Prognosis Of Colorectal Carcinoma Research Articles

Fusobacterium Nucleatum Promotes Microsatellite Instability in Colorectal Carcinoma Through Up-regulation of miRNA-155-5p-Targeted Inhibition of MSH6 via the TLR4/NF-κB Signaling Pathway.

Fusobacterium nucleatum (Fn) is significantly associated with poor prognosis in colorectal carcinoma (CRC), however, mechanisms of Fn in DNA mismatch repair (MMR) and microsatellite instability (MSI) in CRC have not been fully elucidated. Clinical samples are collected to analyze the relationship between Fn abundance and microsatellite stability. Tumor cells are treated with Fn to detect the expression of proteins related to toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88), mutS homolog 6 (MSH6), and nuclear factor-κB (NF-κB) signaling pathways, respectively. Combined with the prediction results from TargetScan, the regulatory role of microRNA upstream of MSH6 is demonstrated. The effect of this regulatory axis on CRC development is demonstrated using a nude mouse tumor model. Compared with microsatellite stability (MSS)-type CRC patients, MSI-type showed higher Fn abundance. Fn treatment of CRC cells activated TLR4/Myd88/NF-κB signaling pathway, transcriptionally activating miRNA-155-5p expression, thereby negatively regulating MSH6. Fn treatment accelerated the malignant progression of CRC in mice, and this process is inhibited by miRNA-155-5p antagomir. Fn in CRC upregulated miRNA-155-5p by activating TLR4/NF-κB signaling to inhibit MSH6, and this regulatory pathway may affect MSS of cancer cells.

Prognostic Clinicopathological Parameters in Colorectal Carcinoma

Background: Colorectal carcinoma (CRC) is the third cause of cancer-related death worldwide Methods: This study aimed to assess the clinicopathological parameters and their correlation with prognosis in patients with colorectal carcinoma. Two hundred pathology reports for cases diagnosed with CRC in Doctor Soliman Fakeeh Hospital (DSFH) in the period 2000 to 2023 were retrieved from the archives and the Yasashi database of Fakeeh Hospital for reviewing the clinical and pathological data. Univariate & multivariate analyses were conducted. Results: A total of 50 reports were included in the study. In regard to the relation between clinicopathological findings and the prognosis of CRC, there was a statistically significant relation between grade of the tumor and its metastasis (p-value = 0.024). However, there was a statistically insignificant relationship to gender, age, diabetes mellitus status, neoadjuvant chemotherapy, surgical operation, location of the tumor, and invasion of the surrounding tissues. Conclusion: The study highlighted the significant correlation between clinicopathological findings, particularly the grade of the tumor, and the prognosis of colorectal carcinoma. Factors like tumor size, metastasis, and histological grade played crucial roles in determining the prognosis of CRC patients.

The Role of High Mobility Group Box B-1 in the Prognosis of Colorectal Cancer Based on the Changes in the Intestinal Mucosal Barrier.

Background: To investigate the expression of high mobility group box B-1 (HMGB-1) in patients with colorectal cancer (CRC) and its association with clinicopathological features and prognosis in colorectal carcinoma by combining bioinformatics and clinical data analysis, and to clarify the role of HMGB-1. To examine whether HMGB-1 expression is related to the damage of the intestinal mucosal barrier, and then explore the potential HMGB-1-dependent mechanisms affecting the progression of CRC. Methods: CRC datasets of GSE12945, GSE17536, and GSE17537 from the public gene chip database were screened and downloaded. Clinical information and CRC tissue samples from patients with stage I-III CRC from the hospital were collected. Serum samples of patients were applied by enzyme-linked immunosorbent assay on HMGB-1, and were divided into high and low HMGB-1 expression, which was examined by 16S rDNA sequencing. Immunohistochemistry was performed to examine the relationship between the expression of HMGB-1 and tight junction protein, occludin, tumor necrosis factor-α, and interferon-γ. Results: Based on the Cutoff value of 10.24 ng/mL, the CRC patients were divided into high and low expression groups. In the HMGB-1H patient group, the TNM staging, overall survival, disease-free survival, recurrence, and metastasis were inferior to the HMGB-1L group. The results of 16S rDNA sequencing demonstrated that the Providencia genus was found to be enriched in the HMGB-1L group. Immunohistochemical results showed that HMGB-1 expression was negatively correlated with the expression of ZO-1 and occludin (R = 0.035, R = 0.003, P < .05), but was positively correlated with the expression of TNF-α and IFN-γ (R = 0.016, R = 0.001, P < .05). Conclusion: The survival of CRC patients with positive HMGB-1 expression was significantly shortened, which may be related to the decrease of Rovitensis content, the decreased expression of ZO-1 and occludin, and the increased levels of TNF-α and IFN-γ, which in turn damage the intestinal mucosal barrier, leading to the development of CRC.

Grades of Poorly Differentiated Clusters are Associated with Lymph Node and the Tumour, Node and Metastasis Stages in Colorectal Carcinoma.

Colorectal carcinoma (CRC) is the third most common cancer globally. In Malaysia, CRC is most prevalent among males and the second most common cancer among females. The CRC arises mainly from the adenocarcinoma sequence. Poorly differentiated clusters (PDCs) and tumour budding (TB) are believed to represent sequential steps in tumour growth. Therefore, this study analysed the association between PDC grades with clinicopathological and demographic characteristics of CRC. A total of 47 CRC cases previously diagnosed by histopathological examination were reviewed for the presence of PDCs and graded accordingly. The association between PDC grades with clinicopathological and demographic characteristics was statistically analysed. Out of the 47 cases with PDCs, most of them were of grade 3 (G3) (n = 27, 57.4%), followed by grade 2 (G2) (n = 13, 27.7%) and grade 1 (G1) (n = 7, 14.9%). Higher PDC grades (G2 and G3) were mainly observed in higher tumour stage (T); T3 (n = 26, 83.9%), T4 (n = 12, 92.3%), N1 (n = 20, 86.9%), N2 (n = 15, 100%). In addition, there was a significant association between PDC grades with the nodal stage (N) (P = 0.013) and the tumour, node and metastasis (TNM) stages (P = 0.012). The PDC grades are useful for assessing the disease prognosis in CRC. A statistically significant association between PDC grades with N and TNM stages suggested that PDC grades are potential predictive parameters for invasive and metastatic risks in CRC.

Tumor-immune cell interaction and senescence-associated molecules in colorectal carcinoma

Cellular senescence permanently arrests the cell cycle of premalignant cells following protumorigenic stimuli, counteracting tumor progression. Senescence induction leads to phenotypic and metabolic changes and alters the interaction with the cells' microenvironment. This mediates tumor immunosurveillance but bears promalignant potential and may contribute to disease progression. Our study aims to investigate the prognostic potential of senescence markers in colorectal carcinoma (CRC) and to understand the interaction of senescent tumor cells and immune cells. Immunohistochemical markers were studied on atissue microarray (TMA) containing tumor tissue of n = 598 CRC patients and were evaluated using digital image analysis. Results were correlated with disease-specific survival (DSS) and progression-free survival (PFS). Consecutive TMA sections were stained for senescence markers and immune cell markers to analyze the spatial relation of those cell populations. Senescence was induced in CRC cell lines in vitro and co-cultures with various immune cell lines were established to study the interactions. Expression of different senescent-associated markers is associated with increased or decreased DSS and PFS. Close proximity of p21+ senescent tumor cells and CD8+ immune cells correlates with increased DSS and PFS. In vitro, senescent cells were dose-dependently eliminated by immune cells, which is facilitated via direct cell-cell contact and induction of apoptosis. Depicting the initiation of this important anti-tumor mechanism, markers of cellular senescence are of significant prognostic relevance in CRC. Moreover, our results show the pleiotropic effect of senescence in vivo. Absence as well as exceeding expression of senescence markers are associated with anegative prognosis in CRC. The impact of cellular senescence depends on the tumor microenvironment and the immunosurveillance of senescent cells. Proximity analyses of senescent cells and tumor-infiltrating immune cells have significant prognostic relevance and reflect this.

Expression of aquaporin 1, 3 and 5 in colorectal carcinoma: correlation with clinicopathological characteristics and prognosis.

Background: Prognostic biomarkers in colorectal carcinoma (CRC) have an important role in therapeutic strategy. Studies have shown that high expression of Aquaporin (AQP) is associated with poor prognosis in a variety of human tumors. AQP is involved in the initiation and development of CRC. The present study aimed to investigate the correlation between the expression of AQP1, 3 and 5 and clinicopathological features or prognosis in CRC. Methods: The AQP1, 3 and 5 expressions were analyzed based on the immunohistochemical staining of tissue microarray specimens including 112 patients with CRC between June 2006 and November 2008. The expression score of AQP (Allred_score and H_score) was digitally obtained with Qupath software. Patients were divided into high or low expression subgroups based on the optimal cut-off values. The relationship between expression of AQP and clinicopathological characteristics were evaluated using chi-square test, t-test, or one-way ANOVA, when appropriate. Survival analysis of 5-year progression free survival (PFS) and overall survival (OS) was performed with time-dependent ROC, Kaplan-Meier curves, univariate and multivariate COX analysis. Results: The AQP1, 3 and 5 expressions were associated with regional lymph node metastasis, histological grading, and tumor location in CRC, respectively (p < 0.05). Kaplan-Meier curves showed that patients with high AQP1 expression had worse 5-year PFS than those with low AQP1 expression (Allred_score: 47% vs. 72%, p = 0.015; H_score: 52% vs. 78% p = 0.006), as well as 5-year OS (Allred_score: 51% vs. 75%, p = 0.005; H_score: 56% vs. 80%, p = 0.002). Multivariate Cox regression analysis indicated that AQP1 expression was an independent risk prognostic factor (p = 0.033, HR = 2.274, HR95% CI: 1.069-4.836). There was no significant correlation between the expression of AQP3 and 5 and the prognosis. Conclusion: The AQP1, 3 and 5 expressions correlate with different clinicopathological characteristics and the AQP1 expression may be a potential biomarker of prognosis in CRC.

The Incidence and Prognosis Value of Perineural Invasion in Rectal Carcinoma: From Meta-Analyses and Real-World Clinical Pathological Features

AimsPerineural invasion (PNI) is a special type of metastasis of several cancers and has been reported as being a factor for poor prognosis in colorectal carcinoma. However, investigations of PNI in only rectal cancer and a comprehensive analysis combining meta-analyses with real-world case studies remain lacking. Materials and methodsFirst, articles from 2000 to 2020 concerning the relationship between PNI and rectal cancer prognoses and clinical features were meta-analysed. Subsequently, we carried out a retrospective analysis of 312 rectal cancer cases that underwent radical surgery in the real world. The incidence of PNI and the relationship between PNI and prognosis, as well as clinicopathological factors, were investigated. ResultsThe incidence of PNI was 23.09% and 33.01% in the meta-analysis and clinical cases, respectively. PNI occurred as early as stage I (2.94%). Moreover, neoadjuvant therapy significantly reduced the PNI-positive rate (20.34% versus 26.54%). Both meta-analysis and real-world clinical case studies suggested that PNI-positive patients had poorer prognoses than PNI-negative patients. We established an effective risk model consisting of T stage, differentiation and lymphovascular invasion to predict PNI in rectal cancer. ConclusionPNI is a poor prognostic factor for rectal cancer and could occur even in stage I. Additionally, neoadjuvant therapy could sufficiently reduce the PNI-positive rate. T stage, lymphovascular invasion and differentiation grade were independent risk factors for PNI and the risk model that included these factors could predict the probability of PNI.

Predictive value of intratumoral-metabolic heterogeneity derived from 18F-FDG PET/CT in distinguishing microsatellite instability status of colorectal carcinoma.

Microsatellite instability (MSI) status is a significant biomarker for the response to immune checkpoint inhibitors, response to 5-fluorouracil-based adjuvant chemotherapy, and prognosis in colorectal carcinoma (CRC). This study investigated the predictive value of intratumoral-metabolic heterogeneity (IMH) and conventional metabolic parameters derived from 18F-FDG PET/CT for MSI in patients with stage I-III CRC. This study was a retrospective analysis of 152 CRC patients with pathologically proven MSI who underwent 18F-FDG PET/CT examination from January 2016 to May 2022. Intratumoral-metabolic heterogeneity (including heterogeneity index [HI] and heterogeneity factor [HF]) and conventional metabolic parameters (standardized uptake value [SUV], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) of the primary lesions were determined. MTV and SUVmean were calculated on the basis of the percentage threshold of SUVs at 30%-70%. TLG, HI, and HF were obtained on the basis of the above corresponding thresholds. MSI was determined by immunohistochemical evaluation. Differences in clinicopathologic and various metabolic parameters between MSI-High (MSI-H) and microsatellite stability (MSS) groups were assessed. Potential risk factors for MSI were assessed by logistic regression analyses and used for construction of the mathematical model. Area under the curve (AUC) were used to evaluate the predictive ability of factors for MSI. This study included 88 patients with CRC in stages I-III, including 19 (21.6%) patients with MSI-H and 69 (78.4%) patients with MSS. Poor differentiation, mucinous component, and various metabolic parameters including MTV30%, MTV40%, MTV50%, and MTV60%, as well as HI50%, HI60%, HI70%, and HF in the MSI-H group were significantly higher than those in the MSS group (all P < 0.05). In multivariate logistic regression analyses, post-standardized HI60% by Z-score (P = 0.037, OR: 2.107) and mucinous component (P < 0.001, OR:11.394) were independently correlated with MSI. AUC of HI60% and our model of the HI60% + mucinous component was 0.685 and 0.850, respectively (P = 0.019), and the AUC of HI30% in predicting the mucinous component was 0.663. Intratumoral-metabolic heterogeneity derived from 18F-FDG PET/CT was higher in MSI-H CRC and predicted MSI in stage I-III CRC patients preoperatively. HI60% and mucinous component were independent risk factors for MSI. These findings provide new methods to predict the MSI and mucinous component for patients with CRC.

Cancer-Associated Fibroblast Risk Model for Prediction of Colorectal Carcinoma Prognosis and Therapeutic Responses.

Colorectal carcinoma (CRC) is a malignant tumor of the digestive system. Cancer-associated fibroblasts (CAFs) are important cellular elements in the tumor microenvironment of CRC, which contribute to CRC progression and immune escape. To predict the survival outcome and therapeutic responses of CRC patients, we identified genes connected with stromal CAF and generated a risk model. In this study, we used multiple algorithms to reveal CAF-related genes in the Gene Expression Omnibus and The Cancer Genome Atlas datasets and construct a risk model composed by prognostic CAF-associated genes. Then, we evaluated whether the risk score could predict CAF infiltrations and immunotherapy in CRC and confirmed the expression of the risk model in CAFs. Our results showed that CRC patients with high CAF infiltrations and stromal score had worse prognosis than those with low-CAF infiltrations and stromal score. We obtained 88 stromal CAF-associated hub-genes and generated a CAF risk model consisting of ZNF532 and COLEC12. Compared with low-risk group, the overall survival in high-risk group was shorter. The relationship between risk score, ZNF532 and COLEC12, and stromal CAF infiltrations and CAF markers was positive. In addition, the effect of immunotherapy in the high-risk group was not as good as that in the low-risk group. Patients with the high-risk group were enriched in chemokine signaling pathway, cytokine-cytokine receptor interaction, and focal adhesion. Finally, we confirmed that the expressions of ZNF532 and COLEC12 in risk model were widely distributed in fibroblasts of CRC, and the expression levels were higher in fibroblasts than CRC cells. In conclusion, the prognostic CAF signature of ZNF532 and COLEC12 can be applied not only to predict the prognosis of CRC patients but also to evaluate the immunotherapy response in CRC patients, and these findings provide the possibility for further development of individualized treatment for CRC.

Immunohistochemical Expression Profile of SATB2 in Colorectal Adenocarcinoma and Association with Clinicopathological Parameters

Introduction: Colorectal carcinoma is the third most common cancer worldwide. Several clinicopathological parameters act as prognostic factors in colorectal carcinoma, but only a few are helpful in predicting the treatment outcome. Therefore, there is a need for better prognostic markers which also aids in assessing treatment benefits in colorectal carcinoma patients. Special AT Rich Sequence Binding Protein 2 (SATB2) is a highly specific marker for colorectal tissue. Decreased expression of SATB2 is also associated with poor prognosis in colorectal carcinoma. Aim: To analyse the histomorphology, immunohistochemical expression profile of SATB2 and association with clinicopathological parameters in colorectal adenocarcinoma. Materials and Methods: The cross-sectional study included 84 cases of colorectal carcinoma received in the Department of Pathology, SRM Medical College Hospital and Research Centre, Kattankulathur, Chennai, Tamil Nadu, India, in the period between April 2021 to September 2022. Both biopsy and resected specimens were included in the study. Relevant clinical data was collected. Histological diagnosis, grading and staging of the tumour was done using Haematoxylin and Eosin (H&amp;E) slides as described and tabulated. Immunohistochemistry (IHC) for SATB2 and was done and expression profile compared with the clinicopathological parameters to assess prognostic significance. Data was analysed using software-Statistical Package for Social Sciences (SPSS, version 23.0). Results: Out of the 84 cases, 42 were biopsy and 42 resected specimens. Mean age of the patients in the study was 57.9 years. Patients were predominantly males (n=51, 60.7%) with a male:female ratio of 1.54:1. Of the 84 cases, 40.5% (n=34) had tumour located in the rectum. Majority of the cases were moderately differentiated adenocarcinoma (n=48, 57.1%). Predominantly, stage III tumours (n=33, 39.3%) were noted. Out of the tumours showing decreased expression of SATB2, 55% (n=22) were left-sided tumours, metastasis was seen in 60% (n=24 cases), 37.5% of cases (n=9) showed lymphovascular invasion, and 55% (n=22) had a stage III tumour. Conclusion: The present study results indicate that a decrease in SATB2 expression is associated with presence of lymphovascular invasion, perineural invasion, regional and distant metastasis and a higher pathological stage which signifies poor prognosis in colorectal carcinoma. These aid the physician for risk stratification of patients and enable personalised treatment choices including adjuvant chemotherapy in high-risk groups.

Evaluation of the associations between GDF-15, OPG, and IL-15 levels in CRC: preliminary results

Introduction: Osteoprotegerin (OPG), Interleukin-15 (IL-15), and Growth/Differentiation Factor-15 (GDF-15) are all proven to take part in the processes associated with colorectal carcinoma (CRC) including tissue remodeling, inflammation modulation, and metastasis. Aim of the study: To investigate the concentrations of GDF-15, OPG and IL-15 in tumor and margin tissues of CRC in relation to clinicopathological features of patients. Material and methods: The study used 50 specimens of tumor and tumor-free margin tissues obtained from CRC patients. To determine the GDF-15, OPG and IL-15 concentrations commercially available enzyme-linked immunosorbent assay (ELISA) kits were used. Results: Concentrations of GDF-15, OPG and IL-15 were significantly higher in the tumor in comparison with the margin. The tumor levels of GDF-15 were positively associated with those of OPG and IL-15, while tumor levels of OPG correlated positively with those of IL-15. There was no association between levels of investigated molecules and clinical features of patients. Conclusions: The levels of GDF-15, OPG and IL-15 are elevated in patients suffering from CRC. More studies are needed to establish a specific role of these cytokines in the development, tumor growth, progression, and prognosis of CRC and to examine their role as possible CRC treatment candidates.

What are the problems with the current staging of discontinuous tumour nodules (DTNs) in colorectal carcinoma? Is there a better way?

Discontinuous extramural tumour nodules (DTNs) are deposits of metastatic carcinoma in soft tissue not associated with lymph nodes. Although they are established as an adverse prognostic factor in colorectal carcinoma (CRC), under the AJCC eighth edition staging system their presence does not upstage patients who also have lymph node metastases. Counterintuitively, in some situations the presence of lymph node metastases may in effect downstage a patient with DTNs from pN1c to pN1a/b. Therefore, we sought to critically assess the significance of DTNs in a large unselected single institution cohort of patients undergoing surgical resection for CRC. Of 3822 CRC patients undergoing surgical resection from 2005 to 2021, DTNs were present in 686 (18.0%). In univariate (HR=2.687, 95CI 2.355-3.065; p<0.001) and multivariate analysis (HR=1.805, 95CI 1.529-2.132; p<0.001) in a model including age, gender, stage, grade, location, lymph node ratio and apical lymph node status, DTNs were associated with worse overall survival (OS). N1c patients (DTN present but no nodal metastasis) demonstrated worse OS compared to the current pN1a group (p<0.001) and were least different to the current pN2a group (p=0.571). Within the current N1a (p=0.013), N1b (p=0.004) and N2a (p=0.002) groups, patients who also had DTNs had worse OS. DTNs were associated with worse OS for all stage III CRCs combined (p<0.001), and for stage IIIB (p<0.001) and stage IIIC (p=0.007) individually. We conclude that DTNs are an independent adverse prognostic factor that should be considered in the staging system in a way that is additional to (rather than integrated with) the number of involved lymph nodes. We then assess a simple suggestion for how this could be achieved by increasing the overall stage by one group in the presence of DTNs (requiring the creation of a new stage IIID).

Colorectal Carcinoma in Children and Adolescents - Case Reports and Literature Review

Colorectal carcinoma (CRC) is extremely rare among pediatrics, particularly before puberty. It usually begins with nonspecific signs and symptoms, so the index of suspicion is low, consequently, the diagnosis may be delayed. Reports in the literature indicate that poor prognostic factors are more common in children than in adults, resulting in a worse outcome. Our objective is to report clinical profile, treatment and prognosis of CRC in children and adolescents admitted in our institution, and to perform a systematic review of reports in the bibliography.

Putative anoikis resistant subpopulations are enriched in lymph node metastases and indicate adverse prognosis in colorectal carcinoma

Anoikis refers to apoptosis induced by the loss of contact with the extracellular matrix. Anoikis resistance is essential for metastasis. We have recently shown that it is possible to quantitatively evaluate putative anoikis resistant (AR) subpopulations in colorectal carcinoma (CRC). Abundance of these multi-cell structures is an independent marker of adverse prognosis. Here, we have quantified putative AR subpopulations in lymph node (LN) metastases of CRC and evaluated their prognostic value and relationship with the characteristics of primary tumors. A case series included 137 unselected CRC patients, 54 with LN metastases. Areal densities (structures/mm2) of putative AR structures in primary tumors had been analyzed previously and now were determined from all nodal metastases (n = 183). Areal density of putative AR structures was higher in LN metastases than in primary tumors. Variation of the areal density within different LN metastases of a single patient was lower than between metastases of different patients. Abundance of putative AR structures in LN metastases was associated with shorter cancer specific survival (p = 0.013), and this association was independent of T and N stages. Abundance of putative AR structures in primary tumors and LN metastases had a cumulative adverse effect on prognosis. Enrichment of putative AR subpopulations in LN metastases suggest that in metastasis formation, there is a selection favoring cells capable of forming these structures. Higher intra-case constancy relative to inter-case variation suggests that such selection is stable in metastasis development. Our findings indirectly support the biological validity of our concept of putative AR structures.

Mucin phenotypes and clinicopathological features of colorectal adenocarcinomas: Correlation with colorectal adenocarcinoma with enteroblastic differentiation

BackgroundThe mucin phenotypes of colorectal carcinoma (CRC) is related to the biological behavior and prognosis. But there has been no studies evaluating phenotypic characteristics in a large number of cases. Furthermore, colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of CRC and having poor prognosis. The aims of this study were to clarify the correlation between mucin phenotypes and tumor development, including biological behavior in CRC, as well as to investigate characteristic of mucin phenotypes in CAED. Methods and results974 CRC cases and 42 CAED cases of CRCs were classified five types (large-intestinal, small-intestinal, gastric, mixed, and unclassified) of mucin phenotypes by using immunohistochemistry (IHC). IHC was performed on tissue microarrays with antibodies against followings: MUC2, MUC5AC, MUC6, and CD10. In CRCs, large-intestine type has a relatively better prognosis, small-intestinal type frequently shows venous invasions, and liver metastases, gastric type has more high-histological grades and lymphatic invasions, mixed type shows originating from the right side of the colon, larger tumor size and mucinous type, but less venous invasions and liver metastasis, whereas the unclassified type showed poorer prognosis in overall survival with statistical significance. The majority of CAED were found to be small-intestinal type or unclassified type. ConclusionsThe phenotypic classification is useful for predicting the prognosis of CRCs. Small-intestinal type and unclassified type showed dismal prognosis in CRCs. We speculate that CAED having aggressive behavior and poor prognosis might reflect characteristics of small-intestinal and unclassified types.

Characteristics of local and system immunity, and features of cancer stem cells in patients with different stage, dynamics and prognosis of colorectal carcinoma

Clinical prognosis in malignant tumors` is among the most challenging problems of contemporary medicine. It is thought to depend on both biologic properties of tumor cells and patients` immune status. The features of tumor cells and immune reactions are closely interrelated and mutually conditioned. Therefore, possible application of their characteristics as prognostic markers is of great fundamental and clinical importance. The aim of our study is to find out the most significant immune factors for prognosis of colorectal cancer (CRC) based on estimation of local and system immune factors, and some characteristics of tumor cells in the patients at various stages of the disease and different clinical course. Cellular factors of immunity and cytokines were studied in blood and tumor tissue of 299 patients with colorectal cancer (stages I-IV). Malignant cells expressing stem cell markers CSC), MHC and PDL-1 molecules were also counted in the tumor tissue. Blood samples were drawn prior to operation, and tissue samples were taken during surgery being the 1st line of treatment. Flow cytometry techniques (FCM), immunohistochemistry (IHC), and ELISA approach were employed. We have compared data on the patients at different CRC stages (with or without local and distant metastases), as well as cases with different course of the disease (evolving distant metastases and fatal outcome during period of observation). Our results demonstrated increased amounts of NK-cells and IL-6 concentration, along with decreased percentage of blood CD4+ cells in the patients with local metastases, as well as higher CSC numbers in malignant tissue. The initially generalized CRC cases with distant metastases were characterized by high levels of blood IL-6, monocytes and granulocytes responding to fMLF, while in tumor tissue elevated amounts of NKT, CSC and decreased expression of MHC and PDL-1 were observed on tumor cells, like as lower PD-1/ PDL-1 expression on tumor-infiltrating lymhocytes. Unfavorable CRC dynamics, i.e., metastasizing during the observation period was preceded by increased levels of IL-10 in blood, NK cells with poor cytotoxicity, monocytes and granulocytes responding to fMLF. In tumor tissue, overexpression of CSC markers and hypo-expression of MHC on tumor cells were noted. Fatal outcome was preceded by elevation of blood IL-6levels, tissue levels of NKТ and CSC percentages, along with decreased NK cells subset (CD16dimCD56bright) in blood, and decline of MHC-expressing cells in the tumor. Thus, high blood levels of IL-6 and IL-10, fMLF-responding monocytes and granulocytes, as well as elevated amounts of NKT and CSC, hypo-expression of MHC in tumor tissue could be considered prognostic markers of unfavorable course in CRC patients. Decrease of PD-1/PDL-1 expression on tumor cells and lymphocytes from its microenvironment in advanced CRC is of special attention, because checkpoint inhibitors are prescribed in such cases.

A CLINICOPATHOLOGICAL STUDY OF THE CORRELATION OF CARCINOEMBRYONIC ANTIGEN IN COLORECTAL CARCINOMA: IN A TERTIARY CARE MEDICAL COLLEGE SET-UP IN EASTERN INDIA

Introduction: Carcino embryonic antigen(CEA) is overexpressed primarily by adenocarcinomas including colon, rectum, breast and lung. It should be noted that more than 90% of primary colorectal carcinomas produce CEA.CEA is a classic tumour marker for CRC, which is used to monitor the recurrence of the disease and as a prognostic factor for the patients. In the present scenario, the serum CEAtest is recommended by the American Society of Clinical Oncology and the European Group on Tumor Markers 7 as a prognostic biomarker for recurrent CRC following curative resection. Aims: To study the distribution of carcinoembryonic antigen in colorectal carcinoma, the role of carcinoembryonic antigen in the prognosis of colorectal carcinoma, to the variability of carcinoembryonic antigen values in recurrence of colorectal carcinoma and the sensitivity and specicity of carcinoembryonic antigen estimation in colorectal cancer Material And Method: This Institution based observational and prospective study was all the adult patients(&gt;18yrs) who have been diagnosed clinically with colorectal carcinoma and with recurrent disease in the Department of General surgery of R.G.Kar medical college and hospital from January 2019 to August 2020 were included in this study. Result: 10% of the patients were in Duke stage A, 16% patients were Duke stage B; 40% patients were with Duke stage C and 34%patients were Duke stage D of colorectal carcinoma. Among those 13 patients with Duke A and B staging 30% had increased CEA, whereas among those 37 patients with Duke stage C and D 92% had increased CEA levels. The p-value was found to be 0.00033 that is&lt;0.05,which meant the test was statistically signicant. 80%(n=38) of the patients with colon carcinoma had increased CEAvalues whereas 20%(n=2) of the patients had normal CEAvalues. 77%(n=7) patients in the rectal carcinoma group had increased CEAlevels whereas in 23%(n=3) patients it was normal. Conclusion:This study shows an increased amount of CEAlevels in the preoperative period then the patient's chances of recurrence and metastasis increases, hence having a poor prognosis. Regular surveillance through serial monitoring of the CEAlevels in the postoperative period is essential to be vigilant of recurrences and metastasis, which may increase chances of mortality in the patient.

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Introduction: We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). Methods: CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. Results: Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. Conclusion: CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

AVL9 promotes colorectal carcinoma cell migration via regulating EGFR expression

BackgroundDespite advanced treatments could inhibit progression of colorectal carcinoma (CRC), the recurrence and metastasis remain challenging issues. Accumulating evidences implicated that AVL9 played a vital role in human cancers, but it’s biological function and mechanism in CRC remain unclear.AimTo investigate the biological role and mechanism of AVL9 in colorectal carcinoma.ResultsAVL9 expression was significantly upregulated in tumor tissues than that in matched normal tissues both at mRNA and protein levels. High expression of AVL9 was closely correlated with M status, stages and poor prognosis of colorectal carcinoma (CRC) patients. Functionally, AVL9 overexpression promoted cell migration rather than cell proliferation in vitro, whereas AVL9 knockdown exhibited the contrary results. Mechanistically, AVL9 regulated EGFR expression, and knockdown of EGFR restrained AVL9-induced cell migration.ConclusionThese findings demonstrated that AVL9 contributed to CRC cell migration by regulating EGFR expression, suggesting a potential biomarker and treatment target for CRC.

Identification of methyltransferase-like protein 11B as a new prognostic biomarker for colorectal cancer through an analysis of The Cancer Genome Atlas.

This study had the goal of investigating whether an association exists between the prognosis of patients with colorectal carcinoma (CRC) and the neutrophil-lymphocyte ratio/prealbumin ratio (NLR/PA) and methyltransferase-like protein 11B (METTL11B) expression. First, the differentially expressed gene METTL11B was screened in The Cancer Genome Atlas (TCGA) database, and the expression of METTL11B was verified in the GEPIA (Gene Expression Profiling Interactive Analysis) and TCGA databases. The clinical information of 100 patients who underwent CRC surgery at Jiangsu Cancer Hospital was retrospectively evaluated. Immunohistochemistry was used to further analyze METTL11B expression in CRC tissues from the patients. Patients were monitored for 3 years to assess survival. The Kaplan-Meier technique and log-rank test were employed for single-factor survival analysis; for multifactor analysis, the Cox regression approach was adopted. Nomograms were built for internal verification. METTL11B expression was higher in cancer tissues than in neighboring normal tissues. Significant differences were observed regarding body weight reduction, CA199, serum albumin, chemotherapy use, and the incidence of vascular cancer thrombus between the low and high METTL11B expression groups (all P<0.05). After 3 years of follow-up, 69 patients were alive and 31 patients had died, translating to a 31.0% mortality rate. The progression-free and overall survival of the low METTL11B expression and low NLR/PA groups were significantly superior to those of the high METTL11B expression and high NLR/PA groups, respectively (all P<0.05). Cox regression analysis revealed NLR/PA and METTL11B to be independent risk factors for CRC development, and tumor size and chemotherapy also had independent effects on CRC development. Our nomograms' c-index was 0.8493, indicating a reasonable accuracy of the prediction model. Increases in NLR/PA and METTL11B expression are linked to a poor prognosis of CRC. NLR/PA combined with METTL11B has a certain prognostic value for CRC. Moreover, METTL11B has the potential to be a new predictive biomarker and therapeutic target for individuals with this disease.