Top 9 Biorxiv Papers Today in Cancer Biology


2.026 Mikeys
#1. Cancer/Testis Antigens Differentially Expressed In Indolent And Aggressive Prostate Cancer: Potential New Biomarkers And Targets For Immunotherapies
Luciane Kagohara, Neil M Carleton, Sayuri Takahashi, Takumi Shiraishi, Steven M Mooney, Robert L Vessella, Robert H Getzenberg, Prakash Kulkarni, Robert W Veltri
Current clinical tests for prostate cancer (PCa), such as the PSA test, are not fully capable of discerning patients that are highly likely to develop metastatic prostate cancer (MPCa). Hence, more accurate prediction tools are needed to provide treatment strategies that are focused on the different risk groups. Cancer/testis antigens (CTAs) are expressed during embryonic development and present aberrant expression in cancer making them ideal tumor specific biomarkers. Here, the potential use of a panel of CTAs as a biomarker for PCa detection as well as metastasis prediction is explored. We initially identified eight CTAs (CEP55, NUF2, PAGE4, PBK, RQCD1, SPAG4, SSX2 and TTK) that are differentially expressed in MPCa when compared to local disease and used this panel to compare the gene and protein expression profiles in paired PCa and normal adjacent prostate tissue. We identified differential expression of all eight CTAs at the protein level when comparing 80 paired samples of PCa and the adjacent non-cancer tissue. Using...
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biorxivpreprint: Cancer/Testis Antigens Differentially Expressed In Indolent And Aggressive Prostate Cancer: Potential New Biomarkers And Targets For Immunotherapies https://t.co/2up1YG19jZ #bioRxiv
biorxiv_cancer: Cancer/Testis Antigens Differentially Expressed In Indolent And Aggressive Prostate Cancer: Potential New Biomarkers And Targets For ... https://t.co/y5LLWlRcpC #biorxiv_cancer
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Authors: 9
Total Words: 0
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2.026 Mikeys
#2. Circulating bacterial DNA as a tool towards non-invasive biomarkers for colorectal cancer and adenoma
Qian Xiao, Wei Lu, Xiangxing Kong, Yang W. Shao, Yeting Hu, Ao Wang, Hua Bao, Kaihua Liu, Xiaonan Wang, Xue Wu, Shu Zheng, Ying Yuan, Kefeng Ding
Objective: The gut microbiota is closely associated with colorectal neoplasia. While most metagenomics studies utilized fecal samples, circulating microbial DNA in colorectal neoplasia patients remained unexplored. This study aimed to characterize microbial DNA in plasma samples Design: We performed whole genome sequencing of plasma samples from 25 colorectal cancer (CRC) patients, 10 colorectal adenoma (CRA) patients and 22 healthy controls (HC). Microbial DNA was obtained by removing the host genome and relative abundance was measured by mapping reads into microbial genomes. Significant biomarker species were identified in the discovery cohort and built into a random forest model, which was tested in the validation cohort. Results: In the discovery cohort, there were 127 significant species between CRC patients and HC. Based on the random forest model, 28 species were selected from the discovery cohort (AUC=0.944) and yielded an AUC of 1 in the validation cohort. Interestingly, relative abundance of most biomarker species in CRA...
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biorxivpreprint: Circulating bacterial DNA as a tool towards non-invasive biomarkers for colorectal cancer and adenoma https://t.co/RFaFTiPkxF #bioRxiv
biorxiv_cancer: Circulating bacterial DNA as a tool towards non-invasive biomarkers for colorectal cancer and adenoma https://t.co/k7dZwgoGaF #biorxiv_cancer
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Authors: 13
Total Words: 0
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2.026 Mikeys
#3. Image-based consensus molecular subtype classification (imCMS) of colorectal cancer using deep learning
Korsuk Sirinukunwattana, Enric Domingo, Susan Richman, Keara L Redmond, Andrew Blake, Clare Verrill, Simon J Leedham, Aikaterini Chatzipli, Claire Hardy, Celina Whalley, Chieh-Hsi Wu, Andrew D Beggs, Ultan McDermott, Philip Dunne, Angela A Meade, Steven M Walker, Graeme I Murray, Leslie M Samuel, Matthew Seymour, Ian Tomlinson, Philip Quirke, Tim Maughan, Jens Rittscher, Viktor Koelzer
Image analysis is a cost-effective tool to associate complex features of tissue organisation with molecular and outcome data. Here we predict consensus molecular subtypes (CMS) of colorectal cancer (CRC) from standard H&E sections using deep learning. Domain adversarial training of a neural classification network was performed using 1,553 tissue sections with comprehensive multi-omic data from three independent datasets. Image-based consensus molecular subtyping (imCMS) accurately classified CRC whole-slide images and preoperative biopsies, spatially resolved intratumoural heterogeneity and provided accurate secondary calls with higher discriminatory power than bioinformatic prediction. In all three cohorts imCMS established sensible classification in CMS unclassified samples, reproduced expected correlations with (epi)genomic alterations and effectively stratified patients into prognostic subgroups. Leveraging artificial intelligence for the development of novel biomarkers extracted from histological slides with molecular and...
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biorxivpreprint: Image-based consensus molecular subtype classification (imCMS) of colorectal cancer using deep learning https://t.co/gbYCU6tXCN #bioRxiv
biorxiv_cancer: Image-based consensus molecular subtype classification (imCMS) of colorectal cancer using deep learning https://t.co/7kLZb77gtG #biorxiv_cancer
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Authors: 24
Total Words: 0
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2.008 Mikeys
#4. miR-26a regulates extracellular vesicle secretion from prostate cancer cells via targeting SHC4, PFDN4 and CHORDC1
Fumihiko Urabe, Nobuyoshi Kosaka, Yurika Sawa, Tomofumi Yamamoto, Yusuke Yamamoto, Kagenori Ito, Takahiro Kimura, Shin Egawa, Takahiro Ochiya
Extracellular vesicles (EVs) are known to be involved in intercellular communication during cancer progression; thus, elucidating the detailed mechanism will contribute to the development of a novel strategy for EV-targeted cancer treatment. However, the biogenesis of EVs in cancer cells is not completely understood. MicroRNAs (miRNAs) regulate a variety of physiological and pathological phenomena; thus, miRNAs could regulate EV secretion. Here, we performed high-throughput miRNA-based screening to identify the regulators of EV secretion using an ExoScreen assay. By using this miRNA-based screening, we identified miR-26a, which was reported as a tumor suppressive miRNA, as a miRNA involved in EV secretion from prostate cancer (PCa) cells. In addition, we found that the SHC4, PFDN4, and CHORDC1 genes regulate EV secretion in PCa cells. Suppression of these genes by siRNAs significantly inhibited the secretion of EVs in PCa cells. Furthermore, the progression of PCa cells was inhibited in an in vivo study. On the other hand,...
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hanta73: マイクロRNAを使ったスクリーニング法でエクソソーム分泌に関わる新たな遺伝子を見つけました!さらにこれらの遺伝子はがんの悪性化に関わっていることも示しています。 興味のあるかたは、是非読んでコメントください! https://t.co/dW8YPgBn9p
hanta73: My first paper submitted in bioRxiv as corresponding author! Showing the novel molecules regulating exosome secretion by microRNA based screening. https://t.co/dW8YPgBn9p
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Sample Sizes : [3, 3, 3, 3, 3, 3, 3, 3, 3, 6, 18, 3, 3, 3, 3, 3, 3, 6]
Authors: 9
Total Words: 8770
Unqiue Words: 2334

1.998 Mikeys
#5. Regulation of KRAS4A/B splicing in cancer stem cells by the RBM39 splicing complex.
Wei-Ching Chen, Minh D. To, Peter M.K. Westcott, Reyno Delrosario, Il-Jin Kim, Mark Phillips, Quan Tran, Nora Bayani, Allan Balmain
The KRAS oncogene is expressed as major KRAS4B and minor KRAS4A splice isoforms, the distinct functions of which in cancer are unknown. We demonstrate here that KRAS4A is enriched in cancer stem-like cells, and is activated by hypoxia, whereas KRAS4B is more widely expressed and responds to ER stress. Mice completely lacking either isoform are viable but resistant to lung cancer development, as are Kras4A/B double heterozygous mice expressing both isoforms, but in which splice regulation has been uncoupled. Splicing of KRAS4A, but not KRAS4B, in human tumor cells can be inhibited by treatment with the splice inhibitor indisulam, or by CRISPR/Cas inhibition of the RBM39 splicing complex. Our data suggest that control of KRAS4A/B splicing is a targetable vulnerability in KRAS mutant tumors.
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tp_hernandez: RT @biorxivpreprint: Regulation of KRAS4A/B splicing in cancer stem cells by the RBM39 splicing complex. https://t.co/1hKNPhA4Wd #bioRxiv
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Sample Sizes : [10, 5]
Authors: 9
Total Words: 9689
Unqiue Words: 2717

1.997 Mikeys
#6. Cooperating lineage factors SOX2 and BRN2 govern the transcriptional program of the neural subtype of lung squamous cell carcinoma
Takashi Sato, Seungyeul Yoo, Ranran Kong, Maya Fridrikh, Abhilasha Sinha, Prashanth Chandramani-Shivalingappa, Ayushi Patel, Osamu Nagano, Takashi Masuko, Mary Beth Beasley, Charles A Powell, Jun Zhu, Hideo Watanabe
Lung squamous cell carcinoma (LUSC) is one of the major subtypes of lung cancer, molecular characterization of which has not sufficiently improved its treatment strategies. Accumulating evidence suggests that lineage-specific transcriptional regulators control differentiation states not only during normal development but also during cancer evolution. By investigating the super-enhancer landscape of LUSC, we identified a unique 'neural' subtype defined by Sox2 and a neural lineage factor Brn2. Robust protein-protein interaction and genomic co-occupancy of these factors indicated their transcriptional cooperation in this 'neural' LUSC in contrast to the cooperation of Sox2 and p63 in the classical LUSC. Introduction of p63 expression in the 'neural' LUSC invoked the classical LUSC lineage accompanied by Brn2 downregulation and increased activities of ErbB/Akt and MAPK-ERK pathways. Collectively, our data demonstrate a unique LUSC lineage featured by Sox2 cooperation with Brn2 instead of p63, for which distinct therapeutic approaches...
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Authors: 13
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1.997 Mikeys
#7. A rectal cancer model establishes a platform to study individual responses to chemoradiation
Karuna Ganesh, Chao Wu, Kevin P. O'Rourke, Mohammad Adileh, Bryan C. Szeglin, Isaac Wasserman, Michael R. Marco, Maha Shady, Youyun Zheng, Wouter R. Karthaus, Helen H. Won, Seo-Hyun Choi, Raphael A. Pelossof, Afsar Barlas, Emmanouil Pappou, Arthur Elghouayel, James S. Strong, Chin-Tung Chen, Jennifer W. Harris, Martin R. Weiser, Garrett M. Nash, Jose G. Guillem, Iris H. Wei, Andrea Cercek, Richard N. Kolesnick, Katia O. Manova-Todorova, Leonard B. Saltz, Ronald P. DeMatteo, Joan Massagué, Paul B. Romesser, Philip B. Paty, Rona D. Yaeger, Hans Clevers, Michael F. Berger, Jinru Shia, Scott W. Lowe, Lukas E. Dow, Julio Garcia-Aguilar, Charles L. Sawyers, Jesse Joshua Smith
Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation, and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to individual patients. We established a biorepository of 32 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic, or recurrent disease. RC tumoroids retained molecular features of the tumors from which they were derived, and their ex vivo responses to clinically relevant chemotherapy and radiation treatment correlate well with responses noted in individual patients' tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive rectal cancer followed by metastasis to lung and liver. Importantly, engrafted tumors closely reflected the heterogenous sensitivity to chemotherapy observed clinically. Thus, the biology and drug sensitivity of RC clinical isolates can be efficiently interrogated using an organoid-based, in vitro platform coupled...
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Authors: 40
Total Words: 13128
Unqiue Words: 3631

1.992 Mikeys
#8. MBOAT7-Driven Phosphatidylinositol Remodeling Promotes the Progression of Clear Cell Renal Cell Carcinoma.
Chase K. A. Neumann, Renliang Zhang, Daniel J. Silver, Varadharajan Venkaleshwari, C. Alicia Traughber, Christopher Przybycin, Defne Bayik, Jonathan D. Smith, Justin D. Lathia, Brian I. Rini, J. Mark Brown
The most common kidney cancer, clear cell Renal Cell Carcinoma (ccRCC) is closely associated with obesity. In fact, the clear cell variant of RCC is given this name due to large lipid droplets within the tumor cells. Although it is well appreciated that renal lipid metabolism is altered in ccRCC, the mechanisms driving this are not well understood. Leveraging a shotgun lipidomics approach we have identified a lipid signature for ccRCC that includes an increase in arachidonic acid-enriched phosphatidylinositols (AA-PI). In parallel, we found that ccRCC tumors have increased expression of the acyltransferase enzyme membrane bound O-acyltransferase domain containing 7 (MBOAT7) that contributes to AA-PI synthesis. In ccRCC patients, MBOAT7 expression increases with tumor grade, and increased MBOAT7 expression correlates with poor survival. Genetic deletion of MBOAT7 in ccRCC cells decreases proliferation and induces cell cycle arrest, and MBOAT7-/- cells fail to form tumors in vivo. RNAseq of MBOAT7-/- cells identified alterations in...
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Authors: 11
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1.955 Mikeys
#9. Robust genetic interactions in cancer are enriched in protein-protein interaction pairs
Christopher J Lord, Colm J Ryan
Genetic interactions, where the mutation of one gene can be associated with altered sensitivity to the inhibition of another gene, can be exploited for the development of targeted therapies in cancer. Many large-scale genetic perturbation screens in tumour cell lines have been used to identify such genetic interactions, including both synthetic lethal and resistance relationships. Despite these efforts, relatively few of the candidate genetic interactions identified have been reproduced across multiple studies. Here, we develop a computational approach to identify genetic interactions that can be reproduced across independent experiments and across non-overlapping cell line panels. We identified 220 such robust genetic interactions and found that they are enriched for gene pairs whose protein products physically interact. This suggests that protein-protein interaction networks may be used not only to understand the mechanistic basis of genetic interaction effects, but also to prioritise robust candidates for further development.
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