Abstract 1553: Rho guanine nucleotide exchange factor (ARHGEF) 10 is a putative tumor suppressor in pancreatic ductal adenocarcinoma
Bibliographic record
Abstract
Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of pancreatic malignancies, and is the fourth leading cause of cancer related deaths. Disease prognosis is quite poor, with less than 20% of patients eligible for curative surgical resection at time of diagnosis and overall survival rates of 2%. PDAC arises from the malignant transformation of ductal epithelial cells through progressive accumulation of loss of function mutations and deletions of tumor suppressor genes. Chromosome 8p has been shown to be a recurrent site of deletions in PDAC. Among the deleted genes is the Rho guanine nucleotide exchange factor 10 (ARHGEF10), a regulator of Rho signaling that is involved in mitotic spindle formation. Here, we evaluate ARHGEF10 for its potential role as a tumor suppressor in PDAC. Methods: ARHGEF10 expression was assessed in 19 PDAC cell lines and in 53 patient tumor xenograft samples at both mRNA and protein levels. Publically available datasets were also used to determine correlation between ARHGEF10 mRNA expression and DNA copy number. After identifying PDAC cell lines with low ARHGEF10 expression, ARGHEF10 was stably overexpressed in these cell lines by lentiviral transduction. The effects of ARHGEF10 expression were then evaluated by in vivo tumorigenicity in immunodeficient mice, and by in vitro cell proliferation and cell motility wound healing assays. Results: ARHGEF10 showed reduced expression in up to 70% of cell lines and patient tumor xenografts. Reduced ARHGEF10 expression correlated significantly with loss of copy number in PDAC cell lines. Stable overexpression of ARHGEF10 in PDAC cell lines significantly reduced tumor growth in immunodeficient mice. In addition, ARHGEF10 expression resulted in decreased cell motility in wound healing assays, but had minimal effect on cell proliferation. Experiments for in vitro assessment of invasion and changes in Rho activity are ongoing, and will be presented Conclusions: This study suggests that ARHGEF10 may function as a tumor suppressor gene in PDAC. Citation Format: Joella Joseph, Nikolina Radulovich, Ming-Sound Tsao. Rho guanine nucleotide exchange factor (ARHGEF) 10 is a putative tumor suppressor in pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1553. doi:10.1158/1538-7445.AM2014-1553
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".