre-existing conditions (HR = 0.49; 95% CI = 0.25-0.96) while no association was seen in patients with comorbid conditions. All-cause mortality was also not related to pre-existing T2D (HR = 1.11; 95% CI = 0.98-1.27), but significantly elevated for individuals with T2D reporting comorbid conditions (HR = 1.36; 95% CI = 1.19-1.56). Stratification by T2D duration suggested higher CRC-specific and all-cause mortality among participants with a T2D history of ≥10 than <10 years. The findings were consistent across sex and ethnic subgroups. In contrast to previous reports, pre-existing T2D had no influence on disease-specific and all-cause survival among CRC patients. Only participants with additional comorbidity and possibly those with long T2D duration experienced higher mortality related to T2D.

Gene Environment Interactions and Predictors of Colorectal Cancer in Family-Based, Multi-Ethnic Groups.

For the personalization of polygenic/omics-based health care, the purpose of this study was to examine the gene–environment interactions and predictors of colorectal cancer (CRC) by including five key genes in the one-carbon metabolism pathways. In this proof-of-concept study, we included a total of 54 families and 108 participants, 54 CRC cases and 54 matched family friends representing four major racial ethnic groups in southern California (White, Asian, Hispanics, and Black). We used three phases of data analytics, including exploratory, family-based analyses adjusting for the dependence within the family for sharing genetic heritage, the ensemble method, and generalized regression models for predictive modeling with a machine learning validation procedure to validate the results for enhanced prediction and reproducibility. The results revealed that despite the family members sharing genetic heritage, the CRC group had greater combined gene polymorphism rates than the family controls (p < 0.05), on MTHFR C677T, MTR A2756G, MTRR A66G, and DHFR 19 bp except MTHFR A1298C. Four racial groups presented different polymorphism rates for four genes (all p < 0.05) except MTHFR A1298C. Following the ensemble method, the most influential factors were identified, and the best predictive models were generated by using the generalized regression models, with Akaike’s information criterion and leave-one-out cross validation methods. Body mass index (BMI) and gender were consistent predictors of CRC for both models when individual genes versus total polymorphism counts were used, and alcohol use was interactive with BMI status. Body mass index status was also interactive with both gender and MTHFR C677T gene polymorphism, and the exposure to environmental pollutants was an additional predictor. These results point to the important roles of environmental and modifiable factors in relation to gene–environment interactions in the prevention of CRC.

Prognostic value of multiple cytokine analysis in colorectal cancer: a systematic review.

The link between inflammation and outcome has been established in colorectal cancer through experimental evidence demonstrating an influential role of pro-inflammatory cytokines on tumour growth and progression. Furthermore, prognostic scores based on overall markers of systemic inflammation such as C-reactive protein and neutrophil count have been validated. Over recent years, an increasing number of inflammatory cytokines have been identified as prognostic predictors in colorectal cancer and the aim of this review was to evaluate the literature on the prognostic value of multiple cytokine measurement. The English language literature published since the year 2000 was searched using terms including, 'colorectal cancer', 'cytokines' and 'prognosis' through Medline, Embase and Scopus databases. Reports were screened by two independent reviewers and studies evaluating fewer than three cytokines were excluded. Quality assessments were performed in six domains before data extraction was undertaken in duplicate. Seven studies were found to evaluate multiple cytokines after 570 records were screened. The quality of these studies ranged from poor to moderate and were heterogeneous in terms of the patient population and the number and selection of cytokines tested. Four studies combined multiple cytokine levels into a single score and found them to be predictive of prognosis whereas the association between individual cytokines and outcome was not demonstrated consistently. The combination of multiple cytokine markers into a single prognostic score shows promise in colorectal cancer and further research is required to establish and validate such a score.

SHP2 associates with nuclear localization of STAT3: significance in progression and prognosis of colorectal cancer

Tyrosine phosphatase SHP2, encoded by PTPN11, has been implicated in many physiologic and pathologic processes in neoplastic progression. However, controversies are emerging from many studies, indicating SHP2 has a dual role in different types of tumors. We aimed to explore the role of SHP2 in progression and prognosis of colorectal cancer (CRC). SHP2 inhibited CRC cell proliferation and migration, and the phosphorylation of STAT3 was negatively regulated by SHP2 in CRC. SHP2 and nuclear STAT3 were examined in 270 CRC tissues. SHP2 was significantly correlated with nuclear STAT3 (Spearman’s rho = −0.408, P ≤ 0.001). Based on Cox regression analysis, patients with high levels of SHP2 and low levels of nuclear STAT3 had longer disease-specific survival (DSS) (HR, 0.362; 95% CI, 0.165–0.794) and disease-free survival (DFS) (HR, 0.447; 95% CI, 0.227–0.877). Further, low levels of SHP2 and high levels of nuclear STAT3 were independently associated with adverse outcomes in the whole cohort (DFS; HR, 2.353; 95% CI, 1.199–4.619). These results suggest that combination of SHP2 and nuclear STAT3 is a strong prognostic predictor in CRC.

Mitochondrial UQCRB as a new molecular prognostic biomarker of human colorectal cancer

Ubiquinol cytochrome c reductase binding protein (UQCRB) is important for mitochondrial complex III stability, electron transport, cellular oxygen sensing and angiogenesis. However, its potential as a prognostic marker in colorectal cancer (CRC) remains unclear. The aim of this study was to determine whether UQCRB can be used as a diagnostic molecular marker for CRC. The correlation between the expression of three genes (UQCRB, UQCRFS1 and MT-CYB) in the mitochondrial respiratory chain complex III and clinico-pathological features was determined. Compared to non-tumor tissues, UQCRB gene expression was upregulated in CRC tissues. Gene and protein expression of the genes were positively correlated. Copy number variation (CNV) differences in UQCRB were observed in CRC tissues (1.32-fold) compared to non-tumor tissues. The CNV of UQCRB in CRC tissues increased proportionally with gene expression and clinical stage. Single-nucleotide polymorphisms in the 3′-untranslated region of UQCRB (rs7836698 and rs10504961) were investigated, and the rs7836698 polymorphism was associated with CRC clinical stage. DNA methylation of the UQCRB promoter revealed that most CRC patients had high methylation levels (12/15 patients) in CRC tissues compared to non-tumor tissues. UQCRB overexpression and CNV gain were correlated with specific CRC clinico-pathological features, indicating clinical significance as a prognostic predictor in CRC. Gene structural factors may be more important than gene transcription repression factors with respect to DNA methylation in UQCRB overexpression. Our results provide novel insights into the critical role of UQCRB in regulating CRC, supporting UQCRB as a new candidate for the development of diagnostics for CRC patients.

Interferon-inducible CXC-chemokines are crucial immune modulators and survival predictors in colorectal cancer.

Tumor-infiltrating T-cells are strongly associated with prognosis in colorectal cancer, but the mechanisms governing intratumoral lymphocyte recruitment are unclear. We investigated the clinical relevance and functional contribution of interferon-regulated CXC-chemokines CXCL9, CXCL10, and CXCL11, described as T-cells attractants. Their expression was significantly elevated in tumors as compared to normal colon in 163 patients with colon cancer, represented an independent positive predictor of post-operative survival, and was highly significantly correlated with the presence of tumor-infiltrating cytotoxic CD8+ T-cells and CD4+ TH1-effector cells. The regulation of chemokine expression was investigated in established cell lines and in tissue explants from resected tumor specimen (n=22). All colorectal cancer cell lines tested, as well as stroma or endothelial cells, produced CXC-chemokines in response to cytokine stimulation. Moreover, resected tumor explants could be stimulated to produce CXC-chemokines, even in cases with initially low CXC-levels. Lastly, a causative role of chemokine expression was evaluated with an orthotopic mouse model, based on isogenic rectal CT26 cancer cells, engineered to express CXCL10. The orthotopic model demonstrated a protective and anti-metastatic role of intratumoral CXCL10 expression, mediated mainly by adaptive immunity.

The clinical use of the platelet/lymphocyte ratio and lymphocyte/monocyte ratio as prognostic predictors in colorectal cancer: a meta-analysis.

BackgroundConflicting evidence exists regarding the effects of platelet/lymphocyte ratio (PLR) and lymphocyte/monocyte ratio(LMR) on the prognosis of colorectal cancer (CRC) patients. This study aimed to evaluate the roles of the PLR and LMR in predicting the prognosis of CRC patients via meta-analysis.MethodsEligible studies were retrieved from the PubMed, Embase,andChina National Knowledge Infrastructure (CNKI) databases, supplemented by a manual search of references from retrieved articles. Pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated using the generic inverse variance and random-effect model to evaluate the association of PLR and LMR with prognostic variables in CRC, including overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS).ResultsThirty-three studies containing 15,404 patients met criteria for inclusion. Pooled analysis suggested that elevated PLR was associated with poorer OS (pooled HR = 1.57, 95% CI: 1.41 – 1.75, p< 0.00001, I2=26%) and DFS (pooled HR = 1.58, 95% CI: 1.31 – 1.92, p< 0.00001, I2=66%). Conversely, high LMR correlated with more favorable OS (pooled HR = 0.59, 95% CI: 0.50 – 0.68, p< 0.00001, I2=44%), CSS (pooled HR = 0.54, 95% CI: 0.40 – 0.72, p< 0.00001, I2=11%) and DFS (pooled HR = 0.82, 95% CI: 0.71– 0.94,p=0.005, I2=29%).ConclusionsElevated PLR was associated with poor prognosis, while high LMR correlated with more favorable outcomes in CRC patients. Pretreatment PLR and LMR could serve as prognostic predictors in CRC patients.