New insights to the clinical implication of HOXA5 as prognostic biomarker in patients with colorectal cancer

2020 ◽  
pp. 1-9
Author(s):  
Hamza Yaiche ◽  
Haifa Tounsi-Kettiti ◽  
Nadia Ben Jemii ◽  
Amira Jaballah Gabteni ◽  
Najla Mezghanni ◽  
...  

BACKGROUND: Homeobox A5 (HOXA5) is a member of the HOX protein family which is involved in several pathways of carcinogenesis, and is dysregulated in many types of cancers. However, its expression and function in human colorectal cancer (CRC) is still largely unknown. OBJECTIVE: This study, aimed to evaluate HOXA5 expression in Tunisian patients with CRC in order to define new potential biomarker. METHODS: An immunohistochemical study using an HOXA5 antibody was performed on 85 formalin fixed paraffin embedded specimens from patients with CRC. Six normal colon mucosa cases were used as controls. RESULTS: HOXA5 expression showed a cytoplasmic staining in both tumor and stromal/endothelial cells. Loss or low HOXA5 expression was seen in tumor cells in 74/85 cases (87.06%) and in stromal/endothelial cells, in 77/85 (90.59%). In control group of normal colon mucosa HOXA5 was moderately expressed in all the cases. The abnormal expression, was significantly associated to lymph nodes metastasis in tumor cells (p= 0.043) and in stromal/endothelial cells (p= 0.024). CONCLUSION: In our series, HOXA5 immunostaining suggests the valuable role of this protein in colorectal carcinogenesis. Moreover, the association of lymph node metastasis to HOXA5 abnormal expression underlies its crucial role in colorectal cancer dissemination and prognosis.

2017 ◽  
Vol 41 (2) ◽  
pp. 722-730 ◽  
Author(s):  
Adriana Mika ◽  
Jaroslaw Kobiela ◽  
Aleksandra Czumaj ◽  
Michał Chmielewski ◽  
Piotr Stepnowski ◽  
...  

Backgrounds/Aims: Colorectal cancer (CRC) cells show some alterations of lipid metabolism. Elongation of fatty acids (FA) has not been studied in CRC tissues thus far. The aim of this study was to verify if CRC specimens and normal colon mucosa differ in terms of their levels of very long-chain FAs, a product of FA elongation. Moreover, the expression of elongase genes has been studied in normal tissue and CRC. Finally, we searched for some specific products of FA elongation in serum of CRC patients. Methods: The specimens of normal colon mucosa and CRC were obtained from nineteen CRC patients differ in terms of FA elongation. We also searched for some specific products of FA elongation in serum of CRC patients and from healthy volunteers. Tissue and serum FA profiles were determined by means of gas chromatography-mass spectrometry (GC/MS), and the tissue expression of elongases (ELOVLs) was analyzed with real-time PCR. Results: Compared to normal colon tissue, CRC specimens showed significantly higher levels of 22-, 24- and 26-carbon FAs, stronger expressions of ELOVL1 and ELOVL6 (4- and 9-fold elevated respectively), and higher values of 18: 0/16: 0 elongation index. We also demonstrated presence of cerotic acid (26: 0) in serum of all CRC patients but in none of the healthy controls. Conclusions: CRC tissue seems to be characterized by enhanced FA elongation (hyper-elongation). Presence of cerotic acid in CRC patients sera and absence of this FA in healthy subjects points to this compound as a strong candidate for specific metabolic marker of colorectal malignancies.


Epigenomics ◽  
2020 ◽  
Vol 12 (16) ◽  
pp. 1389-1403
Author(s):  
Margareta Žlajpah ◽  
Emanuela Boštjančič ◽  
Nina Zidar

Aim: To identify (epi)genetic regulators of osteopontin (OPN, encoded by SPP1 gene) from normal colon mucosa to adenoma, adenoma with early carcinoma and advanced carcinoma. Patients & methods: Biopsy samples of 41 patients with different patohistologic diagnosis were used. Using qPCR, pyrosequencing and statistical analysis, we determined the expression level of osteopontin regulatory miRNAs, its copy number and methylation status. Results & conclusion: We showed that hsa-miR-146a-5p expression is inversely proportional to the expression level of SPP1 and that expression might be also controlled by copy number and methylation. These results suggest that not only expression of SPP1 but also its copy number, methylation status and expression of its regulators might be used as a potential biomarker of colorectal cancer.


2011 ◽  
Vol 23 (4) ◽  
pp. 276-282 ◽  
Author(s):  
Qing Xia ◽  
Ya Ding ◽  
Xiao-jun Wu ◽  
Rui-qing Peng ◽  
Qiang Zhou ◽  
...  

Oncotarget ◽  
2015 ◽  
Vol 6 (27) ◽  
pp. 23820-23836 ◽  
Author(s):  
Changhua Zhuo ◽  
Qingguo Li ◽  
Yuchen Wu ◽  
Yiwei Li ◽  
Jia Nie ◽  
...  

2020 ◽  
pp. jclinpath-2020-207008 ◽  
Author(s):  
Carlos A Rubio ◽  
Peter T Schmidt

ObjectiveSessile serrated lesions without dysplasia (SSL-ND) are epitomised by dilated crypts with epithelial serrations and architectural distortions portraying boot-shapes, L-shapes or inverted-T shapes. Recently, crypts in asymmetric fission were detected in SSL-ND. The purpose was to assess the frequency of crypts in asymmetric fission in a cohort of SSL-ND.MethodsThe frequency of crypts in fission was assessed in 60 SSL-ND, the distribution of cell proliferation in 48 SSL-ND and the expression of maspin, a tumour-suppressor protein, in 29 SSL-ND.ResultsOut of the 60 SSL-ND, 40 (66.7%) showed crypts in fission: 39 (65%) SSL-ND had crypts in asymmetric fission and one SSL-ND (1.7%), in symmetric fission (p<0.05). Of 1495 crypts recorded in the 60 SSL-ND, 73 (4.9%) were in asymmetric fission but only one (0.06%), in symmetric fission (p<0.05). Out of the 48 Ki67-immunostained SSL-ND,15 (31%) showed randomly distributed proliferating cell-domains. All 29 SSL-ND revealed maspin-upregulation (including crypts in asymmetric and symmetric fission). In contrast, the normal colon mucosa showed occasional single crypts in symmetric fission, proliferating cell-domains limited to the lower thirds of the crypts, absence of crypts in asymmetric fission and remained maspin negative.ConclusionsSSL-ND thrive with crypts in asymmetric fission displaying randomly distributed proliferating cell-domains and maspin-upregulation. These histo-biological aberrations disclose pathological cryptogenesis and suggest possibly unfolding somatic mutations in SSL-ND. The present findings may open new vistas on the parameters pertinent to the susceptibility of SSL-ND to develop dysplasia and carcinoma.


1987 ◽  
Vol 26 (2) ◽  
pp. 184-188 ◽  
Author(s):  
Akira TARI ◽  
Yukitaka MIYACHI ◽  
Koji SUMII ◽  
Goro KAJIYAMA ◽  
Akima MIYOSHI

Tumor Biology ◽  
2001 ◽  
Vol 22 (6) ◽  
pp. 383-389 ◽  
Author(s):  
S. Papadopoulou ◽  
A. Scorilas ◽  
N. Arnogianaki ◽  
B. Papapanayiotou ◽  
A. Tzimogiani ◽  
...  

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 395-395 ◽  
Author(s):  
Loes Scholten ◽  
Leon W. M. M. Terstappen ◽  
Job van der Palen ◽  
Walter Mastboom ◽  
Arjan Tibbe ◽  
...  

395 Background: The presence of circulating tumor cells (CTC) is associated with poor prognosis in patients with metastatic colorectal cancer (CRC). The current study was conducted to determine if the presence of CTC prior to surgery in patients with newly diagnosed non-metastatic CRC can identify those patients at risk for disease recurrence. Methods: In a prospective single center study 180 patients with newly diagnosed non-disseminated CRC scheduled for surgery were enrolled and followed up for a median of 41 months. CTC were enumerated with the CellSearch System in 4 aliquots of 7.5 ml of peripheral blood before undergoing surgery. The control group consisted of sixty patients with benign tumors after surgery or colonoscopy. Results: ≥1 CTC/ 30ml of blood were detected in 9 (15%) persons of the control group, and in 41 (23%) CRC patients. From the 180 CRC patients, 44 developed recurrent disease (24%) and 38 patients (21%) died during follow up. Presence of CTC correlated with disease recurrence (p= 0.040) and death (p=0.006). Patients with CTC had a significantly decreased three year Disease Free Survival (DFS) and overall survival (OS) versus those without CTC (DFS 57%vs. 78%, p=0.018 and OS 70% vs. 80%, p=0.003%). Conclusions: Patients with stage I-III CRC with CTC before surgery have a significantly lower 3 years DFS and OS. These findings warrant further development of technology to increased the sensitivity and specificity of CTC detection for incorporation as prognostic marker along side Duke Stage to assess which patients need adjuvant treatment.


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