Characteristics Of Colorectal Cancer Patients Research Articles

Correlation of S100A4 and S100A14 Expression With Clinico-Pathological Features and Tumor Location in Colorectal Cancer Patients.

Background Colorectal cancer (CRC) remains a major cause of morbidity and mortality worldwide. Understanding the clinical and pathological characteristics of CRCpatients is essential for improving diagnosis, treatment, and prognostication. S100 proteins play a crucial role in CRC by promoting tumor growth, metastasis, and inflammation through their involvement in various cellular processes such as proliferation, migration, and immune response modulation. Elevated levels of specific S100 proteins have been associated with poor prognosis and serve as potential biomarkers for early detection and therapeutic targets in CRC. This study aims to analyze the general and medical characteristics of CRC patients, with a particular focus on the expression patterns of S100A4 and S100A14 proteins and their correlation with tumor location and various clinical parameters. Methods This cross-sectional study included 98 CRC patients aged 21 to 92 years. Clinical data were collected from Vajeen Hospital (Duhok/ Iraq), including age, gender, and presenting symptoms. Pathological data such as tumor site, tumor size, tumor, node, and metastasis (TNM) stage, tumor grade angio-lymphatic invasion, perineural invasion, and metastasis were analyzed. The expression of S100A4 and S100A14 proteins was assessed using immunohistochemistry, and their correlation with clinico-pathological features and tumor location was evaluated using statistical analysis. Results The 98 patients with a mean age of 57.27 years. The majority were over 50 years old (68, 69.39%) with a nearly equal gender distribution. The most common symptom was bleeding per rectum (36, 36.74%). TNM staging revealed 25.51% (n=25) of patients at stage I, 32.65% (n=32) at stage II, 24.49% (n=24) at stage III, and 17.35% (n=17) at stage IV. Angio-lymphatic invasion was present in 65.31% (n=64) of patients, and lymph node invasion in 38.78% (n=38). All tumors were adenocarcinomas, with 82.65% (n=81) being intermediate grade. S100A4 expression was low in early-stage tumors but significantly higher in advanced stages (P < 0.0001). High S100A4 expression was associated with vascular invasion (P = 0.0006), perineural invasion (P = 0.0002), lymph node invasion (P < 0.0001), and metastasis (P = 0.0010). S100A14 expression was inversely correlated with disease severity. Low S100A14 expression was more common in advanced stages (P < 0.0001) and was associated with higher rates of vascular invasion (P = 0.0018), lymph node invasion (P < 0.0001), and metastasis (P = 0.0001). Conclusion This study highlights significant correlations between S100A4 and S100A14 expression with various clinico-pathological features in CRC patients. High S100A4 expression is linked with tumor aggressiveness, whereas low S100A14 expression is associated with advanced disease stages and increased metastasis. However, there is no observed correlation between the expression of these proteins and the tumor site.

Gut microbiota characteristics of colorectal cancer patients in Hubei, China, and differences with cohorts from other Chinese regions.

The research on the correlation or causality between gut microbiota and the occurrence, development, and treatment of colorectal cancer (CRC) is receiving increasing emphasis. At the same time, the incidence and mortality of colorectal cancer vary among individuals and regions, as does the gut microbiota. In order to gain a better understanding of the characteristics of the gut microbiota in CRC patients and the differences between different regions, we initially compared the gut microbiota of 25 CRC patients and 26 healthy controls in the central region of China (Hubei Province) using 16S rRNA high-throughput sequencing technology. The results showed that Corynebacterium, Enterococcus, Lactobacillus, and Escherichia-Shigella were significantly enriched in CRC patients. In addition, we also compared the potential differences in functional pathways between the CRC group and the healthy control group using PICRUSt's functional prediction analysis. We then analyzed and compared it with five cohort studies from various regions of China, including Central, East, and Northeast China. We found that geographical factors may affect the composition of intestinal microbiota in CRC patients. The composition of intestinal microbiota is crucial information that influences colorectal cancer screening, early detection, and the prediction of CRC treatment outcomes. This emphasizes the importance of conducting research on CRC-related gut microbiota in various regions of China.

Epidemiological and clinicopathological characteristics of colorectal cancer patients in tertiary hospital in West Java

Problem consideredColorectal cancer (CRC) is the third most frequently diagnosed type of cancer in Indonesia, accounting for around 8.5% of cancer cases. This study aims to know the epidemiological and clinicopathological characteristics of CRC patients in Tertiary Hospital in West Java. MethodsThis study was a cross-sectional study. All the data were obtained from Hasan Sadikin General Hospital CRC Registry from November 2021 until May 2023. Results208 colorectal cancer patients were analyzed. The average age at diagnosis was 52,9 (52 ± 13.1) with 61% diagnosed over 50. More females (51%) were diagnosed. Smoking history included 37.5% active smokers and 41.8% passive exposure. Nutritionally, 65.8% were normal weight, 30.7% underweight, and 5% overweight. The most common presenting symptoms were constipation (49%) and rectal bleeding (38%). Stage III and IV were diagnosed in 77% of patients. Left-sided colon tumors (85%) were most frequent, with adenocarcinoma not otherwise specified (98%) being the dominant histology. Bowel obstruction (68%) was the most common complication. ConclusionCRC in Hasan Sadikin General Hospital was frequently diagnosed at a late stage, with a relatively high percentage of patients were below 50 years. Left-sided CRC and histological types of adenocarcinoma not otherwise specified were still the most common pathological features of CRC. Future research is needed to discover the potential multifactorial causes of this phenomenon.

Cancer-associated fibroblasts drive colorectal cancer cell progression through exosomal miR-20a-5p-mediated targeting of PTEN and stimulating interleukin-6 production.

This study evaluated the clinical relevance of a set of five serum-derived circulating microRNAs (miRNAs) in colorectal cancer (CRC). Additionally, we investigated the role of miR-20a-5p released by exosomes derived from cancer-associated fibroblasts (CAFs) in the context of CRC. The expression levels of five circulating serum-derived miRNAs (miR-20a-5p, miR-122-5p, miR-139-3p, miR-143-5p, and miR-193a-5p) were quantified by real-time quantitative PCR (RT-qPCR), and their associations with clinicopathological characteristics in CRC patients were assessed. The diagnostic accuracy of these miRNAs was determined through Receiver Operating Characteristic (ROC) curve analysis. CAFs and normal fibroblasts (NFs) were isolated from tissue samples, and subsequently, exosomes derived from these cells were isolated and meticulously characterized using electron microscopy and Western blotting. The cellular internalization of fluorescent-labeled exosomes was visualized by confocal microscopy. Gain- and loss-of-function experiments were conducted to elucidate the oncogenic role of miR-20a-5p transferred by exosomes derived from CAFs in CRC progression. The underlying mechanisms were uncovered through luciferase reporter assay, Western blotting, enzyme-linked immunosorbent assays, as well as proliferation and migration assays. The expression levels of serum-derived circulating miR-20a-5p and miR-122-5p were significantly higher in CRC and were positively correlated with advanced stages of tumorigenesis and lymph node metastasis (LNM). In contrast, circulating miR-139-3p, miR-143-5p, and miR-193a-5p were down-regulated in CRC and associated with early tumorigenesis. Except for miR-139-3p, they showed a negative correlation with LNM status. Among the candidate miRNAs, significantly elevated levels of miR-20a-5p were observed in both cellular and exosomal fractions of CAFs. Our findings indicated that miR-20a-5p induces the expression of EMT markers, partly by targeting PTEN. Exosomal miR-20a secreted by CAFs emerged as a key factor enhancing the proliferation and migration of CRC cells. The inhibition of miR-20a impaired the proliferative and migratory potential of CAF-derived exosomes in SW480 CRC cells, suggesting that the oncogenic effects of CAF-derived exosomes are mediated through the exosomal transfer of miR-20a. Furthermore, exosomes originating from CAFs induced increased nuclear translocation of the NF-kB p65 transcription factor in SW480 CRC cells, leading to increased interleukin-6 (IL-6) production. We established a set of five circulating miRNAs as a non-invasive biomarker for CRC diagnosis. Additionally, our findings shed light on the intricate mechanisms underpinning the oncogenic impacts of CAF-derived exosomes and underscore the pivotal role of miR-20a-5p in CRC progression.

Pathological Features of Colorectal Adenocarcinoma Patients Related to MLH1.

MLH1, one of the MMR proteins, is linked to DNA replication, its role being to repair the incorrect DNA sequences and to replace them with proper ones. The loss of the MLH1 gene expression is part of Lynch syndrome which can lead to a series of cancers like colorectal and endometrial ones. The aim of this paper is to correlate the levels of MLH1 in four different bio-logical fluids with clinicopathological features in colorectal cancer patients in order to predict them with high probability. Therefore, a mathematical model with given code in Matlab has been proposed to get the clinicopathological features with high probability by only introducing the values for MLH1 concentrations. All these data can be obtained in a very short time even before surgery which can be very helpful the surgeon and the oncologist. Four types of samples (whole blood, saliva, urine and tissue) were analyzed using stochastic microsensors; concentrations of MLH1 were determined and compared with different macroscopic and micro-scopic pathological features to obtain mathematical models for early, non-invasive diagnostic of colorectal adenocarcinoma. There have been established criteria and mathematical models for tumor location, TNM grading system, depth of the tumor, lymphatic, vascular and perineural invasions and the presence of mucus in the tumoral mass. By using whole blood, saliva and urine samples, the location can be approximated. The proposed mathematical models aimed to allow a minim/noninvasive characterization of the tumor and its location which can help the surgeon and the oncologist to choose faster the personalized treatment.

The Clinicopathological Correlation of KRAS Mutation and PTEN Expression Status in Primary and Metastatic Colorectal Carcinoma.

Colorectal cancer (CRC) researchhas identified a consistent loss of PTEN expression in both primary tumors and metastasis, highlighting its potential role in this disease. However, the impact of PTEN on downstream proteins of KRAS mutation, namely p-AKT, p-ERK, and p65 (NFkB), remains unknown. This study aims to explore the inhibitory effect of PTEN on KRAS downstream proteins and its correlation with pathological features in CRC patients. From January 1, 2015, to December 31, 2021, 86 CRC cases were collected from governmental and private laboratories in the Duhok province. Formalin-fixed, paraffin-embedded tissue blocks were obtained, and the study involved histopathological analysis, immunohistochemistry of PTEN, AKT, ERK, and P65 markers, and molecular analysis of the KRAS gene. Among the 86 cases, there were 46 males (53.5%) and 40 females (46.5%), with an equal distribution between right colon and left colon/rectum. Tumors larger than 5cm were observed in 47 cases, predominantly displaying a polypoid or ulcerated growth pattern. Most cases were moderately differentiated adenocarcinomas, with stages II and III being the most prevalent 31 cases (36%) and 34 cases (39.5%) respectively. Significant associations were found between PTEN, ERK expressions, and tumor location in the right colon (P=0.031 and P=0.009 respectively). Tumor size correlated with P65 expression (P=0.042). KRAS mutation showed a positive relationship with the type of tumor growth (P=0.035). Tumor grade increased with KRAS mutations (P=0.043). PTEN expression correlated significantly with ERK and AKT markers (P=0.018 and 0.035 respectively). P65 exhibited an association with KRAS mutation (P=0.034). The study revealed PTEN expression in association with the inhibition of AKT and ERK, and the absence of KRAS gene mutation. Conversely, PTEN is not expressed with the positively reactive P65 and the presence of KRAS mutation. This study contributes valuable insights into the complex interplay between PTEN expression, KRAS mutation, and downstream signaling pathways in CRC. It suggests potential avenues for further research and therapeutic strategies in the context of CRC treatment.

Association of Fusobacterium nucleatum infection with the clinicopathological characteristics in colorectal cancer patients.

Colorectal cancer (CRC) is a global health problem. The gut microbiome is now recognized as an important underlying factor to the initiation and progression of CRC. Fusobacterium nucleatum (FN) is one of the most studied bacteria in the aetiology of CRC. This study provided cohort evidence on the association of FN infection with clinicopathologic features in CRC patients. We analysed the cancerous and adjacent non-cancerous formalin-fixed paraffin embedded (FFPE) tissue of 83 CRC patients from a single medical centre in Malaysia. TaqMan probe-based qPCR targeting the 16S rRNA gene was used to detect the presence of FN in the extracted FFPE DNA. The differences in FN expression between cancer and non-cancer tissues were evaluated. Association studies between FN infection in the tumour and relative FN abundance with available clinical data were conducted. FN was more abundant in the cancerous tissue compared to non-cancerous tissue (p = 0.0025). FN infection in the tumour was significantly associated with lymph node metastasis (p = 0.047) and cancer staging (p = 0.032), but not with other clinicopathologic variables. In double-positive patients where FN was detected in both cancerous and non-cancerous tissue, the expression fold-change of FN, calculated using 2-ΔΔCT formula, was significantly higher in patients with tumour size equal to or greater than 5cm (p = 0.033) and in KRAS-mutated patients (p = 0.046). FN is enriched in CRC tumour tissue and is associated with tumour size, lymph node metastasis, cancer staging, and KRAS mutation in this single-centre small cohort study.

Association between different types of preoperative anemia and tumor characteristics, systemic inflammation, and survival in colorectal cancer.

Patients with colorectal cancer often have anemia and other symptoms after diagnosis, especially in patients with advanced colorectal cancer. This study explored the association between different types of preoperative anemia and tumor characteristics and inflammatory response in patients with colorectal cancer and to evaluate the prognosis of patients with different types of anemia before operation. The clinical data of 95 patients with colorectal cancer treated in the Fourth Hospital of Hebei Medical University from February 2016 to January 2018 were retrospectively analyzed. According to the hemoglobin concentration (Hb), mean corpuscular volume (MCV), mean hemoglobin content (MCH) and mean hemoglobin concentration (MCHC), the patients were divided into the non-anemia group, normal cell anemia group, and small cell anemia group. The three groups' general data, oncological characteristics, and mGPS scores were compared. The patients were followed up for five years, and the survival analysis was carried out. The cox proportional hazard regression model was used to analyze the prognostic factors of patients with colorectal cancer. The preoperative anemia rate of patients with colorectal cancer was 43.15% (41/95). There were significant differences in gender, weight loss, CA724, tumor location, tumor size, TNM stage, mGPS score, and positive expression rate of Ki-67 among different anemia groups. There was a significant difference in survival time among a non-anemia group, small cell anemia group, and normal cell anemia group (P<0.05). Multivariate analysis showed that tumor size, TNM stage, distant metastasis, mGPS score, Ki-67 positive expression rate, and anemia type were independent risk factors affecting the prognosis of colorectal cancer patients (P<0.05). The oncological characteristics of colorectal cancer patients with different types of preoperative anemia are different. Preoperative anemia and systemic inflammatory status are independent risk factors for the prognosis of colorectal cancer patients.

LncRNA VLDLR-AS1 Gene Expression in Colorectal Cancer in Patients from East Azerbaijan Province, Iran

Background: Colorectal cancer (CRC) is the third most common cancer that frequently spreads to other parts of the body, with a low chance of recovery and a high mortality rate. Long non-coding RNAs are considered significant prognostic and diagnostic indicators because they are dysregulated in various cancers and have distinctive expression patterns and high tissue- and cell-specificity. VLDLR-AS1 lncRNA deregulation has been associated with several malignancies. Objectives: This study aimed to evaluate the expression levels of VLDLR-AS1 in CRC. It was the first time this assessment was conducted. Methods: We studied 188 samples, including 94 tumor samples and 94 paired adjacent non-tumor tissues. Total RNA was extracted, and its quantity and purity were assessed. TaKaRa PrimeScript 1st Strand cDNA Synthesis Kit (Kusatsu, Japan) was used for the reaction. The StepOnePlus Real-Time PCR System (Applied Biosystems) was set up to assess the relative expression of VLDLR-AS1. Results: According to the qRT-PCR data, the VLDLR-AS1 expression levels in CRC tissues were significantly lower than in tumor margins (P &lt; 0.0001). In addition, receiver operating characteristic curve analysis demonstrated that VLDLR-AS1 expression can discriminate between tumor and non-tumor samples with the sensitivity and specificity of 72.34% and 51.06%, respectively (P = 0.03, AUC = 0.6274). However, no significant association was found between the expression levels of VLDLR-AS1 and clinicopathological features in CRC patients. Conclusions: The results of this study indicated that VLDLR-AS1 lncRNA is significantly downregulated in the tumor tissues of CRC patients compared to healthy tumor margin tissues. This evidence shows the potential of this gene as a promising biomarker for the early detection of CRC development.

High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer

BackgroundAs a phosphorylated protein, NOLC1 is mainly located in the nucleus and is highly expressed in a variety of tumors, participating in the regulation of cell proliferation and aging. This study further investigated the role of NOLC1 in colorectal cancer tumors, aiming to provide sufficient scientific evidence for the clinical treatment of colorectal cancer.MethodsWe used TCGA, GEO, TNMplot, GEPIA, and other databases to explore the expression level of NOLC1 in colorectal cancer patients, as well as the correlation between the clinical characteristics of colorectal cancer patients and their expression, and conducted the prognostic analysis. Immunohistofluorescence (IHF) staining verified the analytical results. Subsequently, KEGG and GO enrichment analysis was used to identify the potential molecular mechanism of NOLC1 promoting the occurrence and development of colorectal cancer. The influence of NOLC1 expression on the immune microenvironment of colorectal cancer patients was further investigated using the TIMER database. GDSC database analysis was used to screen out possible anti-colorectal cancer drugs against NOLC1. Finally, we demonstrated the effect of NOLC1 on the activity and migration of colorectal cancer cells by Edu Cell proliferation assay and Wound Healing assay in vitro.ResultsOur results suggest that NOLC1 is overexpressed in colorectal cancer, and that overexpression of NOLC1 is associated with relevant clinical features. NOLC1, as an independent risk factor affecting the prognosis of colorectal cancer patients, can lead to a poor prognosis of colorectal cancer. In addition, NOLC1 may be associated with MCM10, HELLS, NOC3L, and other genes through participating in Wnt signaling pathways and jointly regulate the occurrence and development of colorectal cancer under the influence of the tumor microenvironment and many other influencing factors. Related to NOLC1: Selumetinib, Imatinib, and targeted drugs such as Lapatinib have potential value in the clinical application of colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells.ConclusionsHigh expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells. Further studies and clinical trials are needed to confirm the role of NOLC1 in the development and progression of colorectal cancer.

Association Between Microsatellite Instability (MSI) based on MLH1 and PMS2 Marker with Clinicopathological Features of Colorectal Cancer Patients

Background: Microsatellite instability (MSI) is one of the important pathways involved in development of colorectal cancer (CRC). MSI occurs due to mutations or hypermethylation of negative MMR proteins MLH1 and PMS2. The accumulation of mutations at microsatellite locus accelerated the development of CRC. Characteristics of CRC patients with MSI are not sensitive to 5FU chemotherapy and have a good clinical outcomes that can be used as a prognostic factor and a predictor of therapy. Therefore MSI detection is needed. Method: A retrospective cross-sectional study of 80 CRC slides obtained from DR. Sardjito Hospital Yogyakarta and clinical laboratory in 2010-2016. Immunohistochemical staining with anti-MLH1 and anti PMS2 antibodies to see MSI status. Negative MLH1 expression is called MSI MLH1 positive and PMS2 negative expression is called positive MSI PMS2. The association between MSI MLH1 and PMS2 with clinicopathology parameters was analyzed using Chi square. Results: Colorectal cancer patients MSI MLH1 as much as 44 (61.1%), MSI PMS2 as much as 21 (29.2%) and, MSI MLH1 and PMS2 simultaneously as much as 18 (25.0%). MSI MLH1 and PMS2 positive are found in ≥50 years old. The number of male patients is more than women. Most of the patients had a T3-T4 tumor size with advanced stage and well differentiated. MSI MLH1 associated with tumor differentiation (p = 0.011). Conclusion: MSI MLH1 is associated with tumor differentiation (p = 0.011), but, no association with the other clinicopathology parameters. MSI PMS2 is not associated to the overall clinicopathology parameters. MSI MLH1 and PMS2 are not simultaneously associated with all clinicopathology parameters (p&gt; 0.05)

Genetic and immunologic characteristics of colorectal cancer patients with KRAS mutations and predictive significance of tumor immune microenvironment in adjuvant chemotherapy

Genetic and immunologic characteristics of colorectal cancer patients with KRAS mutations and predictive significance of tumor immune microenvironment in adjuvant chemotherapy

Association Between BsmI Vitamin D Receptor Gene Polymorphism and Clinicopathological Features of Colorectal Cancer Patients in 2019-2020 at Prof. Dr. I.G.N.G Ngoerah Denpasar Bali

Aging is related to the occurrence of cancer. Colorectal cancer is one of the most common types of cancer found in Indonesia. The BsmI vitamin D receptor polymorphism has been extensively studied before and has been associated with colorectal cancer. This study aims to determine the relationship between the BsmI vitamin D receptor polymorphism and the clinicopathological features of colorectal cancer patients in 2019-2020 at Prof. dr. I.G.N.G Ngoerah Denpasar Bali. This research is a cross-sectional analytical research. The study was conducted at the Biomedical Laboratory Unit of the Faculty of Medicine, Udayana University from June to December 2022. A total of 35 samples were obtained from stored biological materials of colorectal cancer patients who were treated at the Digestive Surgery Polyclinic at Prof. RSUP. dr. I.G.N.G Ngoerah in 2019-2020 in the Udayana University Biochemistry laboratory. To detect the status of the BsmI polymorphism, DNA segments were amplified by the polymerase chain reaction (PCR) method and followed by sequencing. The results showed from 35 samples, 8 samples (22.9%) had the GG allele and 27 samples (77.1%) had the GA allele. A statistically significant association was found between BsmI vitamin D receptor polymorphisms and colorectal cancer grading (p=0.016), but no significant association was found between BsmI vitamin D receptor polymorphisms and the histopathological type of colorectal cancer (p=0.553). The conclusion of this study is that there is a significant relationship between BsmI vitamin D receptor polymorphism and grading, but not with the histopathological type of colorectal cancer, age and gender of colorectal cancer patients in 2019-2020 at Prof. dr. I.G.N.G Ngoerah Denpasar Bali. Keywords: Colorectal cancer, Vitamin D receptor, BsmI polymorphism, clinicopathology.

Relationship Between Age and Depth of Invasion and Histopathological Features in Colorectal Cancer Patients in the Anatomical Pathology Department of Cut Meutia General Hospital (RSUCM) 2018 - 2021

Colorectal cancer has become one of the most common and most diagnosed cancers in the world, with as many as 1.4 million new cases being discovered each year. This cancer affects many elderly patients, but not a few young patients also experience it. Depth of invasion and type of histopathological appearance are the determining factors in determining the prognosis of colorectal cancer. The purpose of this study was to determine the relationship between age and depth of invasion and histopathological features in patients with colorectal carcinoma in the anatomical pathology section of RSU Cut Meutia, North Aceh for the 2018-2021 period. This research is a retrospective analytic study using the approach cross sectional study and use data taken from the results of laboratory examinations. Anatomical Pathology during the 2018-2021 period. The results of the study found that cancer that had invaded the subserosa to the peri-colorectal tissue (T3) and invaded other organs and/or perforated visceral peritoneum (T4) had a higher percentage in the age group.≤54 years, but statistically no significant relationship was found. Description adenocarcinoma is the most common histopathological appearance and has a higher percentage in the age group≤54 years, but statistically no significant relationship was found. So it can be concluded that there is no significant relationship between age and depth of invasion and the histopathological appearance of colorectal cancer patients

Correlation between clinical characteristics of colorectal cancer and nutritional status in patients undergoing surgery

Background: The incidence of colorectal cancer in Indonesia reaches 12.8 per 100,000 adult population and is the cause of 9.5% of cancer deaths. 40–80% of all colorectal cancer patients are malnourished. This study aims to determine the prevalence of nutritional status in colorectal cancer and the correlation between clinical characteristics of colorectal cancer and nutritional status in patients undergoing surgery. Methods: This research is an observational study with a cross sectional method. The reachable population of this study was colorectal cancer patients who underwent surgery at dr. Cipto Mangunkusumo Hospital, Jakarta and admission will occur from September-December 2022 with predetermined inclusion and exclusion criteria. The instrument used is the Mini Nutritional Assessment (MNA)—bivariate data analysis using Chi-square followed by a multivariate logistic regression test. Results: There were 71 patients diagnosed with colorectal cancer at RSUPN dr. Cipto Mangunkusumo, in the September-December 2022 period, will undergo surgery. Clinical characteristics of colorectal cancer patients showed that most patients were 64-78 years old (57.7%) and male (52.1%). For clinical stages, it can be seen that the majority of patients have stages III and IV (78.9%), with a large tumor mass of 1-10.9 cm (76.1%), and the location of the cancer is in the rectum (59.2%) ). The results of CA19-9 levels show that most patients with normal CA19-9 levels (62.0%) and CEA levels were increased (66.2%). While the nutritional status of colorectal cancer, most of them have at risk of being malnourished (52.1%), followed by having malnourished (43.7%). The bivariate test results showed that the tumor size was significant (p &lt;0.05). Conclusion: Most colorectal cancers are at risk of malnourished and there is a statistically strongest correlation between tumor mass and nutritional status in patients undergoing surgery.

Tumor deposits are associated with a higher risk of peritoneal disease in non-metastatic colorectal cancer patients.

Tumor deposit (TD) is a poor prognostic factor in colorectal cancer (CRC) patients. This study aimed to determine whether TD carry the same risk of peritoneal recurrence as known high-risk (HR) features in CRC patients. A retrospective cohort-study of stage I-III CRC patients from 2010 to 2015 was conducted. TD group was defined by the presence of TD on histopathology whereas HR group was defined by the presence of obstruction, perforation, or T4-stage. A total of 151 patients with CRC were identified, of which 50 had TD and 101 had a HR feature. The overall risk of peritoneal recurrence was higher in the TD group versus HR group (36.0% vs. 19.8%, p = 0.03). The risk of peritoneum as the site of first recurrence was also higher in the TD group (22.0% vs. 12.9%, p = 0.03). Overall cancer recurrence at any site was also higher in the TD group (56.0% vs. 34.7%, p = 0.01). Median time to first recurrence was 1.2 (0.7-1.9) years in the TD group compared to 1.4 (0.8-2.1) years in the HR group (p = 0.31). In non-metastatic CRC patients, TD might have a higher risk of tumor recurrence versus their HRcounterparts. Alternative strategies for surveillance and treatment should be considered.

The structure of pathogenic germline variants in colorectal cancer in Moscow patients

Describe the structure of pathogenic germline variants and clinical and anatomical features in colorectal cancer patients in Moscow. The whole genome sequencing results of patients with suspected hereditary cancer syndrome were evaluated. All identified genetic variants were validated using Sanger sequencing. The study included 238 patients with colorectal cancer, 41/238 (17.2%) patients have pathogenic germline variants associated with hereditary cancer syndromes or increased cancer risk. Lynch syndrome accounts for 8% of all colorectal cancer cases (19/238), and familial adenomatous polyposis - 1.7% (4/238). 5 new genetic variants were described for the first time in a Russian colorectal cancer patients: MLH1 c.1921dup (p.Leu641fs), APC c.2929C>T (p.Gln977Ter), PMS2 c.327del (p.Ala110LeufsTer2), MSH2 c.1857dup (p. Val620CysfsTer24), ATM c.895G>T (p.Glu299Ter). In 197 of 238 patients, no significant variants were identified or variants with an uncertain clinical underlying cause were identified. According to the results of the study, an earlier manifestation of a malignant neoplasm and a more frequent occurrence of high-grade carcinomas in the presence of pathogenic germline mutations were noted compared to the group of patients without clinically significant varianrs, while in the group with identified mutations, the frequency of regional and distant metastasis was not increased.

KCNE4 expression is correlated with the pathological characteristics of colorectal cancer patients and associated with the radioresistance of cancer cells.

Colorectal cancer (CRC) is a common malignancy, and radioresistance limits the effectiveness of radiotherapy for rectal cancer. This study is performed to investigate the role and regulatory mechanism of Potassium Voltage-Gated Channel Subfamily E Regulatory Subunit 4 (KCNE4) in the radioresistance of CRC cells. Immunohistochemical staining results of KCNE4 in normal tissues and CRC tissues were obtained from the Human Protein Atlas (HPA) database. The UALCAN database was used for analyzing KCNE4 mRNA expression in normal tissue samples and CRC tissue samples and its relationship with tumor stage. The relationship of KCNE4 expression with prognosis was analyzed utilizing the data of GEPIA database. LinkedOmics database was searched to analyze the co-expressed gene sets of KCNE4 in CRC, and to analyze the signaling pathways related with KCNE4 in CRC. GO and KEGG enrichment analyses were carried out on the co-expressed genes of KCNE4 with DAVID database. Ionizing radiation (IR)-resistant cell lines (HCT116/IR and HT29/IR) were established; cell viability was assessed via cell counting kit-8 (CCK-8) and EdU assays, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was performed for detecting cell apoptosis. Western blotting was carried out to detect the expressions of p-p85 and p-AKT. KCNE4 was highly expressed in CRC tissues and linked to advanced tumor stage, lymph node metastasis and poor prognosis of CRC patients. KCNE4 overexpression promoted HCT116/IR cell proliferation and inhibited the apoptosis, while KCNE4 knockdown suppressed HT29/IR cell proliferation and facilitated the apoptosis. Furthermore, high KCNE4 expression was associated with the activation of the PI3K/AKT signal pathway. KCNE4 is associated with the clinicopathological characteristics of CRC patients, and its high expression level contributes to the radioresistance of cancer cells via activating the PI3K/AKT signal pathway.

The prognostic index of m7G-related genes in CRC correlates with immune infiltration.

N7-methyladenosine (m7G) modifications have been the subject of growing research interest with respect to their relationship with the progression and treatment of various cancers. This analysis was designed to examine the association between m7G-related gene expression and colorectal cancer (CRC) patient outcomes. Initial training analyses were performed using the TCGA dataset, with the GSE28722 dataset then being used to validate these results. Univariate Cox analyses were initially conducted to screen out prognostic m7G-related genes, after which a LASSO approach was used to construct an m7G risk score (MRS) model. Kaplan-Meier curves, ROC curves, and Cox analyses were subsequently used to validate the prognostic utility of this model in CRC patients. The R maftools package was further employed to assess mutational characteristics in CRC patients in different MRS subgroups, while the ESTIMATE, CIBERSORT, and ssGSEA tools were used to conduct immune infiltration analyses. A WGCNA was then performed to identify key immune-associated hub genes. The EIF4E3, GEMIN5, and NCBP2 genes were used to establish the MRS model. Patients with high MRS scores exhibited worse overall survival than patients with low scores. In Cox analyses, MRS scores were independently associated with CRC patient prognosis. Patients with low MRS scores exhibited a higher tumor mutational burden and higher levels of microsatellite instability. In immune infiltration analyses, higher immune checkpoint expression and greater immune cell infiltration were also observed in patients with low MRS scores. WGCNA analyses further identified 25 CD8+ T cell infiltration-associated genes. These findings suggest that MRS values represent a useful biomarker capable of differentiating among CRC patients with different immunological features and prognostic outcomes, offering an opportunity to better determine which patients are likely to benefit from immune checkpoint inhibitor treatment.

Clinical Significance of Somatic Mutations in RAS/RAF/MAPK Signaling Pathway in Moroccan and North African Colorectal Cancer Patients.

Mutations in RAS (KRAS, NRAS) and BRAF genes are the main biomarker predicting response to anti-EGFR monoclonal antibodies in targeted therapy in colorectal cancer (CRC). Our study aims to evaluate the frequencies of KRAS, NRAS and BRAF mutations and their possible associations with clinico-pathological features in CRC patients from Morocco. DNA was extracted from 80 FFPE samples using the QIAamp DNA FFPE-kit. RAS and BRAF mutations were assessed by pyrosequencing assays using Qiagen, KRAS Pyro®kit 24.V1, Ras-Extension Pyro®kit 24.V1 and BRAF Pyro®Kit 24.V1, respectively, and carried out in the PyroMark-Q24. RAS mutations were identified in 57.5% (56.2% in KRAS, 8.8% in NRAS). In KRAS gene, exon 2 mutations accounted for 93.3% (68.9% in codon 12, 24.4% in codon 13). Within codon 12, G12D was the most prevalent mutation (37.7%), followed by G12C (13.4%), G12S (8.9%) and G12V (6.6%). Within codon 13, the most frequently observed mutation was G13D (22.3%). The mutation rates of exon 3 and 4 were 15.6% and 13.3%, respectively. In exon 3 codon 61, 2.3% patients were detected with two concurrent mutations (Q61R, Q61H), and 4.4% with three concurrent mutations (Q61R, Q61H, Q61L). In NRAS gene, the mutation rates of exon 2, 3 and 4 were 57.1%, 28.6%, and 14.3%, respectively. G13A and Q61H were the most common mutations, accounting for 42.9% and 28.5%, respectively. There were 13% patients with concurrent KRAS/NRAS mutation and 4.3% wt KRAS with NRAS mutations. No mutations were identified in BRAF gene. In both sexes, KRAS codon 12 mutations were associated with higher stage III/IV tumors. Moreover, Patients whose tumor is in the proximal colon (56.3%) are more likely to harbor KRAS mutations than those tumor located in rectum (25%). RAS mutations could be useful in future target anti-EGFR therapy and molecular CRC screening strategy in Morocco.