Abstract 3621: Identification of podocalyxin-positive tumor buds in pancreatic ductal adenocarcinoma: Implications for solid tumor collective invasion
Bibliographic record
Abstract
Abstract High expression of the single-pass transmembrane sialomucin, podocalyxin, has been shown to predict poor disease outcome in a number of solid tumor types, including pancreatic ductal adenocarcinoma (PDAC) (Taniuchi et al., 2016). In addition to the classical TMN staging measures of disease progression (tumor size, lymph node involvement, and distant metastasis) local invasion at the primary tumor site is a valuable indicator of solid tumor progression. Local invasion has been observed histologically as tumor buds, defined by the presence of small cohesive clusters of tumor cells in the invasive tumor-stromal interface. To date, tumor budding has been characterized as an indicator of poor prognostic outcome in colorectal carcinoma (CRC), pancreatic ductal adenocarcinoma (PDAC), invasive ductal breast carcinoma (IDC), lung adenocarcinoma (LUA), stomach and esophageal carcinomas, oral squamous cell carcinoma, periampullary adenocarcinoma, and head and neck squamous cell carcinoma (HNSCC). Our group has previously modelled tumor budding experimentally using the MCF7 human breast cancer cell line (Graves et al., 2016). We showed that forced over-expression of podocalyxin was a driver of local collective invasion and tumor budding in vitro and in vivo. Because podocalyxin is highly expressed in PDAC we sought to determine if its expression was involved in the process of tumor budding in this tumor context as well. We assessed large format histological sections from a cohort of patient PDAC tumors and identified high podocalyxin expression in tumor buds. Further, we generated podocalyxin-null MiaPaCa2 PDAC cell lines and demonstrated that podocalyxin-expression is required for collective invasion in 3D culture conditions. We are currently evaluating in vivo xenograft tumor models with these podocalyxin-expressing and podocalyxin-null MiaPaCa2 cells to determine whether changes in 3D culture invasion are representative of tumor budding in this model. Expression of podocalyxin by tumor buds provides rationale to support investigation into the impact of therapeutically targeting these invasive cells. Citation Format: Erin M. Bell, Steve E. Kalloger, Pamela M. Dean, Janel L. Kopp, Kelly M. McNagny, Calvin D. Roskelley. Identification of podocalyxin-positive tumor buds in pancreatic ductal adenocarcinoma: Implications for solid tumor collective invasion. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3621.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".