Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients

Emerging evidence has implicated a pivotal role for lysyl oxidase (LOX) in cancer progression and metastasis. Whilst the majority of work has focused on the extracellular matrix cross-linking role of LOX, the exact function of intracellular LOX localisation remains unclear. In this study, we analysed the LOX expression patterns in the nuclei of rectal cancer patient samples and determined the clinical significance of this expression. Nuclear LOX expression was significantly increased in patient lymph node metastases compared to their primary tumours. High nuclear LOX expression in tumours was correlated with a high rate of distant metastasis and increased recurrence. Multivariable analysis showed that high nuclear LOX expression was also correlated with poor overall survival and disease free survival. Furthermore, we are the first to identify LOX enzyme isoforms (50 kDa and 32 kDa) within the nucleus of colon cancer cell lines by confocal microscopy and Western blot. Our results show a powerful link between nuclear LOX expression in tumours and patient survival, and offer a promising prognostic biomarker for rectal cancer patients.Funding agencies: Swedish Cancer Foundation; Research Council of South East Sweden; Liu Cancer</p

Пути развития дополнительного образования взрослых

ОБРАЗОВАНИЕ МЕДИЦИНСКОЕДОПОЛНИТЕЛЬНОЕ ОБРАЗОВАНИЕДОПОЛНИТЕЛЬНОЕ ОБРАЗОВАНИЕ ВЗРОСЛЫХОБРАЗОВАНИЕ МЕДИЦИНСКОЕ ПОСЛЕДИПЛОМНОЕ НЕПРЕРЫВНО

BCR/ABL-negative chronic myeloid leukemia with ETV6/ABL fusion

A BCR/ABL-negative chronic myeloid leukemia (CML) with t(12;14) (p12;q11-13) as the sole chromosomal abnormality was investigated by fluorescence in situ hybridization (FISH), which disclosed a cryptic insertion of ETV6 (previously called TEL), located at 12p12, into ABL at chromosome band 9q34. ETV6/ABL fusion was confirmed by RT-PCR, revealing that the first five exons of ETV6 were fused in frame with ABL at exon 2. Wild-type ETV6 was expressed, in accordance with the FISH results showing no deletion of the second ETV6 allele. ETV6/ABL chimeric transcripts have previously been reported in acute leukemias, but never before in CML. The present case suggests that ETV6/ABL positivity may constitute a new genetic subgroup of BCR-negative CML

Prognostic value of nuclear FBI-1 in patients with rectal cancer with or without preoperative radiotherapy

Factor that binds to the inducer of short transcripts of the human immunodeficiency virus-1 (FBI-1) represents as a crucial gene regulator in colorectal cancer; however, the correlation between FBI-1 and preoperative radiotherapy (RT) in rectal cancer (RC) has not yet been reported. The aim was to detect FBI-1 expression in patients with RC with or without RT, by immunohistochemistry and quantitative polymerase chain reaction, and to analyze its association with clinicopathological features and response to RT. The results from immunohistochemistry analysis (n=139) and reverse transcription-quantitative polymerase chain reaction (n=55) demonstrated that FBI-1 was overexpressed in patients with RC, whether they had received preoperative RT or not. Subsequently, the association between FBI-1 expression, and the clinicopathological features and response to RT in patients with RC was analyzed. Cytoplasmic FBI-1 was upregulated in non-RT (n=77) and RT (n=62) groups (17.7 vs. 74.0%, Pamp;lt;0.001; 41.1 vs. 69.4%, P=0.002, respectively) of patients with RC compared with normal mucosa. However, nuclear FBI-1 was downregulated (75.8 vs. 22.1%, Pamp;lt;0.001; 83.9 vs. 35.5%, Pamp;lt;0.001, respectively) in both groups. RT had no significant effect on FBI-1 expression in RC tissues. Furthermore, nuclear FBI-1 was positively associated with tumor-node-metastasis stage and distant recurrence (P=0.003 and P=0.010, respectively). In patients with stage I, II or III RC, higher nuclear FBI-1 expression was associated with poorer disease-free survival [hazard ratio (HR)=1.934, 95% confidence interval (CI): 1.055-3.579, P=0.033] and overall survival (HR=2.174, 95% CI: 1.102-4.290, P=0.025), independently of sex, age, growth pattern, differentiation and RT. In addition, FBI-1 was positively correlated with numerous biological factors, including p73 [Spearmans correlation coefficient (r(s))=0.332, P=0.007], lysyl oxidase (r(s)=0.234, P=0.043), Wrap53 (r(s)=-0.425, P=0.0002) and peroxisome proliferator-activated receptor delta (r(s)=-0.294, P=0.026). In conclusion, the present study demonstrated that nuclear FBI-1 was an independent prognostic factor in patients with RC and correlated with numerous biological factors, which indicated that it may have multiple roles in RC.Funding Agencies|National Natural Science Foundation of ChinaNational Natural Science Foundation of China [U1204818]; Projects of Science and Technology in Henan Province [172102310064, 201702195]; Swedish Cancer Foundation [3610-B06-11XCC]</p

Expressions of miR-302a, miR-105, and miR-888 Play Critical Roles in Pathogenesis, Radiotherapy, and Prognosis on Rectal Cancer Patients : A Study From Rectal Cancer Patients in a Swedish Rectal Cancer Trial of Preoperative Radiotherapy to Big Database Analyses

Differential expressions and functions of various micoRNAs (miRNAs) have been intensively studied in both colon and rectal cancers. However, the importance of miRNAs on radiotherapy (RT) response and clinical outcome in rectal cancer patients remains unclear. In this study, we used real-time polymerase chain reaction to examine the expressions of miR-302a, miR-105, and miR-888 in normal mucosa and cancer tissue from rectal cancer patients with and without preoperative RT. The biological function of miR-302a, miR-105, and miR-888 expression was further analyzed and identified through the public databases: TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis). The results showed that the expression of miR-105 in rectal cancer was higher than that in normal mucosa in RT (P= 0.042) and non-RT patients (P= 0.003) and was associated with mucinous histological type (P= 0.004), COX-2 (P= 0.042), and p73 expression (P= 0.030). The expression of miR-302a was shown more frequently in cancers with necrosis (P= 0.033) and with WRAP53 expression (P= 0.015), whereas miR-888 expression occurred more frequently in tumors with protein the expression of survivin (P= 0.015), AEG-1 (astrocyte elevated gene-1) (P= 0.003), and SATB1 (special AT-rich sequence binding protein 1) (P= 0.036). Moreover, TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. The miRNA-gene network analysis showed that ABI2 was associated with all the three miRNAs, with lower expression and good diagnostic value in rectal cancers. The TCGA database demonstrated the association of miR-105 expression with high carcinoembryonic antigen level (P= 0.048). RT reduced the expressions of miR-302a, miR-105, and miR-888. Prognostic analysis showed that miR-888 expression was independently associated with worse survival of patients without RT [overall survival,P= 0.001; disease-free survival,P= 0.009]. Analysis of biological function revealed that the protein serine/threonine kinase activity and PI3K-AKT signaling pathway were the most significantly enriched functions and pathways, respectively. Our findings suggest that miR-105 is involved in rectal cancer pathogenesis and miR-888 is associated with prognosis. MiR-302a, miR-105, and miR-888 have potential influence on the pathogenesis, RT, and prognosis of rectal cancer.Funding Agencies|Swedish Cancer Foundation; Swedish Research CouncilSwedish Research Council; Health Research Council in the South-East of Sweden [1921-B91-08XBC]</p

Efficacy of Surgery and Adjuvant Therapy in Older Patients With Colorectal Cancer A STROBE-compliant article

The present study aimed to assess the efficacy of surgery and adjuvant therapy in older patients (age greater than= 70 years) with colorectal cancer (CRC). Older CRC patients are under-represented in available clinical trials, and therefore their outcomes after receiving surgery and adjuvant therapy are unclear. From two prospective Swedish databases, we assessed a cohort of 1021 patients who underwent curative surgery for stage I, II, or III primary CRC, with or without adjuvant chemotherapy/ radiotherapy. Of the patients with colon cancer (n = 467), 182 (39%) were aged less than70 years, 162 (35%) aged 70 to 80 years, and 123 (26%) were aged greater than= 80 years. Of rectal cancer patients (n = 554), 264 (48%) were aged less than70 years, 234 (42%) aged 70 to 80 years, and 56 (10%) aged greater than= 80 years. Older patients with either colon or rectal cancer had higher comorbidity than did younger patients. Older patients with colon cancer had equivalent postoperative morbidity and 30-day mortality to younger patients. Rectal cancer patients aged greater than= 80 years had a higher 30-day mortality than younger patients (odds ratio OR], 2.37; 95% confidence interval CI], 1.6-4.55; P = 0.03). For either colon or rectal cancer, adjuvant chemotherapy compromised the 5-year overall survival (OS) of older patients with stage II disease and had no effect on those with stage III disease. Receiving adjuvant chemotherapy was a poor factor of OS for older patients with either colon (HR 1.88, 95% CI: 1.20-4.35, P = 0.03) or rectal cancer (HR 1.72, 95% CI: 1.052.26, P = 0.004). Preoperative short-course radiotherapy improved both OS and local control for older patients with stage III rectal cancer and had no effect on those with stage II disease. Radiotherapy was a favorable factor for the OS of the older patients with rectal cancer (HR 0.42, 95% CI: 0.21-3.57, P = 0.01). In conclusion, Older CRC patients had equal safety of surgery as younger patients, except rectal cancer patients aged greater than= 80 years that had a higher mortality. Adjuvant 5FU-based chemotherapy did not benefit older CRC patient, while neoadjuvant radiotherapy improved the prognosis of older patients with stage III rectal cancer.Funding Agencies|Swedish Cancer Foundation; Swedish Research Council; Health Research Council in the South-East of Sweden; Natural Science Foundation of China [81472304]</p

Gene Expression Profiling of Duodenal Biopsies Discriminates Celiac Disease Mucosa From Normal Mucosa

Celiac disease (CD) is identified by histopathologic changes in the small intestine which normalize during a gluten-free diet. The histopathologic assessment of duodenal biopsies is usually routine but can be difficult. This study investigated gene expression profiling as a diagnostic tool. A total of 109 genes were selected to reflect alterations in crypt-villi architecture, inflammatory response, and intestinal permeability and were examined for differential expression in normal mucosa compared with CD mucosa in pediatric patients. Biopsies were classified using discriminant analysis of gene expression. Fifty genes were differentially expressed, of which eight (APOC3, CYP3A4, OCLN, MAD2L1, MKI67, CXCL11, IL17A, and CTLA4) discriminated normal mucosa from CD mucosa without classification errors using leave-one-out cross-validation (n = 39) and identified the degree of mucosal damage. Validation using an independent set of biopsies (n = 27) resulted in four discrepant cases. Biopsies from two of these cases showed a patchy distribution of lesions, indicating that discriminant analysis based on single biopsies failed to identify CD mucosa. In the other two cases, serology support class according to discriminant analysis and histologic specimens were judged suboptimal but assessable. Gene expression profiling shows promise as a diagnostic tool and for follow-up of CD, but further evaluation is needed