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Project description:Epigenetic processes regulating gene expression contribute markedly to epithelial cell plasticity in colorectal carcinogenesis. The lysine methyltransferase SUV420H2 comprises an important regulator of epithelial plasticity and is primarily responsible for trimethylation of H4K20 (H4K20me3). Loss of H4K20me3 has been suggested as a hallmark of human cancer due to its interaction with DNMT1. However, the role of Suv4-20h2 in colorectal cancer is unknown.
2022-11-09 | GSE217265 | GEO
Project description:Epigenetic processes regulating gene expression contribute markedly to epithelial cell plasticity in colorectal carcinogenesis. The lysine methyltransferase SUV420H2 comprises an important regulator of epithelial plasticity and is primarily responsible for trimethylation of H4K20 (H4K20me3). Loss of H4K20me3 has been suggested as a hallmark of human cancer due to its interaction with DNMT1. However, the role of Suv4-20h2 in colorectal cancer is unknown.
2022-11-09 | GSE217266 | GEO
Project description:Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups respond differently to biological therapies. Historically, management of patients with metastatic colon and rectal cancers has been similar, and colon and rectal cancer patients have been grouped together in large clinical trials. Clearly, the differences in molecular biology among right-sided colon, left-sided colon, and rectal cancers should be further studied in order to account for disparities in clinical outcomes. We profiled 10,570 colorectal tumors (of which 2,413 were identified as arising from the left colon, right colon, or rectum) using next-generation sequencing, immunohistochemistry, chromogenic in-situ hybridization, and fragment analysis (Caris Life Sciences, Phoenix, AZ). Right-sided colon cancers had higher rates of microsatellite instability, more frequent aberrant activation of the EGFR pathway including higher BRAF and PIK3CA mutation rates, and increased mutational burden compared to left-sided colon and rectal cancers. Rectal cancers had higher rates of TOPO1 expression and Her2/neu amplification compared to both left- and right-sided colon cancers. Molecular variations among right-sided colon, left-sided colon, and rectal tumors may contribute to differences in clinical behavior. The site of tumor origin (left colon, right colon, or rectum) should certainly be considered when selecting treatment regimens and stratifying patients for future clinical trials.
| S-EPMC5689690 | biostudies-other
Project description:BackgroundGiven the differences in embryonic origin, vascular and nervous supplies, microbiotic burden, and main physiological functions of left and right colons, tumor location is increasingly suggested to dictate tumor behavior affecting pathology, progression and prognosis. Right-sided colon cancers arise in the cecum, ascending colon, hepatic flexure and/or transverse colon, while left-sided colon cancers arise in the splenic flexure, descending, and/or sigmoid colon. In contrast to prior reports, we attempt to delineate programs of tumorigenesis independently for each side.MethodsFour hundred and eleven samples were extracted from The Cancer Genome Atlas-COAD cohort, based on a conservative sample inclusion criterion. Each side was independently analyzed with respect to their respective normal tissue, at the level of transcription, post-transcription, miRNA control and methylation in both a stage specific and stage-agnostic manner.ResultsOur results indicate a suppression of enzymes involved in various stages of carcinogen breakdown including CYP2C8, CYP4F12, GSTA1, and UGT1A within right colon tumors. This implies its reduced capacity to detoxify carcinogens, contributing to a genotoxic tumor environment, and subsequently a more aggressive phenotype. Additionally, we highlight a crucial nexus between calcium homeostasis (sensing, mobilization and absorption) and immune/GPCR signaling within left-sided tumors, possibly contributing to its reduced proliferative and metastatic potential. Interestingly, two genes SLC6A4 and HOXB13 show opposing regulatory trends within right and left tumors. Post-transcriptional regulation mediated by both RNA-binding proteins (e.g. NKRF (in left) and MSI2 (in right)) and miRNAs (e.g. miR-29a (in left); miR-155, miR181-d, miR-576 and miR23a (in right)) appear to exhibit side-specificity in control of their target transcripts and is pronounced in right colon tumors. Additionally, methylation results depict location-specific differences, with increased hypomethylation in open seas within left tumors, and increased hypermethylation of CpG islands within right tumors.ConclusionsDifferences in molecular mechanisms captured here highlight distinctions in tumorigenesis and progression between left and right colon tumors, which will serve as the basis for future studies, influencing the efficacies of existing and future diagnostic, prognostic and therapeutic interventions.
| S-EPMC7161305 | biostudies-literature
Project description:The difference between left- and right-sided colon cancer has become the focus of global attention, and researchers have found differences in the morbidity, molecular biological characteristics, and response to targeted drug therapy between left- and right-sided colon cancer. Therefore, the identification of more effective predictive indicators is critical for providing guidance to future clinical work. We collected samples from different colon sites and regions and analyzed the identities and distributions of differentially expressed species in the microbiota in the left and right sides of the colon to better explore the pathogenesis of colon cancer and provided a basis for individualized drug therapy. We collected samples from different regions in the body of 40 patients with colon cancer, including stool and tissues. The Subjects were classified into four groups, and this classification was mainly based on the colon cancer distribution. The microbiota composition of the left-sided and right-sided colon samples was assessed by specifically amplifying the V3-V4 region of the 16S rDNA gene from DNA extracts from the samples. These amplicons were examined by Illumina HiSeq 2500 sequencing. The microbial taxa in the left-sided colon samples are more abundant than those in the right-sided colon samples. The flora in the left-sided colon samples, such as Clostridium perfringens and Fusobacterium nucleatum, might be associated with VEGF expression and are more likely to promote colon cancer. The microbiota distribution in the right-sided colon samples is less invasive and harmful and particularly rich in Bifidobacterium dentium. In addition, Streptococcus, which is the target of EGFR, was found to be expressed in both the left- and right-sided colon samples but was found at a higher level in the left-sided colon samples. Additionally, the differential pathways involved in the left-sided colon samples mainly mediate DNA damage, methylation, and histone modifications, whereas those in the right-sided colon samples are dominated by DNA synthesis. The comparison of only the geographical differences revealed a significant difference in the distribution of the microbial population. The adherent microbiota composition and structural changes between the left- and right-sided colon samples might contribute to the development of colon cancer, lead to different morbidities, and further affect the prognosis of patients and their sensitivity to targeted drugs. Therefore, the identification of the differential flora in the colon could be used as an indicator for predicting the occurrence and development of colon cancer, which is also beneficial for future individualized drug therapy.
| S-EPMC7726112 | biostudies-literature
Project description:This study aimed to explore the association of tumor sidedness with the prognosis of patients with colon signet ring cell carcinoma (SRCC). Eligible patients were retrieved from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Cancer-specific survival (CSS) and overall survival (OS) were compared between patients with left-sided colon SRCC and those with right-sided lesions. A total of 2660 patients were included, among them, 1983 (74.5%) had right-sided colon SRCC. Compared to patients with left-sided colon SRCC, those who had the right-sided colon SRCC showed higher proportion of white race, female, aged ??65 years, receiving total colectomy and ??4 regional lymph node dissection; while had lower proportion of advanced AJCC stage. Besides, right-sided patients exhibited superior 5-year CSS (32.74% vs. 25.89%, P?=?0.001) and OS (27.38% vs. 23.02%, P?=?0.024) rates compared with left-sided ones. Multivariate analysis revealed that tumor sidedness was an independent prognostic factor. To be specific, patients with right-sided colon SRCC showed better CSS (HR: 0.873; 95% CI 0.777-0.981; P?=?0.023) and OS (HR: 0.838; 95% CI 0.753-0.965; P?=?0.002). Moreover, subgroup analysis demonstrated superior CSS and OS for right-sided patients in most subgroups. Tumor sidedness was an independent prognostic indicator for colon SRCC. Besides, patients with right-sided colon SRCC have superior prognosis than those with left-sided lesions.
| S-EPMC7578060 | biostudies-literature
Project description:The colon is derived from the embryological midgut and hindgut separately, with the right colon and left colon having different features with regards to both anatomical and physiological characteristics. Cancers located in the right and left colon are referred to as right colon cancer (RCC) and left colon cancer (LCC), respectively, based on their apparent anatomical positions. Increasing evidence supports the notion that not only are there differences in treatment strategies when dealing with RCC and LCC, but molecular features also vary between them, not to mention the distinguishing clinical manifestations. Disease-free survival after radical surgery of both RCC and LCC are similar. In the treatment of RCC, the benefit gained from adjuvant FOLFIRI chemotherapy is superior, or at least similar, to LCC, but inferior to LCC if FOLFOX regimen is applied. On the other hand, metastatic LCC exhibits longer survival than that of RCC in a palliative chemotherapy setting. For KRAS wild-type cancers, LCC benefits more from cetuximab treatment than RCC. Moreover, advanced LCC shows a higher sensitivity to bevacizumab treatment in comparison with advanced RCC. Significant varieties exist at the molecular level between RCC and LCC, which may serve as the cause of all apparent differences. With respect to carcinogenesis mechanisms, RCC is associated with known gene types, such as MMR, KRAS, BRAF, and miRNA-31, while LCC is associated with CIN, p53, NRAS, miRNA-146a, miRNA-147b, and miRNA-1288. Regarding protein expression, RCC is related to GNAS, NQO1, telomerase activity, P-PDH, and annexin A10, while LCC is related to Topo I, TS, and EGFR. In addition, separated pathways dominate progression to relapse in RCC and LCC. Therefore, RCC and LCC should be regarded as two heterogeneous entities, with this heterogeneity being used to stratify patients in order for them to have the optimal, current, and novel therapeutic strategies in clinical practice. Additional research is needed to uncover further differences between RCC and LCC.
| S-EPMC4458758 | biostudies-literature
Project description:Mountain of studies has showed that right-sided colon cancer (RSCC) and left-sided colon cancer (LSCC) have different clinical presentation and biologic features and should be considered as two distinct disease entities. The survival difference between RSCC and LSCC remains controversial. Using Surveillance, Epidemiology, and End Results (SEER) database, we identified colon adenocarcinoma patients from 2004 to 2013. The 5-year cause-specific survival (CSS) was our primary endpoint. All statistical analyses were performed using the Intercooled Stata 13.0. All statistical tests were two-sided. The study included 95,847 (58.72%) RSCC and 67,385 (41.28%) LSCC patients. RSCC patients were older, more often females, more Caucasian, more unmarried, more advanced T and N stage, larger tumor sizes, and more poorly differentiated tumor, while LSCC patients had more stage IV diseases. Location was an independent prognostic factor in the multivariable analysis. Compared with RSCC patients, the hazard ratio for LSCC was 0.87, 95% CI: 0.85-0.89 P < 0.001. There was no survival difference between RSCC and LSCC in the following situations: older than 68 years old, T3-4, N0, poorly differentiated, and undifferentiated diseases. We firstly reported that RSCC patients had a better prognosis than LSCC in mucinous adenocarcinoma/signet ring cell carcinoma patients. RSCC patients also had a better prognosis than LSCC in stage II disease. There is a need for further subdivisions when analyzing the survival difference between RSCC and LSCC patients. RSCC had lower mortality rate than LSCC in stage II disease and mucinous adenocarcinoma/signet ring cell carcinoma patients.
| S-EPMC5911618 | biostudies-literature
Project description:BackgroundEn bloc right hemicolectomy with pancreatoduodenectomy (RHCPD) is the optimum treatment to achieve the adequate margin of resection (R0) for locally advanced right-sided colon cancer with duodenal invasion. Information regarding the indications and outcomes of this procedure is limited.MethodIn this retrospective study, 2269 patients with right colon cancer underwent radical right colectomy between October 2010 and May 2019, in which 19 patients underwent RHCPD for LARCC were identified. The overall survival (OS), disease-free survival (DFS), operative mortality, postsurgical complications, gene mutational analysis, and prognostic factors were evaluated. Survival was estimated using Kaplan-Meir method.ResultsOf these 19 patients who underwent LARCC, the OS was 88%, 66%, and 58% at 1, 3, and 5 years. The DFS was 72%, 56%, and 56% at 1, 3, and 5 years. The median operative time was 320 min (range: 222-410 min), and the median operative blood loss was 268 mL (range: 100-600 mL). The OS was significantly better among patients with well-differentiated tumor, N0 stage, and high microsatellite instability (MSI) and in patients who received adjuvant chemotherapy. The major postoperative complications occurred in 8 patients (42%), with pancreatic fistula (PF) being the most common. On the basis of the univariate analysis, poorly differentiated tumor, regional lymph node dissemination, MSI status, and no perioperative chemotherapy were the significant predictors of poor survival (P < 0.05).ConclusionsThis study suggests that RHCPD is feasible and can achieve complete tumor clearance with favorable outcome, particularly in patients with lymph node-negative status.
| S-EPMC8243482 | biostudies-literature
Project description:Right-sided colon cancer (RCC) has worse prognosis compared to left-sided colon cancer (LCC) and rectal cancer. The reason for this difference in outcomes is not well understood. We performed comparative somatic and proteomic analyses of RCC, LCC and rectal cancers to understand the unique molecular features of each tumor sub-types. Utilizing a novel in silico clonal evolution algorithm, we identified common tumor-initiating events involving APC, KRAS and TP53 genes in RCC, LCC and rectal cancers. However, the individual role-played by each event, their order in tumor development and selection of downstream somatic alterations were distinct in all three anatomical locations. Some similarities were noted between LCC and rectal cancer. Hotspot mutation analysis identified a nonsense mutation, APC R1450* specific to RCC. In addition, we discovered new significantly mutated genes at each tumor location, Further in silico proteomic analysis, developed by our group, found distinct central or hub proteins with unique interactomes among each location. Our study revealed significant differences between RCC, LCC and rectal cancers not only at somatic but also at proteomic level that may have therapeutic relevance in these highly complex and heterogeneous tumors.
| S-EPMC6303985 | biostudies-literature