scholarly journals Tissue mRNA for S100A4, S100A6, S100A8, S100A9, S100A11 and S100P Proteins in Colorectal Neoplasia: A Pilot Study

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 402
Author(s):  
Eva Peterova ◽  
Jan Bures ◽  
Paula Moravkova ◽  
Darina Kohoutova

S100 proteins are involved in the pathogenesis of sporadic colorectal carcinoma through different mechanisms. The aim of our study was to assess tissue mRNA encoding S100 proteins in patients with non-advanced and advanced colorectal adenoma. Mucosal biopsies were taken from the caecum, transverse colon and rectum during diagnostic and/or therapeutic colonoscopy. Another biopsy was obtained from adenomatous tissue in the advanced adenoma group. The tissue mRNA for each S100 protein (S100A4, S100A6, S100A8, S100A9, S100A11 and S100P) was investigated. Eighteen biopsies were obtained from the healthy mucosa in controls and the non-advanced adenoma group (six individuals in each group) and thirty biopsies in the advanced adenoma group (ten patients). Nine biopsies were obtained from advanced adenoma tissue (9/10 patients). Significant differences in mRNA investigated in the healthy mucosa were identified between (1) controls and the advanced adenoma group for S100A6 (p = 0.012), (2) controls and the non-advanced adenoma group for S100A8 (p = 0.033) and (3) controls and the advanced adenoma group for S100A11 (p = 0.005). In the advanced adenoma group, differences between the healthy mucosa and adenomatous tissue were found in S100A6 (p = 0.002), S100A8 (p = 0.002), S100A9 (p = 0.021) and S100A11 (p = 0.029). Abnormal mRNA expression for different S100 proteins was identified in the pathological adenomatous tissue as well as in the morphologically normal large intestinal mucosa.

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1066
Author(s):  
Daniel Rodríguez-Alcalde ◽  
Guillermo Castillo-López ◽  
Jorge López-Vicente ◽  
Luis Hernández ◽  
Mercedes Lumbreras-Cabrera ◽  
...  

Serrated polyposis syndrome (SPS) implies a slightly elevated risk of colorectal cancer (CRC) during endoscopic follow-up, but its natural course is still not well known. The main objective of this study was to describe the long-term risk of developing advanced neoplasia (AN) in these patients. Until October 2020, individuals who fulfilled 2010 WHO criteria I and/or III for SPS were retrospectively recruited. We selected those under endoscopic surveillance after resection of all lesions >3 mm in a high-quality colonoscopy. We excluded patients with total colectomy at diagnosis and those with any interval between colonoscopies >3.5 years. We defined AN as advanced serrated polyp (≥10 mm and/or with dysplasia), advanced adenoma, or CRC. In 109 patients, 342 colonoscopies were performed (median = 3, median interval = 1.8 years) during a median follow-up after colonic clearance of 5.0 years. Five-year cumulative incidences of AN were 21.6% globally, and 5.6%, 10.8%, and 50.8% in patients who fulfilled criterion I, III, and both, respectively (p < 0.001). No CRC was diagnosed and only 1 (0.9%) patient underwent surgery. In conclusion, cumulative incidences of AN could be lower than previously described, at least in patients who fulfil the 2010 WHO criterion III alone. Therefore, low-risk individuals might benefit from less stringent surveillance.


2021 ◽  
Vol 11 ◽  
Author(s):  
Li-Chun Chang ◽  
Yi-Chiung Hsu ◽  
Han-Mo Chiu ◽  
Koji Ueda ◽  
Ming-Shiang Wu ◽  
...  

BackgroundPatient participation in colorectal cancer (CRC) screening via a stool test and colonoscopy is suboptimal, but participation can be improved by the development of a blood test. However, the suboptimal detection abilities of blood tests for advanced neoplasia, including advanced adenoma (AA) and CRC, limit their application. We aimed to investigate the proteomic landscape of small extracellular vesicles (sEVs) from the serum of patients with colorectal neoplasia and identify specific sEV proteins that could serve as biomarkers for early diagnosis.Materials and MethodsWe enrolled 100 patients including 13 healthy subjects, 12 non-AAs, 13 AAs, and 16 stage-I, 15 stage-II, 16 stage-III, and 15 stage-IV CRCs. These patients were classified as normal control, early neoplasia, and advanced neoplasia. The sEV proteome was explored by liquid chromatography-tandem mass spectrometry. Generalized association plots were used to integrate the clustering methods, visualize the data matrix, and analyze the relationship. The specific sEV biomarkers were identified by a decision tree via Orange3 software. Functional enrichment analysis was conducted by using the Ingenuity Pathway Analysis platform.ResultsThe sEV protein matrix was identified from the serum of 100 patients and contained 3353 proteins, of which 1921 proteins from 98 patients were finally analyzed. Compared with the normal control, subjects with early and advanced neoplasia exhibited a distinct proteomic distribution in the data matrix plot. Six sEV proteins were identified, namely, GCLM, KEL, APOF, CFB, PDE5A, and ATIC, which properly distinguished normal control, early neoplasia, and advanced neoplasia patients from each other. Functional enrichment analysis revealed that APOF+ and CFB+ sEV associated with clathrin-mediated endocytosis signaling and the complement system, which have critical implications for CRC carcinogenesis.ConclusionPatients with colorectal neoplasia had a distinct sEV proteome expression pattern in serum compared with those patients who were healthy and did not have neoplasms. Moreover, the six identified specific sEV proteins had the potential to discriminate colorectal neoplasia between early-stage and advanced neoplasia. Collectively, our study provided a six-sEV protein biomarker panel for CRC diagnosis at early or advanced stages. Furthermore, the implication of the sEV proteome in CRC carcinogenesis via specific signaling pathways was explored.


2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Juan Lasa ◽  
Astrid Rausch ◽  
Luis Florez Bracho ◽  
Josefina Altamirano ◽  
Daniela Speisky ◽  
...  

Background. The association between celiac disease and colorectal neoplasia has been previously studied, but the question whether recently diagnosed celiac patients show an increased colorectal adenoma prevalence remains unanswered. Aims. To compare the prevalence of colorectal adenomas between adult patients with a recent diagnosis of celiac disease versus healthy controls. Materials and Methods. A retrospective case-control study was undertaken. Patients with a diagnosis of celiac disease at an age of 45 years or more who undertook colonoscopy six months before or six months after the initiation of a gluten-free diet were enrolled as cases. Asymptomatic subjects undertaking screening colonoscopy were recruited as controls in a 2 : 1 fashion. The prevalence of colorectal adenomas and the prevalence of advanced adenomas were compared between groups. Results. 57 celiac disease patients and 118 controls were enrolled. There was a greater prevalence of female patients among the celiac group, with no significant differences in terms of age. There were more obese patients among controls and a higher proportion of tabaquism among celiac patients. Adenoma prevalence was significantly higher among celiac patients (47.37% versus 27.97%, p=0.01). Advanced adenoma detection was not different between groups. Conclusion. Adult patients with a recent diagnosis of celiac disease have an increased prevalence of colorectal adenomas.


2016 ◽  
Vol 84 (6) ◽  
pp. 971-982.e6 ◽  
Author(s):  
Ryota Niikura ◽  
Hideo Yasunaga ◽  
Atsuo Yamada ◽  
Hiroki Matsui ◽  
Kiyohide Fushimi ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Paula Moravkova ◽  
Darina Kohoutova ◽  
Stanislav Rejchrt ◽  
Jiri Cyrany ◽  
Jan Bures

The family of S100 proteins represents 25 relatively small (9–13 kD) calcium binding proteins. These proteins possess a broad spectrum of important intracellular and extracellular functions. Colorectal cancer is the third most common cancer in men (after lung and prostate cancer) and the second most frequent cancer in women (after breast cancer) worldwide. S100 proteins are involved in the colorectal carcinogenesis through different mechanisms: they enable proliferation, invasion, and migration of the tumour cells; furthermore, S100 proteins increase angiogenesis and activate NF-κβsignaling pathway, which plays a key role in the molecular pathogenesis especially of colitis-associated carcinoma. The expression of S100 proteins in the cancerous tissue and serum levels of S100 proteins might be used as a precise diagnostic and prognostic marker in patients with suspected or already diagnosed colorectal neoplasia. Possibly, in the future, S100 proteins will be a therapeutic target for tailored anticancer therapy.


2016 ◽  
Vol 63 (2) ◽  
pp. 115-117
Author(s):  
Beatrice Lintoiu ◽  
◽  
Irina Balescu ◽  
Nicolae Bacalbasa ◽  
◽  
...  

Schwannomas are rare tumors originating from the Schwann cells, that form the neural sheath. These tumors occur most frequently in the head, neck, arms and limbs. Primary schwannomas of the colon and rectum are extremely rare. They are usually benign. Pre-operative biopsy examinations may be difficult and immunohistochemistry is necessary for the correct diagnosis. In contrast to gastrointestinal stromal tumors, schwannomas are negative for CD117 and positive for S100 protein and vimentin. In extremely rare cases, they can present with malignant degeneration if not surgically removed. Therefore, the gold standard treatment for schwannomas is surgical resection.


Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_4) ◽  
Author(s):  
Sean Joseph Donohue ◽  
Angela Midgley ◽  
Ian Bruce ◽  
Michael W Beresford ◽  
Christian M Hedrich

Abstract Background Juvenile-onset SLE (JSLE) is a systemic autoimmune disease affecting young people before the age of 17 years. Despite recent progress in understanding the pathogenesis of JSLE, it remains unclear. The lack of reliable biomarkers makes the assessment of disease activity and organ involvement challenging. A family of pro-inflammatory molecules known as S100 proteins have recently emerged as potential biomarkers for monitoring disease activity in an adult-onset SLE and various (auto-) inflammatory conditions. We investigated the usefulness of S100A8/A9 and S100A12 serum and urine levels as biomarkers for renal involvement and/or disease activity in JSLE. Methods Serum and urine from JSLE patients (n = 60), matched healthy controls (n = 53) and patients with IgA vasculitis (disease controls, n = 9) were collected. S100A8/A9 and S100A12 concentrations in serum and urine samples were quantified using the Meso Scale Discovery Immunoassay [serum; median ng/mL (I.Q.R), urine; median ng/mmol creatinine (I.Q.R)]. Furthermore, S100 protein concentrations in serum and urine were compared between groups and between JSLE patients with active (BILAG scores A, B, C) and inactive (BILAG scores D, E) renal disease. Potential effects of age, sex and global disease activity (SLEDAI scores) on S100 protein concentrations were tested. Results S100A8/A9 levels were significantly increased in the serum of JSLE patients [1577.80ng/mL (2313.97)] when compared to healthy controls [732.53 ng/mL (1003.47); p < 0.001)] and patients with IgA vasculitis [531.23 ng/mL (824.50); p < 0.05)]. This, however, was not reflected in patients’ urine samples. S100A12 concentrations were significantly increased in both the serum [41.12 ng/mL = (106.06); p < 0.05] and urine [90.12ng/mmol creatinine (348.44); p < 0.05] when compared to healthy controls [serum;17.75ng/mL(47.16), urine; 14.88ng/mmol creatinine (198.36)]. No differences were seen between S100A12 protein levels in serum or urine of JSLE patients when compared to patients with IgA vasculitis. No differences were observed between S100 protein concentrations in the serum or urine of patients with JSLE with active vs. inactive renal disease, between ages or sexes. Also, global disease activity (SLEDAI) did not correlate with serum or urine S100 protein concentrations. Conclusion JSLE patients exhibit increased concentrations of S100A8/A9 and S100A12 proteins in the serum, independent of clinical disease activity. Furthermore, increased urine concentrations of S100A12 in JSLE patients are independent of current renal involvement or activity. Based on the small molecular weight of S100 proteins, this may suggest renal loss of elevated serum S100A12 (21 kDa) through the kidneys rather than being the result of kidney inflammation or damage. Thus, S100 proteins may help to distinguish JSLE patients from healthy controls and patients with the differential diagnosis IgA vasculitis, supporting previous reports in adult-onset SLE. Longitudinal assessment of S100 proteins for an individual patient and/or in combination with other biomarkers may be helpful in assessing disease activity in JSLE patients. Conflicts of Interest The authors declare no conflicts of interest.


2004 ◽  
Vol 20 (4-5) ◽  
pp. 283-288 ◽  
Author(s):  
M. H. Sun

Extent neuroendocrine differentiation can be encountered in many human neoplasm derived from different organs and systems using immunohistochemistry and ultrastructural techniques. The tumor cells' behaviors resemble those of neurons and neuroendocrine cells. The presence of neuroendocrine differentiation reputedly appears to be associated with a poorer prognosis than the adenocarcinoma counterparts in sporadic human neoplasm. In this review the neuroendocrine carcinoma and the adenocarcinoma with neuroendocrine differentiation of colon and rectum both in sporadic colorectal carcinoma and the hereditary nonpolyposis colorectal cancer, the relationship of neuroendocrine differentiation and some possible molecular pathways in tumorogenesis of colorectal cancer will be discussed. Possible treatment strategy will also be addressed.


Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1542 ◽  
Author(s):  
María Marcuello ◽  
Saray Duran-Sanchon ◽  
Lorena Moreno ◽  
Juan José Lozano ◽  
Luis Bujanda ◽  
...  

Early detection of colorectal cancer (CRC) and its precancerous lesion, advanced adenomas (AA), is critical to improve CRC incidence and prognosis. Circulating microRNAs (miRNAs or miR) are promising non-invasive biomarkers for cancer detection. Our previous results showed that a plasma 6-miRNA signature (miR-15b-5p, miR-18a-5p, miR-29a-3p, miR-335-5p, miR-19a-3p and miR-19b-3p) could distinguish between CRC or AA and healthy individuals (controls). However, its diagnostic performance in serum is unknown. In this exploratory study we aim to evaluate the diagnostic performance of the 6-miRNA signature in serum samples in a cohort of individuals participating in Barcelona’s CRC Screening Programme. We prospectively collected serums from 264 faecal immunochemical test (FIT)-positive participants and total RNA was extracted. Finally, 213 individuals (CRC, 59, AA, 74, controls, 80) were included. MiRNA expression was quantified by real-time RT-qPCR and data analysis was performed by logistic regression. Faecal hemoglobin concentration (f(Hb)) from FIT of the same individuals was also considered. As previously described in plasma, serum from patients with AA or CRC presented significant differences in the 6-miRNA signature compared to controls. Moreover, when combined with f(Hb), the final signature showed high discriminative capacity to distinguish CRC from controls (area under the curve (AUC) = 0.88), and even AA (AUC = 0.81) that otherwise are poorly detected if we only consider f(Hb) (AUC = 0.64). Addition of the serum 6-miRNA signature to quantitative f(Hb) show high accuracy to detect patients with advanced colorectal neoplasia in average-risk individuals. A combination of these two non-invasive methods could be a good strategy to improve diagnostic performances of current CRC screening programmes.


Gut ◽  
2019 ◽  
Vol 69 (2) ◽  
pp. 304-310 ◽  
Author(s):  
Siew C Ng ◽  
Moe Htet Kyaw ◽  
Bing Yee Suen ◽  
Yee Kit Tse ◽  
Martin C S Wong ◽  
...  

ObjectiveThe risk associated with a family history of non-advanced adenoma (non-AA) is unknown. We determined the prevalence of colorectal neoplasms in subjects who have a first-degree relative (FDR) with non-AA compared with subjects who do not have an FDR with adenomas.DesignIn a blinded, cross-sectional study, consecutive subjects with newly diagnosed non-AA were identified from our colonoscopy database. 414 FDRs of subjects with non-AA (known as exposed FDRs; mean age 55.0±8.1 years) and 414 age and sex-matched FDRs of subjects with normal findings from colonoscopy (known as unexposed FDRs; mean age 55.2±7.8 years) underwent a colonoscopy from November 2015 to June 2018. One FDR per family was recruited. FDRs with a family history of colorectal cancer were excluded. The primary outcome was prevalence of advanced adenoma (AA). Secondary outcomes included prevalence of all adenomas and cancer.ResultsThe prevalence of AA was 3.9% in exposed FDRs and 2.4% in unexposed FDRs (matched OR (mOR)=1.67; 95% CI 0.72 to 3.91; p=0.238 adjusted for proband sex and proband age). Exposed FDRs had a higher prevalence of any adenomas (29.2% vs 18.6%; mOR=1.87; 95% CI 1.32 to 2.66; p<0.001) and non-AA (25.4% vs 16.2%; mOR=1.91; 95% CI 1.32 to 2.76; p=0.001). A higher proportion of exposed FDRs than unexposed FDRs (4.3% vs 2.2%; adjusted mOR=2.44; 95% CI 1.01 to 5.86; p=0.047) had multiple adenomas. No cancer was detected in both groups.ConclusionA positive family history of non-AA does not significantly increase the risk of clinically important colorectal neoplasia. The data support current guidelines which do not advocate earlier screening in individuals with a family history of non-AA.Trial registration numberNCT0252172.


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