Dataset Information

A nationwide Danish cohort study challenging the categorisation into right-sided and left-sided colon cancer.

ABSTRACT:

Objectives

The categorisation of colon cancer (CC) into right-sided (RCC) and left-sided (LCC) disease may not capture more subtle variances in aetiology and prognosis. In a nationwide study, we investigated differences in clinical characteristics and survival of RCC versus LCC and of the complete range of CC subsites.

Design

Prospective nationwide cohort study.

Setting

The database of the Danish Colorectal Cancer Group (DCCG).

Participants

23 487 CC patients.

Outcome measures

Overall survival (Kaplan-Meier plots) and mortality (HR from Cox proportional hazards regression analysis) according to CC localisation. For adjustment and stratification, we used age, sex, ASA score (the American Society of Anaesthesiologists score), tumour location and stage, number of lymph nodes harvested at operation, number of lymph nodes with metastases and presence of distant metastases.

Results

Patients with RCC had a higher median age at diagnosis (74.3 years) than patients with LCC (71.8 years; p<0.0001). Overall, the proportion of patients who were women increased the closer the tumour site was to the small intestine. Although RCC patients had higher ASA scores than LCC patients (p<0.0001), the highest ASA scores were observed in patients with cancer in the transverse and descending colon and at both colon flexures. While RCCs overall were more advanced than LCCs (p<0.0001), the most advanced CCs were those of the descending colon, splenic flexure and caecum. RCC mortality was higher than LCC mortality only during the first 2 years (women: HR 1.13; 95% CI 1.06 to 1.20; men: HR 1.27; 95% CI 1.20 to 1.35), and relative to mortality from sigmoid CC, the highest mortality was observed from splenic flexure cancer (HR 1.75; 95% CI 1.54 to 2.00).

Conclusions

The present data challenge the simple categorisation of CC into RCC and LCC.

SUBMITTER: Jess P

PROVIDER: S-EPMC3657647 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Publications

A nationwide Danish cohort study challenging the categorisation into right-sided and left-sided colon cancer.

Jess Per P Hansen Iben Onsberg IO Gamborg Michael M Jess Tine T

BMJ open 20130528 5

<h4>Objectives</h4>The categorisation of colon cancer (CC) into right-sided (RCC) and left-sided (LCC) disease may not capture more subtle variances in aetiology and prognosis. In a nationwide study, we investigated differences in clinical characteristics and survival of RCC versus LCC and of the complete range of CC subsites.<h4>Design</h4>Prospective nationwide cohort study.<h4>Setting</h4>The database of the Danish Colorectal Cancer Group (DCCG).<h4>Participants</h4>23 487 CC patients.<h4>Out ...[more]

PMID: 23793665

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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.

Project description:BackgroundLeft-sided and right-sided colon cancers (LCCs and RCCs, respectively) differ in their epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and prognosis. Notably, immune response gene expression profiles have been shown to differ between patients with LCC and patients with RCC. The immune system plays an important role in tumor immunosurveillance, and there is increasing evidence that peripheral blood immune cells have a profound influence on tumor prognosis. This study aimed to determine the clinical significance of circulating immune cells with respect to colon tumor locations.MethodsDifferent types of circulating immune cells were separated and analysed based on their surface markers by flow cytometry. We compared the numbers of dendritic cells (DCs) and T cell subsets in the peripheral blood of 94 patients with RCC or LCC and analysed the proportions of these immune cells in relation to tumor stage, tumor differentiation and lymphatic metastasis.ResultsWe show that at later tumor stages, patients with LCC had higher levels of circulating myeloid DCs (P = 0.049) and plasmacytoid DCs (P = 0.018) than patients with RCC. In poorly differentiated tumors, LCC patients had significantly higher amount of plasmacytoid DCs (P = 0.036), CD4+ memory T (Tm) cells (P = 0.012), CD4+ T cells (P = 0.028), Tm cells (P = 0.014), and regulatory T cells (P = 0.001) than RCC patients. The levels of circulating CD4+ T cells, Tm cells and CD4+ Tm cells were significantly elevated at later stages in patients with LCC or RCC, while these cells decreased in poorly differentiated tumors in patients with RCC. Moreover, CD4+ Tm cell and CD4+ T cell levels are significantly associated with lymph node metastasis in patients with LCC and RCC.DiscussionCirculating immune cells were associated with tumor location, tumor stage and tumor differentiation, and can be used to predict lymphatic metastasis in patients with colon cancer. This variation in systemic immunity could contribute to the differential prognosis of patients with colon cancer.

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.

Dataset Information

A nationwide Danish cohort study challenging the categorisation into right-sided and left-sided colon cancer.

Objectives

Design

Setting

Participants

Outcome measures

Results

Conclusions

Publications

A nationwide Danish cohort study challenging the categorisation into right-sided and left-sided colon cancer.

Similar Datasets

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