Abstract A9: Expression of insulin-like growth factor II and of the type 1 receptor gene in esophageal adenocarcinoma
Bibliographic record
Abstract
Abstract A9 Aim To explore potential biological mechanisms underlying the association between obesity and esophageal malignancy, we studied the expression of insulin-like growth factor-II (IGF-II) and of the type 1 receptor (IGF-IR) gene in a well characterized series of patients with primary esophageal adenocarcinoma (EADC) and matched histologically normal esophageal epithelia (NE). Patients and Methods Banked esophageal tissues (EADC and matched NE, obtained with informed consent) were available from a consecutive series of 52 patients who underwent esophageal resection without preoperative chemoradiation therapy. Following extraction of RNA, expression of IGF-II and IGF-IR mRNA was determined using reverse transcription and real time polymerase chain reaction (RT-PCR). The 2-ΔΔCT (Livak) method was used to quantitate tissue expression of IGF-II and IGF-IR mRNA, which was correlated with measured body mass index (BMI), clinicopathological findings, and outcome. Results As expected, significant correlations between tumor stage, differentiation and survival were found for the 49 male and 3 female patients in this series, who ranged in age from 36 to 85 years (median: 60.5 years). A significant association was seen between BMI and IGF-II mRNA expression in NE tissues (rs=0.26, p=0.075). Significantly higher IGF-II mRNA expression was seen in EADC tumors (median 6.45, 95%CI 7.00-13.46) compared to matched NE tissues (median 1.32, 95%CI 1.37-4.31, p<0.01), particularly in poorly differentiated tumors. On multivariate analysis, IGF-II expression was an independent predictor of disease-free survival (p=0.02) and overall survival (p=0.03). Expression levels of IGF-II mRNA correlated significantly with IGF-IR in both EADC (rs=0.47, p<0.01) and NE (rs=0.46, p<0.01). Furthermore, IGF-IR mRNA expression was found to be significantly higher in EADC (median 1.57; 95%CI 1.47-3.86) compared with matched NE (median 0.57; 95%CI 0.50-0.85) (p<0.01), but only in patients with the A variant of the common IGF-IR G3174A polymorphism, which has recently been shown to modulate the obesity risk for EADC. Conclusions These studies further implicate perturbations of the IGF axis in the molecular pathogenesis of human EADC, and suggest a plausible mechanistic basis to explain the association between obesity and risk for malignancy. The significant association between IGF-II expression and survival suggests that IGF-II may be a clinically relevant biomarker for prognosis, or molecular target for novel anti-cancer therapies. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A9.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.001 | 0.000 |
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 teacher head, 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".