scholarly journals The Rectal Cancer microRNAome – microRNA Expression in Rectal Cancer and Matched Normal Mucosa

2012 ◽  
Vol 18 (18) ◽  
pp. 4919-4930 ◽  
Author(s):  
Jochen Gaedcke ◽  
Marian Grade ◽  
Jordi Camps ◽  
Rolf Søkilde ◽  
Bogumil Kaczkowski ◽  
...  
2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuntao Shi ◽  
Yingying Zhuang ◽  
Jialing Zhang ◽  
Mengxue Chen ◽  
Shangnong Wu

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Zeljko Martinovic ◽  
Drazen Kovac ◽  
Mia Martinovic

Background. The role of endoglin in the Dukes B rectal cancer is still unexplored. The aim of this study was to examine the expression of endoglin (CD105) in resected rectal cancer and to evaluate the relationship between microvessels density (MVD), clinicopathological factors, and survival rates.Methods. The study included 95 primary rectal adenocarcinomas, corresponding to 67 adjacent and 73 distant normal mucosa specimens from surgical resection samples. Tumor specimens were paraffin-embedded and immunohistochemical staining for the CD105 endothelial antigen was performed to count CD105-MVD. For exact measurement of the CD105-MVD used a computer-integrated system Alphelys Spot Browser 2 was used.Results. The intratumoral CD105-MVD was significantly higher compared with corresponding adjacent mucosa (P<0.0001) and distant mucosa specimens (P<0.0001). There was no significant difference in the CD105-MVD according to patients age, gender, tumor location, grade of differentiation, histological type, depth of tumor invasion, and tumor size. The overall survival rate was significantly higher in the low CD105-MVD group of patients than in the high CD105-MVD group of patients (log-rank test,P=0.0406).Conclusion. CD105-assessed MVD could help to identify patients with possibility of poor survival in the group of stage II RC.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15102-e15102
Author(s):  
Chao-Jie Wang ◽  
Jian-Wei Zhou ◽  
Yun Zhou ◽  
Xiao-Feng Sun

e15102 Background:FBI-1 is a recently characterized proto-oncoprotein of the POZ domain Krüppel-like (POK) family of transcription factors. Although several studies provide the evidence that FBI-1 is an important gene regulator in CRC, no analysis of any correlation between FBI-1 expression and preoperative radiotherapy (RT) has been studied in rectal cancers. Methods: This study included the patients with rectal cancer that participated in a Swedish clinical trial of preoperative RT between 1987 and 1990. Patients were divided into preoperative RT (62) and non-RT (77) groups. Applying immunohistochemstry, we detected FBI-1 expression in 118 normal mucosa, 139 primary rectal cancers, and 45 lymph node metastases, and analyzed its relationship with clinicopathological features and RT response. Results: FBI-1 was detected both in the cytoplasm and nucleus, and the cytoplasmic staining was up-regulated compared with normal mucosa both in non-RT and RT groups (74.0% vs. 17.7%, p < 0.001; 69.4% vs. 41.1%, p = 0.002), however, the nuclear staining was down-regulated compared with normal mucosa both in non-RT and RT groups (22.1% vs. 75.8%, p < 0.001; 35.5% vs. 83.9% p < 0.001). Both cytoplasmic and nuclear staining were no difference between the non-RT and RT groups (74.0% vs. 69.4%, p = 0.542; 22.1% vs. 35.5%, p = 0.080, respectively). So we combined the non-RT and RT group together for further analysis. Nuclear staining of FBI-1 was positively with TNM stage and distance recurrence, it showed higher expression in III+ IV stage than that in I+II stage (41.0% vs. 17.9%, p = 0.003). The patients with distance recurrence showed higher FBI-1 expression than that with no distance recurrence (39.7% vs. 19.8%, p = 0.010). In stage I, II and III patients, higher nuclear FBI-1 in primary cancer showed worse disease free survival (HR: 1.934; 95%CI: 1.055-3.579, p = 0.033) and overall survival (HR: 2.174; 95%CI: 1.102-4.290; p = 0.025) independent of gender, age, growth pattern, differentiation and RT. Conclusions: Higher nuclear FBI-1 is related with later TNM stage, distance recurrence, and worse prognosis, it can be used as a potential diagnostic and prognostic biomarker in rectal cancer.


1997 ◽  
Vol 272 (5) ◽  
pp. E796-E802 ◽  
Author(s):  
W. H. Hartl ◽  
H. Demmelmair ◽  
K. W. Jauch ◽  
H. L. Schmidt ◽  
B. Koletzko ◽  
...  

Previous studies on human colorectal tumor protein synthesis in situ relied on techniques that required intra- or perioperative sampling to obtain a sufficient biopsy size. The purpose of the present study was to develop a new technique by use of new mass spectrometry equipment [capillary gas chromatography (GC)-combustion isotope ratio mass spectrometry (IRMS)], which allows reduction of the necessary sampling size. Thereby, tumor sampling could be done via conventional rectosigmoidoscopy, excluding the need for further disturbing invasive measures. Fifteen postabsorptive patients with localized rectal cancer received a primed-constant infusion of [1-13C]leucine (0.16 mumol.kg-1.min-1 constant, 9.6 mumol/kg prime). Forceps biopsies were taken after 3 and 6 h. In five subjects, tumor tissue and normal mucosa were studied simultaneously. Determination of protein-bound leucine enrichment was done by GC-IRMS, and GC-quadrupole MS was used to determine tracer-to-tracee ratios (tracer/tracee) for free intracellular leucine. GC-MS data demonstrated achievement of a steady state in the precursor pool enrichment after 3 h of isotope infusion (tracer/tracee at 3 h: 6.34 +/- 0.46%, at 6 h: 6.58 +/- 0.38%). Calculation of tumor protein synthesis yielded a fractional synthetic rate (FSR) of 1.06 +/- 0.11%/h or 25.5 +/- 2.6%/day (range 12.0-37.1%/day). At any time, protein-bound leucine enrichment was significantly higher in tumor tissue than in normal mucosa of the same subject. However, protein synthetic rates were comparable (tumor: 1.09 +/- 0.20%/h, mucosa: 1.29 +/- 0.28%/h). Thus combined GC-combustion IRMS and GC-/quadrupole MS provide a simple, reliable, and minimally invasive method to determine tumor FSR in situ, thereby excluding interferences common to previous methods. Tumor and mucosa tissues are similar with respect to protein synthesis, but they apparently differ with respect to leucine extraction from the arterial blood.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16096-e16096
Author(s):  
Pranitha Prodduturvar ◽  
Ben McCormick ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
Daisy E Escobar ◽  
...  

e16096 Background: Adenocarcinomas arising from the distal one third of the transverse colon, splenic flexure, descending colon, sigmoid colon and rectum are often grouped together due to their hindgut embryologic origin and referred to as left-sided colorectal cancer (CRC). Rectal cancer represents a subset of CRC that has distinct differences in anatomical location, clinical behavior, prognosis and molecular background. In patients with left sided colon cancer (LSCC), the expression of exosomal marker CD63 was reported to be higher in the adjacent normal mucosa (ANM) compared to the tumor (224 vs 154, p = 0.0001). Here, we explored the pattern of CD63 expression using immunohistochemistry in patients with rectal cancer in comparison with patients with LSCC. Methods: Between 2015 and 2018, 53 patients underwent rectal cancer biopsy/resection and had available tissues for CD63 IHC staining. Two pathologists independently scored CD63 expression in the tumor and ANM. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Paired t test was used for statistical analysis. Results: Median age was 60 (range 34-80). Females represented 26%. Caucasians and African Americans represented 74% and 26%, respectively. In patients with rectal cancer, the mean CD63 expression was higher in ANM compared to their expression in the tumor (147 vs 113, p = 0.0012). Compared to patients with LSCC (N = 30), the mean CD63 expression in patients with rectal cancer was lower in the ANM (224 vs 147, p < 0.0001) and in the tumor (154 vs 113, p = 0.01). Conclusions: In our cohort of patients with rectal cancer, exosomal marker CD63 expression was lower in tumor compared to ANM. This observation was similar to our previously reported findings in patients with LSCC. Compared to patients with LSCC, patients with rectal cancer had lower expression of CD63 in the tumor and ANM. To our knowledge, this is the first study to explore exosomal marker CD63 expression using IHC in patients with rectal cancer.


2016 ◽  
Vol 45 ◽  
pp. 98-107 ◽  
Author(s):  
Lila E. Mullany ◽  
Jennifer S. Herrick ◽  
Roger K. Wolff ◽  
John R. Stevens ◽  
Martha L. Slattery

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 101-101
Author(s):  
Moh'd M. Khushman ◽  
Pranitha Prodduturvar ◽  
Shalla Akbar ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
...  

101 Background: Exosomes mediate intercellular communications and have pivotal roles in cancer development. CD63 and CD9 are widely accepted exosomal markers. The effect of concurrent chemoradiation on the expression of exosomal markers is unknown. Here we explored the effect of neoadjuvant concurrent chemoradiation (NCCR) on exosomal markers (CD63 and CD9) expression in patients with locally advanced rectal cancer (LARC). Methods: Between 2015 and 2018, 33 patients had LARC treated with NCCR and had pre NCCR biopsy and post NCCR resected rectum examined for exosomal markers expression using immunohistochemistry. Two pathologists independently scored CD63 and CD9 staining in the tumor. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Un-Paired t test was used for statistical analysis. Results: In our cohort, median age was 59 years. Males represented 79% of the patients. Caucasians, African American and other ethnic groups represented 70%, 27% and 3% respectively.The mean tumor CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 106 vs 165 (p = 0.0022). The mean tumor CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 136 vs 215 (p < 0.0001). The exosomal markers expression in the adjacent normal mucosa (ANM) from pre NCCR biopsy and post NCCR resected rectum was only performed in16 out of 33 patients (due to ANM tissue availability). The mean ANM CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 166 vs 183 (p = 0.37). The mean ANM CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 104 vs 145 (p = 0.0897). Conclusions: In patients with LARC, the expression of exosomal markers (CD63 and CD9) increased after treatment with NCCR. Our results show that the expression of CD63 and CD9 is relatively higher in rectal cancer specimens treated with NCCR and thus suggest a possible role of these exosomes in adaptive response to NCCR. Further follow-up and laboratory studies are required to precisely understand the underlying mechanism(s).


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