Rectal and colon cancer: Not just a different anatomic site

Tamás, K.; Walenkamp, Annemiek; Vries, de Elisabeth G. E.; Vugt, van Marcel; Beets‐Tan, Regina G. H.; Etten, Boudewijn van; Groot, Derk Jan A. de; Hospers, Geke A.P.

doi:10.1016/j.ctrv.2015.06.007

Cited by 258 publications

(205 citation statements)

References 110 publications

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“…Although CRC patient mortality rates are decreasing because of improved screening and treatment methods, CRC remains the third most commonly diagnosed cancer in the United States [1] and the third most important cause of cancer-related death globally [2]. Colonic and rectal cancers are often combined as a single entity in many studies but they differ in their metastatic pattern, drug response, and optimal treatment methods [3]. Rectal cancer patients experience poorer survival outcomes than colon cancer patients because resection is more difficult [4]; therefore, selection of appropriate treatment is especially important for rectal cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis

Chung

Singh

et al. 2018

BMC Cancer

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BackgroundThe MRE11/RAD50/NBS1 (MRN) complex plays an essential role in detecting and repairing double-stranded breaks, and thus the potential roles of MRE11, RAD50 and NBS1 proteins in the pathogenesis of various cancers is the subject of investigation. This study was aimed at assessing the three-protein panel of MRN complex subunits as a potential radiosensitivity marker and evaluating the prognostic and clinicopathological implications of MRN expression in rectal cancer.MethodsSamples from 265 rectal cancer patients treated with surgery and adjuvant chemoradiotherapy, including samples from 55 patients who were treated with neoadjuvant radiotherapy between 2000 and 2011, were analyzed. Expression of MRN complex proteins in tissue samples was determined by immunohistochemistry. Univariate and multivariate analyses were carried out to identify clinicopathological characteristics that are associated with the MRN three-protein panel expression in rectal cancer samples.ResultsIn Kaplan–Meier survival analyses, we found that high level expression of MRN complex proteins in postoperative samples was associated with poor disease-free (p = 0.021) and overall (P = 0.002) survival. Interestingly, high MRN expression also correlated with poor disease-free (P = 0.047) and overall (P = 0.024) survival in the neoadjuvant radiotherapy subgroup. In multivariate analysis, combined MRN expression (hazard ratio = 2.114, 95% confidence interval 1.096–4.078, P = 0.026) and perineural invasion (hazard ratio = 2.160, 95% confidence interval 1.209–3.859, P = 0.009) were significantly associated with a worse disease-free survival.ConclusionsExpression levels of MRN complex proteins significantly predict disease-free survival in rectal cancer patients, including those treated with neoadjuvant radiotherapy, and may have value in the management of these patients.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4776-9) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

“…Neoadjuvant (i.e., preoperative) radiotherapy or chemoradiation is routinely used to treat patients with rectal cancer to improve surgical outcomes [3]. Many studies have found that this therapy improves overall survival (OS) and reduce recurrence [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis

Chung

Singh

et al. 2018

BMC Cancer

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“…Colorectal cancer (CRC) is one of the most malignant cancers diagnosed in the gastrointestinal tract (GIT), which requires different staging criteria, adjuvant treatment and operative methods [1]. Environment and genetic factors have been long-standing issues in the germination and progression of colon cancer [2].…”

Section: Introductionmentioning

confidence: 99%

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin

Chen

Hou

Gao

et al. 2018

Cell Physiol Biochem

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Background/Aims: The present study was aimed at examining Ezrin expression in human colorectal cancer (CRC) tissues and elucidating the influence of baicalein on the proliferation of HCT116 cells. Methods: The expression of Ezrin was determined by qRT-PCR and immunohistochemistry. HCT116 cells were divided into four groups－ baicalein groups with various concentrations, pcDNA3.1-Ezrin group, si-Ezrin group and dual inhibitory group (baicalein + si-Ezrin). CCK-8 assay and flow cytometry (FCM) were employed to assess cell proliferation and to detect the distribution of cell cycle respectively. The expression levels of Ezrin protein and cell cycle-associated proteins were detected by using western blot. The proliferation ability of CRC cells was also evaluated in vivo. Results: Ezrin expression in CRC tissues was observably higher than that in adjacent colorectal tissues. With drug concentration and action time of baicalein increasing, the cell propagation capacity of HCT116 cells was decreased and the cell cycle progression was arrested. Ezrin expression was inhibited by the administration of baicalein in a dose-dependent way. The levels of CyclinD1 and CDK4 were also significantly decreased, but the expression of P53 pathway proteins P53 and P21 was markedly upregulated. Conclusion: Baicalein repressed proliferation of human colorectal cancer cells HCT116 and blocked cell cycle through downregulating Ezrin and upregulating P53 pathway-related proteins.

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“…Whereas, colon and rectal cancers have been routinely studied together as CRC, evidences indicate these to be distinct nosological entities. Differences in embryological origin, anatomy, treatment, metastatic potential, and outcome between colon cancer and rectal cancer have led to discussions as to whether neoplastic lesions of these two anatomical sites should be considered as different diseases, with further dichotomization of colon cancers into distal and proximal (Tamas et al, 2015). …”

Section: Introductionmentioning

confidence: 99%

Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community Profiling

Thomas

Jesus

Lopes

et al. 2016

Front. Cell. Infect. Microbiol.

120

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Sporadic and inflammatory forms of colorectal cancer (CRC) account for more than 80% of cases. Recent publications have shown mechanistic evidence for the involvement of gut bacteria in the development of both CRC-forms. Whereas, colon and rectal cancer have been routinely studied together as CRC, increasing evidence show these to be distinct diseases. Also, the common use of fecal samples to study microbial communities may reflect disease state but possibly not the tumor microenvironment. We performed this study to evaluate differences in bacterial communities found in tissue samples of 18 rectal-cancer subjects when compared to 18 non-cancer controls. Samples were collected during exploratory colonoscopy (non-cancer group) or during surgery for tumor excision (rectal-cancer group). High throughput 16S rRNA amplicon sequencing of the V4–V5 region was conducted on the Ion PGM platform, reads were filtered using Qiime and clustered using UPARSE. We observed significant increases in species richness and diversity in rectal cancer samples, evidenced by the total number of OTUs and the Shannon and Simpson indexes. Enterotyping analysis divided our cohort into two groups, with the majority of rectal cancer samples clustering into one enterotype, characterized by a greater abundance of Bacteroides and Dorea. At the phylum level, rectal-cancer samples had increased abundance of candidate phylum OD1 (also known as Parcubacteria) whilst non-cancer samples had increased abundance of Planctomycetes. At the genera level, rectal-cancer samples had higher abundances of Bacteroides, Phascolarctobacterium, Parabacteroides, Desulfovibrio, and Odoribacter whereas non-cancer samples had higher abundances of Pseudomonas, Escherichia, Acinetobacter, Lactobacillus, and Bacillus. Two Bacteroides fragilis OTUs were more abundant among rectal-cancer patients seen through 16S rRNA amplicon sequencing, whose presence was confirmed by immunohistochemistry and enrichment verified by digital droplet PCR. Our findings point to increased bacterial richness and diversity in rectal cancer, along with several differences in microbial community composition. Our work is the first to present evidence for a possible role of bacteria such as B. fragilis and the phylum Parcubacteria in rectal cancer, emphasizing the need to study tissue-associated bacteria and specific regions of the gastrointestinal tract in order to better understand the possible links between the microbiota and rectal cancer.

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Rectal and colon cancer: Not just a different anatomic site

Cited by 258 publications

References 110 publications

Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis

Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin

Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community Profiling

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