bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression of micro-RNA in tumor and non-tumor tissues of patients with colorectal cancer.
Authors: Novikova Inna A. , Timoshkina Natalya N. , Kit Oleg Ivanovich , Poluektov Sergey I. , Dashkov Andrey V. , Haragezov Dmitry , Tolmakh Roman E. , Kolesnikov Evgeniy N. , Dontsov Vladimir A. , Petrov Dmitry S. , Soldatkina Natalya V. , Gevorkyan Yuriy A. , Kutilin Denis S. 
Published: May 2020

e13516 Background: The colorectal cancer (CRC) incidence is steadily increasing. Moreover, the problem of its early diagnosis remains unresolved due to the low specificity of known tumor markers, and the problem of creating new therapeutic approaches is due to the lack of a complete understanding of the mechanisms of regulation of gene expression in this oncopathology. The study of micro-RNAs (short non-coding RNAs that regulate gene expression) can be the solution to both problems. The aim of the study was to analyze micro-RNA differential expression in the tumor and non-tumor tissues of CRC patients. Methods: 5 patients with CRC (colon adenocarcinoma, G2) were selected for the multiple parallel micro-RNA sequencing. The mirVana miRNA Isolation Kit protocol was used to isolate small RNA fractions. The miRNA library was prepared using the TruSeq Small RNASample Preparation Kit. Sequencing of the nucleotide sequences of cDNA libraries was performed using a MiSeq (Illumina, USA). The copy numbers of micro-RNA were determined by comparing the nucleotide sequence of the sequenced molecules in each sample with the known nucleotide sequences of micro-RNA presented in the databases. When analyzing the differential expression of micro-RNA, the DESeq2 method implemented in R medium was used. Results: Six differentially expressed micro-RNAs were detected (p < 0.05): 2 that decrease expression (hsa-miR-143-3p,hsa-miR-26a-5p) and 4 increase expression in the tumor relative to non-tumor (hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p). The highest level of expression in both tumor and non-tumor tissue was observed for hsa-miR-143-3p, the lowest one for hsa-let-7i-5p. Moreover, the largest difference in micro-RNA expression in tumor tissue relative to non-tumor was shown for hsa-miR-92a-3p (4.5 times, p = 0.02), the smallest for hsa-miR-143-3p (2.4 times, p = 0.04). For miRNAs that differentially changed their expression, a search was made for target genes using the miRWalk 3.0 database. 14573 target genes were found, of which 3346 were for hypo-expressed micro-RNAs and 11228 for hyper-expressed micro-RNAs. Conclusions: Sequencing revealed 6 differentially expressed micro-RNAs (hsa-miR-143-3p, hsa-miR-26a-5p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p) in the tumor tissue is relatively non-tumor tissues of the colon. The data obtained expand the understanding of the mechanisms of gene regulation in the context of this oncopathology and may possibly become the basis for highly specific tumor markers panel.
Druggable fusion gene landscape in solid tumors.
Authors: Williams Gareth Haydn , Thatcher Robert Paul , Nevado Polo Borja , Haddow Tiffany Eira , Hardisty Keeda-Marie , Loddo Marco 
Published: May 2020

e13517 Background: Kinases activated by gene fusions represent an important class of oncogenes in solid tumors highlighted by the unique site agnostic FDA approval of larotrectinib for NTRK gene rearrangements. However, the frequency and types of druggable fusions in solid tumors are not well characterized from the clinical perspective. Methods: Oncofocus is a clinically validated precision oncology platform that includes analysis of 399 druggable driver-partner oncogenic fusion genes linked to 140 unique targeted therapy protocols. A retrospective analysis of Oncofocus trending data in a real-life cohort of 1111 patients has been used to determine the actionable fusion gene landscape in solid tumors. Results: Eighty nine actionable fusion genes were identified in 1111 samples of solid tumors linked to 73 targeted therapy protocols. Seven of the samples harbored multiple fusion genes. Eighty two of the 1111 samples tested had at least one actionable fusion gene representing a frequency of 7.38%. The highest frequency of actionable fusions were observed in glioblastoma (23%), head and neck (12%), kidney (11%) and prostate (10%) cancers. Four of the seven samples with multiple actionable fusions were found in glioblastoma. Pancreatic, lung and endometrial cancers and cancer of unknown primary (CUPs) had an actionable fusion gene frequency ranging from 7-9%. TBL1XR1-PIK3CA, MET-MET, WHSC1L1-FGFR1 and EGFR VIII fusions were identified as the most common druggable fusions. All actionable fusion genes were found to interact with one or more of the following pathways RAS/RAF/MEK/ERK, PI3K/AKT/MTOR, PLCy/PKC and JAK/STAT. Although a targeted agent for TRK fusions now has FDA approval, this rearrangement appears to be a rare event. In contrast, inhibitors targeting the TBL1XR1-PIK3CA, MET-MET, WHSC1L1-FGFR1 fusions and linked downstream signalling pathways appear to offer much broader clinical utility. Conclusions: Druggable fusions were identified at an unexpectedly high frequency and should therefore be included as part of routine comprehensive precision oncology testing. Notably, many of the actionable fusions are not tumor type specific reinforcing the “site agnostic” approach to profiling and supporting the concept of “molecular basket” clinical trials. Precision oncology trending data also provides actionable mutational landscapes which can be used to refine precision oncology testing, patient selection for targeted therapy protocols and enhancement of clinical trial design.
Genomic and epigenomic profiles to distinguish pulmonary enteric adenocarcinoma from lung metastatic colorectal cancer.
Authors: Wang Jie , Zuo Ying , Bai Hua , Duan Jianchun , Wang Zhijie , Li Weihua , Ying Jianming , Han Jie-Fei , Tian Yanhua , Chen Yedan , Shao Yang 
Published: May 2020

e13528 Background: As an extremely rare variant of lung adenocarcinoma, the diagnosis of pulmonary enteric adenocarcinoma (PEAC) remains challenging in the clinic due to shared morphological and immunohistochemical features with lung metastatic colorectal cancer (mCRC). Current differentiation of PEAC and mCRC mainly relies on clinical history and pathological examination while which still remain risks of misdiagnosis. Due to their distinct treatment regimens, effective molecular markers are essential for accurate diagnosis. However, comprehensive molecular features of PEAC is still poorly understood. Methods: We performed whole-exome sequencing and targeted bisulfite sequencing of 23 PEAC and 20 mCRC and matched normal tissue to improve molecular characterization. For DNA methylation profiling, differentially methylated regions (DMR) were analyzed by comparing PEAC with normal lung tissue and with mCRC. We also trained machine learning methods to distinguish PEAC from mCRC and validated the classifier in an independent cohort with 10 PEAC and 10 mCRC. Results: Mutations of KRAS, APC, and EGFR, alterations of chromosome arms 13q, 14q and 18p were found to be the major differential genetic alterations between PEAC and mCRC (P < 0.05), yet not enough to aid clinical diagnosis. For epigenomic profile, we identified 524 DMRs (false discovery rate ≤0.05) which were further reduced to 30 DMRs according to importance rank by the random forest algorithm. Based on these DMR features, we developed a diagnostic classifier that correctly classified 95.1% of patients in this discovery cohort. We further validated this predictive model in the validation cohort, with a prediction accuracy of 90.0%. We demonstrated its clinical application in two cases with difficulties to diagnosis by traditional methods. Conclusions: We have illustrated the unique genetic and methylation profiles of PEAC and mCRC. Our approach for disease classification may have a substantial impact on diagnostic precision and therapeutic decision for PEAC.
The effect of transcriptional activity of genes regulating DNA repair and apoptosis on the effectiveness of radiation therapy in rectal cancer patients.
Authors: Kosheleva Natalia G , Gusareva Marina A. , Udalenkova Irina A. , Rozenko Lyudmila Y. , Donskaya Aliya K. , Fatkina Natalya B. , Gabrichidze Peter N. , Solntseva Anna A. , Karnaukhova Elena A. , Krokhmal Julia N. , Vasilyeva Ekaterina O. , Kit Oleg Ivanovich , Kutilin Denis S. 
Published: May 2020

e13531 Background: Preoperative radiation therapy (RT) followed by surgery is the main effective treatment for colorectal cancer. However, some patients do not respond to preoperative RT due to the radioresistance of tumor cells, depending on their molecular characteristics, in particular on the expression of a certain group of genes. The aim of this work was to study the effect of expression of BRCA2, H2AX, RBBP8, CASP9 and BCL2 genes on the effectiveness of preoperative RT for rectal tumors. Methods: In the study, paired biopsy preparations (obtained by VCS before irradiation) of normal and tumor tissues of the rectum (adenocarcinoma G1-2) in 30 patients were used. RT was carried out on a Novalis TX linear accelerator (Varian, USA) (SFD = 2.4 Gy to TFD = 54 Gy). RNA isolation was performed by Chomczynski&Sacchi method. Reverta-L kits were used to synthesize cDNA libraries. Using the RT-qPCR method, the relative expression of 5 genes was determined: BRCA2, H2AX, CASP9, RBBP8 and BCL2 (reference GAPDH, ACTB and B2M). Statistical analysis was performed using the Shapiro–Wilk and Mann–Whitney criteria. Results: 2 clusters of patients were identified that differed in the expression of the BRCA2, H2AX, CASP9, RBBP8 and BCL2 genes. In cluster 1, 81% of patients had increased expression of the CASP9 gene and 100% decreased expression of the BRCA2, H2AX, RBBP8, and BCL2 genes. In cluster 2, the expression of the CASP9 gene was reduced in 100% of patients and the expression of the BRCA2, H2AX, RBBP8 and BCL2 genes was increased in 93%. A subsequent analysis of the results of RT showed that 16 patients had complete tumor regression after RT, while expression of the H2AX and RBBP8 genes was reduced by a factor of 2 (p < 0.05), and the expression of the CASP9 gene was increased by a factor of 4 (p < 0.005) relative to normal tissues. 8 patients showed slight tumor regression, and 6 patients had no regression at all, while their expression of the BRCA2, H2AX, RBBP8 and BCL2 genes was statistically significantly (p < 0.005) 2, 4, 6 and 3 times higher, respectively, and that of CASP9 gene was 4 times lower than in patients with complete tumor regression. Conclusions: The study found that the expression of BRCA2, H2AX, CASP9, RBBP8 and BCL2 genes affects the effectiveness of RT, enhancing it in patients with increased expression of CASP9 and reduced expression of H2AX and RBBP8, and vice versa, the effectiveness of therapy decreases with increased expression of H2AX, RBBP8, BRCA2 and BCL2.
Characteristics of breast cancer in Slovenian patients with germline CHEK2 c.444+1G>A mutation.
Authors: Besic Nikola , Blatnik Ana , Nizic-Kos Tea , Novakovic Srdjan , Krajc Mateja 
Published: May 2020

e13536 Background: Different CHEK2 germline pathogenic variants/likely pathogenic variants (PV/LPV) are associated with distinct immunophenotypic molecular subtypes of breast cancer (BC). The aim of our study was to explore the characteristics of Slovenian BC patients with CHEK2 c.444+1G > A variant. Methods: Germline CHEK2 pathogenic PV/LPV were identified in 76 individuals from 50 families who underwent genetic counseling and testing using a multigene panel at our institution from year 2014 to 2019. The data on 41 Slovenian BC patients with CHEK2 PV/LPV were retrospectively collected and analyzed, with an emphasis on c.444+1G > A variant carriers. Results: BC in our CHEK2 positive patients was diagnosed in 40 females and one male. Mean age at BC diagnosis was 42.8 years (range 21-63). Four recurrent CHEK2 PV/LPV were found in 80% (33/41) of our BC patients: c.444+1G > A (12/41; 29%; 11 females, one male), c.349A > G (9/41; 22%). deletion of exons 9-10 (7/41; 17%) and c.1100delC (5/41; 12%). There was a trend for c.444+1G > A carriers to develop BC at younger age in comparison to patients with other CHEK2 PV/LPV (mean age 39.3 vs. 44.2 years; p = 0.089). None of the patients with the c.444+1G > A variant had invasive lobular carcinoma. Median tumor size in patients with c.444+1G > A variant was 34 mm and median number of positive lymph nodes was 2.67 (range 1-8). Patients with c.444+1G > A variant had a luminal A subtype in 2 cases, luminal B in 7 cases, HER2+ subtype in 3 cases, while none of patients had a triple negative BC. Mastectomy, tumorectomy and axillary lymphadenectomy was performed in 8, 4 and 12 patients, respectively. All c.444+1G > A carriers had to be treated with chemotherapy and external beam irradiation. Patients with the c.444+1G > A variant were more often treated with chemotherapy (p = 0.038) and/or external beam irradiation (p = 0.014) in comparison to patients with other PV/LPV. Distant metastases were diagnosed in two patients at age 45 and 47. Conclusions: Mutation c.444+1G > A was detected in 29% of Slovenian patients with CHEK2 PV/LPV. Distant dissemination was diagnosed despite aggressive treatment at a young age in 16% of these patients.
Exploring African American males' attitudes towards genetic testing for prostate cancer risk.
Authors: Leader Amy , Fortune Thierry , Weddington Pamela , Crumpler Nicole , Giri Veda N. 
Published: May 2020

e13552 Background: African American (AA) males have disproportionately high prostate cancer (PCA) incidence and mortality rates compared to men of other races. While genetic testing for PCA is rapidly expanding, AA men represent fewer than 10% of those who undergo genetic counseling and testing. Barriers for AA males may include a lack of awareness or understanding, cultural beliefs, financial and access-to-care limitations, fear of discrimination, and mistrust in the healthcare system. These issues may be exacerbated among low-income, urban AA males. Methods: We conducted two focus groups with AA males who live in a low-resource neighborhood in a major US city to explore their understanding about PCA, challenges in obtaining and discussing family health history, and attitudes towards genetic counseling and testing. Prior to the start of the focus groups, men provided informed consent and completed a brief survey to capture demographic and health history information. Focus groups were moderated by a male member of the community, were audio and video recorded, and transcribed verbatim. Transcripts were analyzed using NVivo 12 to deduce themes within the discussions. Results: Seventeen men participated in one of two focus groups. The mean age was 54 years old (range: 40-66). Only 5 men (30%) were married. Ten men (60%) did not report a family history of PCA, while the remaining 7 reported that their father, grandfather, brother or uncle had PCA. All men had a primary care visit in the past 3 years, but only 13 out of 17 men (76%) reported discussing PCA. Focus group discussions and analyses revealed multiple key themes. Men had limited understanding of the prostate and PCA, with somewhat fatalistic views toward cancer. Family history was recognized as an important risk factor for cancer; talking about family history has become easier and more widely accepted. However, there was mixed reaction to genetic testing: most men were unfamiliar with it but were in favor of learning more, while a few did not see the utility of genetic information. Conclusions: AA men continue to have knowledge deficits about PCA. While there is strong understanding that cancer may be hereditary, there is less awareness about PCA genetic testing. Targeted genetic education and addressing access and cost barriers to genetic testing among AA males is needed to increase uptake of genetic testing and participation in genetic trials.
Treating obesity as primary prevention of cancer.
Authors: Ferdous Chowdhury , Islam Tareq 
Published: May 2020

e13556 Background: Prevalence of obesity in Hispanic population has been increasing. Obesity is a ‘super carcinogen’ and largely modifiable factor. We hypothesize due to current increase in prevalence of obesity there will be similar change in trend of malignancy among Hispanics and treating obesity can lead to decrease prevalence of both health conditions. Methods: National Health and Nutrition Examination Survey (NHANES) from year 1999 through 2016 was used to analyze obesity prevalence across different races. Surveillance Epidemiology and End Result (SEER) data was analyzed for racial distribution of overall and different kind of malignancies stratified by different races from 1999 through 2016. Differences of prevalence among different groups were calculated using likelihood ratio. Results: After exclusion criteria final sample size was 48,816 from NHANES and 6,868,226 from SEER dataset. Prevalence of obesity steadily increased in all races with highest change in Hispanics (31.7% in 1999-2000 to 47.3% in 2015-2016). Proportion of Hispanics with cancer also steadily increased from 7.5% in 1999-2000 to 11.3 in 2015-2016 in SEER dataset. States with high Hispanic population (New Mexico, California and New Jersey) had higher proportion of breast cancer (15.4%) compared to other states (14.5%) (p-value < 0.0001). Conclusions: Upward trend of obesity and malignancy is evident among Hispanic population. Hispanic populated states are showing higher prevalence of certain metabolically active malignancies. This increase in prevalence can be explained by “Migration Effect”. By intervening obesity 18% population attributable factor (PAF) is achievable. Opportunity exists to change this increasing trend in cancer epidemiology by treating obesity as primary prevention.
Dietary consumption of tea and the risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial.
Authors: Thomas Robert J. , McConnachie Alex , Stanley Bethany , Williams Madeleine 
Published: May 2020

e13559 Background: The popular beverage tea, brewed from infused leaves of camellia sinesis, contains non-phytoestrogenic polyphenols such as flavonoids, anthocyanidins, flavanols (epigallocatechin gallate); phenolic acids (ellagic acid) and stimulants (caffeine, theophylline). Laboratory studies report tea promotes antioxidant enzyme formation, slows cancer cell proliferation and unblocks apoptosis. Clinically, the Pomi-T randomised study reported tea extract (along with three other foods) reduced PSA progression in men with prostate cancer1. Evidence of prostate cancer prevention, however, from prospective cohort data is conflicting with one recent study even implying an increased risk2. Methods: We analysed 25,097 men within the intervention arm of the 155,000 participant PLCO screening trial. Histological confirmed cases of prostate cancer were reported in 3,088 men (12.3%) during the 11.5 year follow up. Tea consumption was assessed with a food frequency questionnaire (FFQ). Baseline characteristics were compared between groups using Chi-square and Kruskal-Wallis tests. Cox regression models were used to assess the association between tea intake and prostate cancer incidence. Results: Overall tea consumption was associated with a significantly lower risk of prostate cancer (p = 0.009). More precisely, the participants in the highest third of consumption group had a significantly lower risk compared to those in the lowest third (HR 1.16 (CI 1.05-1.29, p = 0.004). This pattern persisted with adjustments for age, sex, race and education level (p = 0.034), family history of cancer (p = 0.037). Those who never drank tea, however, had no statistical lower risk of prostate cancer compared to other groups (p = 0.501). Conclusions: Among tea drinkers, this data revealed a positive association between drinking tea and a reduced risk of prostate cancer. This data supports the consideration of future prospective intervention studies investigating the role of tea as part of a prostate cancer prevention programme. 1. Thomas et al. The NCRN Pomi-T RCT. Prostate cancer & prostatic diseases (2014), 2,180. 2. Reger et al. Dietary isoflavones and prostate cancer risk. Int J. Cancer (2017), 142; 4, 719.
Dietary intake of broccoli and the risk of cancer in the prostate, lung, colorectal, and ovarian cancer (PCLO) screening trial.
Authors: Thomas Robert J. , McConnachie Alex , Williams Madeleine M A , Stanley Bethany 
Published: May 2020

e13560 Background: The cruciferous vegetable broccoli, are a good source of vitamins, minerals and fibre, as well as thiol phytochemicals (indole-3-carbinol), glucosinolates (isothiocyanates, its metabolite, sulforaphane), carotenoids (lutein and zeaxanthin) and flavonols (kaempferol). Laboratory and human biopsy studies have found that broccoli intake influenced epigenetic expression of genes via blockage of histone deacetylase which reduce inflammation and cancer growth. Clinically, a randomised control study reported dried broccoli extract (along with three other foods) influenced PSA progression in men with prostate cancer1. However, no preventative intervention studies in humans have been conducted and data from cohort studies are inconsistent for its influence on cancer incidence2,3. Methods: We analysed 49,104 people within the intervention arm of the 155,000 participant PLCO screening trial. Histological confirmed cases of any cancer were reported in 8,263 (16.83%) during the 11.5 year follow up. Broccoli consumption was assessed with a food frequency questionnaire (FFQ). Baseline characteristics were compared between broccoli consumption groups using Chi-square and Kruskal-Wallis tests. Cox regression models were used to assess the association between broccoli intake and cancer incidence. Results: Broccoli consumption was associated with reduced cancer incidence: HR 0.95 (CI 0.93-0.97, p < 0.001). This pattern persisted with adjustments for age, sex, race, education level and family history (HR 0.97, CI 0.96-0.99, p = 0.007) as well as smoking, BMI and alcohol consumption (HR 0.98, CI 0.96-0.99, p = 0.010). Conclusions: The study identified an association between increased broccoli consumption and reduced cancer risk. In practical terms, 15g of broccoli, or more, consumed per day (about a small cup) was associated with a 5% lower risk of cancer. Broccoli should continue to be included in healthy eating advice. This data supports the consideration of future prospective intervention studies investigating the role of broccoli as part of a cancer prevention programme. References 1. Thomas et al. The NCRN Pomi-T RCT. Prostate cancer & prostatic diseases (2014), 2,180. 2. Liu et al Cruciferous vegetables inversely linked with breast cancer: Breast (2013), 22;3,309. 3. Bosetti et al Cruciferous vegetables and cancer risk Ann Oncol (2012) 23(8);2198.