Metastasis Of Colorectal Carcinoma Research Articles

Hawthorn Proanthocyanidin Extract Inhibits Colorectal Carcinoma Metastasis by Targeting the Epithelial-Mesenchymal Transition Process and Wnt/β-Catenin Signaling Pathway.

Colorectal carcinoma (CRC) is a major global health concern, with cancer metastasis being the main cause of patient mortality, and current CRC treatments are challenged by drug resistance. Although natural compounds, especially in foods like hawthorn proanthocyanidin extract (HPOE), have good anticancer activity, their effects on CRC metastasis remain unknown. Therefore, our objective was to investigate the impact and potential mechanisms of HPOE on the movement and infiltration of cells in the HCT116 CRC cells. Firstly, scratch-healing experiments confirmed the anti-migratory and anti-invasive capabilities of HPOE. Then, network pharmacology identified 16 possible targets, including MMP-9. Subsequently, RT-qPCR and Western blotting experiments confirmed that HPOE downregulated epithelial-mesenchymal transition-related factors (N-cadherin and MMP-9) and inhibited Wnt/β-catenin pathway activation. Finally, these results were experimentally validated using the Wnt pathway activator Licl and inhibitor XAV939. It was confirmed that HPOE had a certain inhibitory effect on the activation of the Wnt signaling pathway caused by the activator Licl and could enhance the inhibitory effect of the inhibitor XAV939. Our findings provide a basis for developing functional foods or dietary supplements, especially positioning HPOE as a functional food raw material for adjuvant treatment of CRC, given its ability to inhibit metastasis through the Wnt/β-catenin pathway.

Novel high-resolution contrast agent ultrasound techniques HiFR CEUS and SR CEUS in combination with shear wave elastography, fat assessment and viscosity of liver parenchymal changes and tumors.

The continuous development of ultrasound techniques increasingly enables better description and visualization of unclear lesions. New ultrasound systems must be evaluated with regard to all these diagnostic possibilities. A multifrequency C1-7 convex probe (SC7-1M) with the new high-end system Resona A20 Series was used. Modern technologies, including HiFR CEUS, SR CEUS and multimodal tissue imaging with shear wave elastography (SWE), fat evaluation and viscosity measurements (M-Ref) were applied. Of n = 70 (mean value 48,3 years±20,3 years, range 18-84 years) cases examined, a definitive diagnosis could be made in n = 67 cases, confirmed by reference imaging and/or follow-up. Of these, n = 22 cases were malignant changes (HCC (hepatocellular carcinoma) n = 9, CCC (cholangiocellular carcinoma) n = 3, metastases of colorectal carcinomas or recurrences of HCC n = 10). In all 12 cases of HCC or CCC, the elastography measurements using the shear wave technique (with values >2 m/s to 3.7 m/s) showed mean values of 2.3±0.31 m/s and a degree of fibrosis of F2 to F4. In n = 14 cases, changes in the fat measurement (range 0.51 to 0.72 dB/cm/MHz, mean values 0.58±0.12 dB/cm/MHz) in the sense of proportional fatty changes in the liver were detected. In the 4 cases of localized fat distribution disorders, the values were >0.7 dB/cm/MHz in the sense of significant fatty deposits in the remaining liver tissue. Relevant changes in the viscosity measurements with values >1.8 kPa were found in n = 31 cases, in n = 5 cases of cystic lesions with partially sclerosing cholangitis, in n = 13 cases of malignant lesions and in n = 9 cases post-interventionally, but also in n = 4 cases of benign foci with additional systemic inflammation. The results are promising and show a new quality of ultrasound-based liver diagnostics. However, there is a need for further investigations with regard to the individual aspects, preferably on a multi-center basis.

Potential for Metastasis and Recurrence in Colorectal Carcinoma In Situ: A Retrospective Analysis of 1069 Patients

BackgroundColorectal carcinoma in situ, characterized by cancer limited to the intramucosal layer or known as intraepithelial carcinoma, has conventionally considered to be without any risk of regional lymph node metastasis. However, isolated cases of regional lymph node metastasis, local recurrence, and distant metastasis challenge this assumption. This study aimed to assess the occurrence of regional lymph node metastasis and recurrence of colorectal carcinoma in situ. MethodsA retrospective analysis was conducted in 1069 patients who underwent full-thickness local excision or radical surgery for colorectal carcinoma in situ between January 1994 and December 2020. Histopathological features were assessed by 2 experienced pathologists. In cases of suspected recurrence, evaluation involved abdomen-pelvis and chest computed tomography, or PET-CT. ResultsThe recurrence rate of colorectal carcinoma in situ patients was 0.46%. Among the patients, 9 were diagnosed with regional lymph node metastasis or cancer recurrence. Of these, 4 patients were diagnosed with lymph node metastasis during primary surgery; 2 exhibited regional lymph node metastasis, and 2 presented with both regional and distant lymph node metastases. Regional lymph node metastasis occurred in additional 2 patients after radical surgery for the primary tumor. Distant metastasis was observed in 3 patients: hepatic metastasis in 1, hepatic and pulmonary metastases in another, and small bowel metastasis in the third patient. Among the 5 patients experiencing cancer recurrence, 1 expired due to cancer progression. ConclusionContrary to previous assumptions, colorectal carcinoma in situ can potentially metastasize to lymph nodes and recur. Therefore, careful assessment at the time of diagnosis is crucial, recognizing the possibility of lymph node metastasis or recurrence. This approach is essential for accurately identifying instances of cancer recurrence and ensuring optimal oncological outcomes.

Association of Tumour Budding With Histological Type And Grade, Pathological Stage And Lymph Node Metastasis In Colorectal Carcinoma

Association of Tumour Budding With Histological Type And Grade, Pathological Stage And Lymph Node Metastasis In Colorectal Carcinoma

Prognostic potential of MNX1-AS1 in chemotherapy of colorectal carcinoma.

To clarify the role of MNX1-AS1 in 5-FU resistance of Colorectal carcinoma (CRC). Relative levels of MNX1-AS1 in CRC and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Recruited CRC patients were treated by 5-FU-based FOLFOX chemotherapy, and they were divided to effective group and non-effective group according to the therapeutic efficacy, followed by comparison of their differences in clinical indicators. Influences of MNX1-AS1 on clinical features of CRC were analyzed. In addition, in vitro level of MNX1-AS1 in 5-FU-resistant HCT-8 cells and their parental cells was detected. After knockdown of MNX1-AS1 in HCT-8/5-FU cells, viability change was evaluated by cell counting kit-8 (CCK-8) assay. At last, regulatory effects of MNX1-AS1 on expression levels of ABC family genes were detected. MNX1-AS1 was upregulated in CRC tissues than paracancerous ones, and its level was higher in 5-FU-resistant CRC cases in comparison to 5-FU-sensitive cases. MNX1-AS1 level was linked to tumor size, tumor differentiation, depth of invasion, TNM staging and lymphatic metastasis in CRC. Notably, TNM staging, depth of invasion and lymphatic metastasis could affect the efficacy of FOLFOX chemotherapy in CRC patients. Knockdown of MNX1-AS1 reduced viability in HCT-8/5-FU cells, and downregulated ABCA1, ABCB1, ABCC1, ABCG1 and ABCG2. MNX1-AS1 triggers 5-FU resistance in CRC cells. Knockdown of MNXK1-AS1 is conductive to the well response to FOLFOX chemotherapy in CRC patients.

DPY30 promotes colorectal carcinoma metastasis by upregulating ZEB1 transcriptional expression

DPY30 belongs to the core subunit of components of the histone lysine methyltransferase complex, which is implicated in tumorigenesis, cell senescence, and other biological events. However, its contribution to colorectal carcinoma (CRC) progression and metastasis has yet to be elucidated. Therefore, this study aimed to investigate the biological function of DPY30 in CRC metastasis both in vitro and in vivo. Herein, our results revealed that DPY30 overexpression is significantly positively correlated with positive lymph nodes, epithelial-mesenchymal transition (EMT), and CRC metastasis. Moreover, DPY30 knockdown in HT29 and SW480 cells markedly decreased EMT progression, as well as the migratory and invasive abilities of CRC cells in vitro and lung tumor metastasis in vivo. Mechanistically, DPY30 increased histone H3K4me3 level and promoted EMT and CRC metastasis by upregulating the transcriptional expression of ZEB1. Taken together, our findings indicate that DPY30 may serve as a therapeutic target and prognostic marker for CRC.Graphical

Bcl-xL mediates interferon-beta secretion by protease-activated receptor 2 deficiency through the mitochondrial permeability transition pore in colorectal cancer metastasis

Cellular plasticity and immune escape are synergistic drivers of tumor colonization in metastatic organs. Activation of protease-activated receptor 2 (PAR2) signaling promotes metastasis of colorectal carcinoma (CRC). The role of PAR2 in regulating the immune microenvironment and cancer progression remains unclear. We demonstrated that the regulation of liver metastasis by PAR2 requires a competent immune system. PAR2 knockdown enhanced liver infiltration of activated CD8+ T cells prior to metastatic foci formation in an interferon receptor-dependent manner. PAR2 depletion increased interferon (IFN)-β production via the cGAS-STING and RIG-1 pathways. PAR2 inhibition increased mitochondrial permeability and cytosolic accumulation of mitochondrial DNA, which was reversed by Bcl-xL expression. Strikingly, shRNA against PAR2 with an immune checkpoint blocker (ICB) acted synergistically to suppress liver metastasis. Analysis of single-cell sequence data and 24 paired samples confirmed the regulatory effect of PAR2 on the metastatic immune environment in human CRC. Therefore, PAR2 signaling is involved in stabilizing the mitochondrial membrane and regulating the immune microenvironment through IFN-β during liver metastasis in CRC. The synergistic effect of the PAR2 inhibitor and ICB provides a potential therapeutic strategy for metastatic CRC treatment.

SEMA3B-AS1 suppresses colorectal carcinoma progression by inhibiting Semaphorin 3B-dependent VEGF signaling pathway activation.

Mounting evidence has demonstrated the considerable regulatory effects of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of various carcinomas. LncRNA Semaphorin 3B (SEMA3B) antisense RNA 1 (SEMA3B-AS1) has been found to be dysregulated in a few carcinomas recently. However, its potential function and mechanism in colorectal carcinoma (CRC) have not yet been examined. Here we show that SEMA3B-AS1 acts as a crucial regulator of CRC progression. We found that SEMA3B-AS1 expression was downregulated in CRC cell lines and tissues. Downregulation of SEMA3B-AS1 was significantly associated with poor survival in CRC patients. Overexpression of SEMA3B-AS1 reduced the cell growth and metastasis of CRC in vivo and in vitro. In addition, SEMA3B-AS1 promoted the expression of its sense-cognate gene SEMA3B, a member of the Semaphorin family (SEMAs), by recruiting EP300 to induce H3K9 acetylation at the SEMA3B promoter. Furthermore, we proved that SEMA3B-AS1 suppressed CRC angiogenesis by affecting the vascular endothelial growth factor signaling pathway activation which was regulated by the SEMA3B-NRP1 axis. Our work unravels a novel mechanism of SEMA3B-AS1 in the inhibition of CRC malignant progression and highlights its probability as a new promising diagnostic marker and therapeutic target for CRC interventions.

Fusobacterium nucleatum-triggered neutrophil extracellular traps facilitate colorectal carcinoma progression

BackgroundFusobacterium nucleatum (Fn) acts as a procarcinogenic bacterium in colorectal carcinoma (CRC) by regulating the inflammatory tumor microenvironment (TME). Neutrophil extracellular traps (NETs), which can be generated by persistent inflammation, have been recently considered to be significant contributors in promoting cancer progression. However, whether NETs are implicated in Fn-related carcinogenesis is still poorly characterized. Here, we explored the role of NETs in Fn-related CRC as well as their potential clinical significance.MethodsFn was measured in tissue specimens and feces samples from CRC patients. The expression of NET markers were also detected in tissue specimens, freshly isolated neutrophils and blood serum from CRC patients, and the correlation of circulating NETs levels with Fn was evaluated. Cell-based experiments were conducted to investigate the mechanism by which Fn modulates NETs formation. In addition, we clarified the functional mechanism of Fn-induced NETs on the growth and metastasis of CRC in vitro and in vivo experiments.ResultsTissue and blood samples from CRC patients, particularly those from Fn-infected CRC patients, exhibited greater neutrophil infiltration and higher NETs levels. Fn infection induced abundant NETs production in in vitro studies. Subsequently, we demonstrated that Fn-induced NETs indirectly accelerated malignant tumor growth through angiopoiesis, and facilitated tumor metastasis, as manifested by epithelial-mesenchymal transition (EMT)-related cell migration, matrix metalloproteinase (MMP)-mediated basement membrane protein degradation, and trapping of CRC cells. Mechanistically, the Toll-like receptor (TLR4)-reactive oxygen species (ROS) signaling pathway and NOD-like receptor (NOD1/2)-dependent signaling were responsible for Fn-stimulated NETs formation. More importantly, circulating NETs combined with carcinoembryonic antigen (CEA) could predict CRC occurrence and metastasis, with areas under the ROC curves (AUCs) of 0.92 and 0.85, respectively.ConclusionsOur findings indicated that Fn-induced NETs abundance by activating TLR4-ROS and NOD1/2 signalings in neutrophils facilitated CRC progression. The combination of circulating NETs and CEA was identified as a novel screening strategy for predicting CRC occurrence and metastasis.

PGC-1α promotes colorectal carcinoma metastasis through regulating ABCA1 transcription.

Colorectal cancer (CRC) is a highly aggressive cancer in which metastasis plays a key role. However, the mechanisms underlying metastasis have not been fully elucidated. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), a regulator of mitochondrial function, has been reported as a complicated factor in cancer. In this study, we found that PGC-1α was highly expressed in CRC tissues and was positively correlated with lymph node and liver metastasis. Subsequently, PGC-1α knockdown was shown to inhibit CRC growth and metastasis in both in vitro and in vivo studies. Transcriptomic analysis revealed that PGC-1α regulated ATP-binding cassette transporter 1 (ABCA1) mediated cholesterol efflux. Mechanistically, PGC-1α interacted with YY1 to promote ABCA1 transcription, resulting in cholesterol efflux, which subsequently promoted CRC metastasis through epithelial-to-mesenchymal transition (EMT). In addition, the study identified the natural compound isoliquiritigenin (ISL) as an inhibitor that targeted ABCA1 and significantly reduced CRC metastasis induced by PGC-1α. Overall, this study sheds light on how PGC-1α promotes CRC metastasis by regulating ABCA1-mediated cholesterol efflux, providing a basis for further research to inhibit CRC metastasis.

Ras-Related Protein Rap1A Accelerates the Malignant Process of Colorectal Carcinoma via Activating Fibroblast Growth Factor-2

We investigated the expression and clinical significance of Rap1A in colorectal carcinoma (CRC) progression and its association with FGF2 signaling. We measured Rap1A levels in 44 CRC tissues and adjacent non-tumoral tissues and analyzed clinical indicators in recruited patients. Knockdown of Rap1A in HCT-8 and SW480 cells was performed, followed by functional experiments to assess proliferative, migratory, and invasive abilities. The regulatory effects of Rap1A on FGF2 signaling by measuring protein levels of FGF2, ERK, and JNK. The binding interaction between Rap1A and FGF2 was explored using a dual-luciferase reporter assay. Rap1A, a protein highly expressed in CRC tissues, has been implicated in CRC progression and metastasis. Through various experiments, we demonstrated the involvement of FGF2 signaling in Rap1A-mediated CRC progression. Knockdown of Rap1A resulted in decreased proliferation, migration, and invasion of CRC cells, accompanied by downregulation of FGF2, ERK, and JNK proteins. FGF2, identified as a target gene of Rap1A, was found to be upregulated in CRC tissues. Overexpression of FGF2 counteracted the inhibitory effects of Rap1A knockdown on CRC cell abilities. In a mouse model, Rap1A knockdown inhibited CRC growth, which was rescued by FGF2 overexpression. In summary, Rap1A is highly expressed in CRC, predicts metastasis, and promotes CRC cell abilities through activation of FGF2 signaling.

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.

Use of iTRAQ-based quantitative proteomic identification of CHGA and UCHL1 correlated with lymph node metastasis in colorectal carcinoma.

Metastatic dissemination of colorectal cancer (CRC), the third most common cancer type, is responsible for CRC deaths. Understanding the transition of lymph node metastasis (LNM) from Stage II to Stage III is beneficial in the prognosis and intervention of CRC. In this study, a quantitative proteomic survey was conducted to investigate the LNM-associated proteins and evaluate the clinicopathological characteristics of these target proteins in CRC. By using the LC-MS/MS iTRAQ technology, we analysed the proteomic changes between LMN II and LMN III. Fresh tumours from the CRC specimens consisting of 12 node-negative (Stage II) and 12 node-positive (Stage III) cases were analysed by LC-MS/MS iTRAQ proteome analysis. Subsequently, tissue microarray with immunohistochemistry staining was conducted to access the clinicopathological characteristics of these proteins in 116 paraffin-embedded CRC samples, each for non-LNM and LNM CRC. To study the effects of the differentially expressed proteins on the potential mechanism, Boyden chamber assay, flow cytometry and shRNA-based assessments were conducted to examine the role of the epithelial-mesenchymal transition (EMT) and the invasiveness of CRC cells and others in vivo xenograft mouse model experiments. Forty-eight proteins were found differentially expressed between non-LNM and LNM CRC tissues. Protein abundances of chromogranin-A (CHGA) and ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) were observed in node-positive CRC (p < 0.05). Knockdown of CHGA and UCHL1 significantly regulate cancer behaviours of HCT-116, including inhibition of cell migration, invasiveness, cell cycle G1/S arrest and reactive oxygen species (ROS) generation. Mechanistically, the CHGA and UCHL1 inactivation displayed decreased levels of UCH-L1, chromogranin A, β-catenin, cyclin E, twist-1/2, vimentin, MMP-9, N-cadherin and PCNA through the activation of the Rho-GTPase/AKT/NFκB pathways. Histone modification of H3K4 trimethylation of CHGA and UCHL1 promoter were increased to activate their transcription through the signalling transduction such as Rho-GTPase, AKT and NFκB pathways. Our results indicated that UCHL1 and chromogranin A are novel regulators in CRC lymph node metastasis to potentially provide new insights into the mechanism of CRC progression and serve as biomarkers for CRC diagnosis at the metastatic stage.

PLOD2 promotes colorectal cancer progression by stabilizing USP15 to activate the AKT/mTOR signaling pathway.

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) has been reported as an oncogenic gene, affecting various malignant tumors, including endometrial carcinoma, osteosarcoma, and gastric cancer. These effects are mostly due to the enhanced deposition of collagen precursors. However, more studies need to be conducted on how its lysyl hydroxylase function affects cancers like colorectal carcinoma (CRC). Our present results showed that PLOD2 expression was elevated in CRC, and its higher expression was associated with poorer survival. Overexpression of PLOD2 also facilitated CRC proliferation, invasion, and metastasis in vitro and in vivo. In addition, PLOD2 interacted with USP15 by stabilizing it in the cytoplasm and then activated the phosphorylation of AKT/mTOR, thereby promoting CRC progression. Meanwhile, minoxidil was demonstrated to downregulate the expression of PLOD2 and suppress USP15, and the phosphorylation of AKT/mTOR. Our study reveals that PLOD2 plays an oncogenic role in colorectal carcinoma, upregulating USP15 and subsequently activating the AKT/mTOR pathway.

The Role and Significance of Hepatic Environmental Cells in Tumor Metastatic Colonization to Liver

Metastasis, a main cause of death in tumor patients, is a complicated process that involves multiple steps, presenting a major clinical challenge. Tumor cells break the physical boundaries of a primary tumor, intravasate into the lumina of blood vessels, travel around through blood circulation, extravasate into distant organs, colonize the host organs, and eventually develop into the foci of metastatic cancer. The metastasis of tumor cells exhibits organ-tropism, i.e., tumor cells preferentially spread to specific organs. Liver is a common site for metastasis. The pattern of metastasis in uveal melanoma, colorectal carcinoma, and pancreatic ductal adenocarcinoma shows organ-tropism for liver. The anatomical structure of liver determines its hemodynamic characteristics, e.g., low pressure and slow blood flow, which tend to facilitate the stasis and colonization of tumor cells in the liver. Besides the hemodynamic features, the metastatic colonization of liver depends largely on the interaction between tumor cells and the hepatic microenvironment (especially liver-resident cellular components). Resident cells of the hepatic microenvironment include hepatocytes, liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), Kupffer cells (KCs), etc. Herein, we discussed the role and significance of liver-resident cells in the metastatic colonization of tumor in the liver.

Low PD-L1 expression in immune cells predicts the presence of nodal metastasis in early invasive (pT1) colorectal cancer: a novel tool to tailor surgical treatment.

The current criteria for surgical treatment after endoscopic resection of a pT1 colorectal carcinoma (CRC) are unsatisfactory because nodal involvement is rarely present. This study investigates the correlation between PD-L1 expression and nodal metastasis in pT1 CRCs to enable its use for tailoring surgical treatment after endoscopic removal. Histopathological features of 81 surgically resected pT1 CRC, 19 metastatic and 62 non-metastatic cases were assessed. PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and independently assessed by two pathologists using tumour proportion score (TPS), combined positive score (CPS) and immune cell score (ICS). The correlation between PD-L1 expression and nodal metastasis, the optimal cut-off values, interobserver agreement and impact upon patients' surgical management were determined. PD-L1 expression in termsof CPS and ICS independently correlated with lymph node metastasis (PD-L1CPS : OR = -2.5, 95% CI = -4.11 to -0.97, P = 0.008 and PD-L1ICS : OR = -1.85, 95% CI = -2.90 to -0.79, P = 0.004) and < 1.2 CPS and <1.3% ICS were identified as the optimal cut-off values to discriminate between metastatic and non-metastatic patients. In our cohort, the implementation of these cut-off values would have avoided a significant rate of unnecessary surgeries in pN0 patients (PD-L1CPS = 43.2; PD-L1ICS = 51.9%). Ultimately, PD-L1 evaluation showed good interpathologist concordance in absolute terms [PD-L1CPS interclass correlation coefficient (ICC) = 0.91; PD-L1ICS ICC = 0.793] and using the identified cut-off values (PD-L1CPS ICC = 0.848; PD-L1ICS ICC = 0.756). Our study shows that PD-L1 expression is an effective predictor of nodal status and could improve patient selection for surgery after endoscopic removal of pT1 CRCs.

The İmportance of tumor markers in patients undergoing resection for lung metastasis of colorectal carcinoma

In patients with suitable conditions, complete resection is a potential curative treatment for lung metastases of colorectal cancers (CRC). Various prognostic factors affecting survival have been reported in these patients. In our study, the prognostic significance of CEA and CA19-9 tumor markers in patients who underwent lung resection for CRC metastasis was researched. Fifty-three patients who underwent lung resection for CRC metastasis between January 2015 and July 2021 were included in the study. The relationship between preoperative and postoperative CEA and CA19-9 values, survival times, tumor size, and preoperative CEA and CA19-9 levels were investigated. Patients with high preoperative and postoperative CEA had shorter survival (OS) compared with patients with lower values (p≤0.001 and p= 0.009, respectively). Disease-free survival (DFS) was also shorter in patients with higher preoperative CEA values (p= 0.008). For patients with higher preoperative and postoperative CA 19-9 values, OS and DFS were shorter (p= 0.013 and p≤0.001) and (p= 0.042 and p≤0.001), respectively. There was a weak positive correlation between preoperative CEA value and tumor size (p= 0.008, Pearson correlation coefficient =0.360). However, a strong positive correlation between preoperative CA19-9 value and tumor size was discovered (p≤0.001, Pearson correlation coefficient =0.603). In our study, it was shown that preoperative-postoperative CEA and CA19-9 levels in patients with metastatic colon carcinoma are associated with overall survival.

The prognostic role of tumor budding and tumor-stroma ratio in pulmonary metastasis of colorectal carcinoma

ObjectiveTo evaluate the prognostic value of tumor budding and tumor-stroma ratio (TSR) in resected pulmonary metastases of colorectal carcinoma (CRC). MethodsIn total, 106 pulmonary metastasectomies were performed to 74 patients in two study hospitals during 2000–2020. All relevant clinical data were retrospectively collected. Tumor budding based on the International Tumor Budding Consensus Conference recommendations and TSR in the first resected pulmonary metastases and primary tumors were evaluated from diagnostic hematoxylin-eosin-stained histopathological slides. Results60 patients (85.7%) had low tumor budding (≤5 buds/field) and 10 patients (14.3%) had high tumor budding (>5 buds/field) in their first pulmonary metastases of CRC. 5-year overall survival rates of pulmonary metastasectomy in low and high total tumor budding were 28.3% and 37.3% (p = 0.387), respectively. 19 patients (27.1%) had low TSR and 51 patients (72.9%) had high TSR. The 5-year overall survival rates were 32.9% in low and 28.6% in high TSR of first pulmonary metastases (p = 0.746). Tumor budding and TSR did not provide prognostic value in Cox multivariate analysis. Tumor budding and TSR in resected pulmonary metastases were not associated with those of the primary tumor. ConclusionTumor budding and TSR in the resected pulmonary metastases of CRC showed no statistically significant prognostic value, however, additional well-powered confirmatory studies are needed.

Panomics reveals patient individuality as the major driver of colorectal cancer progression

BackgroundColorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity.MethodsWe analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results.ResultsAlthough panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes.ConclusionOur research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.

Correlation of High Eosinophil Count Levels in Blood with Metastasis in Colorectal Carcinoma

Background: Eosinophils are bone marrow-derived granulocytes in peripheral blood and tissues primarily involved as effector cells in colorectal cancer metastasis. High levels of eosinophils correlate with poor prognosis in colorectal cancer. Aim: To prove the correlation between increased levels of eosinophils with clinical stage according to the TNM system and metastatic status in patients with colorectal carcinoma. Methods: An analytical cross-sectional study was conducted from July 2020 to June 2021 at Prof. Dr. IGNG Ngoerah Hospital. Data analysis in this study consisted of univariate analysis, bivariate analysis, and multivariate analysis using SPSS IBM version 23. Results: Obtained 40 subjects patient colorectal cancer where men were 25 (62.5%), mean age ± SD53.15 ± 12.5 years, normal nutritional status 29 (72.5%), most locations in the rectum 16 (40%), followed by descending colon 15 (37.5%), the most clinical-stage IVA 13 (32.5%), lung metastases 12 (30%) with adenocarcinoma type 34 (90%). The average level of eosinophils±SDobtained445.63±283.03. The correlation between eosinophil levels and the clinical stage is strongly positive (r = 0.604; p &lt; 0.001), and with the incidence of distant metastases, a strong positive correlation (r = 0.651; p&lt;0.001). Conclusion: There is a statistically significant correlation between increased levels of eosinophils in the blood in metastases and stages colorectal cancer patients, where the higher the eosinophil count levels, the higher the stage and an increase in the incidence of metastases.