Prognostic significance of SOCS1 and SOCS3 tumor suppressors and oncogenic signaling pathway genes in hepatocellular carcinoma
Bibliographic record
Abstract
BACKGROUND: SOCS1 and SOCS3 genes are considered tumor suppressors in hepatocellular carcinoma (HCC) due to frequent epigenetic repression. Consistent with this notion, mice lacking SOCS1 or SOCS3 show increased susceptibility to diethylnitrosamine (DEN)-induced HCC. As SOCS1 and SOCS3 are important regulators of cytokine and growth factor signaling, their loss could activate oncogenic signaling pathways. Therefore, we examined the correlation between SOCS1/SOCS3 and key oncogenic signaling pathway genes as well as their prognostic significance in HCC. METHODS: The Cancer Genome Atlas dataset on HCC comprising clinical and transcriptomic data was retrieved from the cBioportal platform. The correlation between the expression of SOCS1 or SOCS3 and oncogenic pathway genes was evaluated using the GraphPad PRISM software. The inversely correlated genes were assessed for their impact on patient survival using the UALCAN platform and their expression quantified in the regenerating livers and DEN-induced HCC tissues of mice lacking Socs1 or Socs3. Finally, the Cox proportional hazards model was used to evaluate the predictive potential of SOCS1 and SOCS3 when combined with the genes of select oncogenic signaling pathways. RESULTS: SOCS1 expression was comparable between HCC and adjacent normal tissues, yet higher SOCS1 expression predicted favorable prognosis. In contrast, SOCS3 expression was significantly low in HCC, yet it lacked predictive potential. The correlation between SOCS1 or SOCS3 expression and key genes of the cell cycle, receptor tyrosine kinase, growth factor and MAPK signaling pathways were mostly positive than negative. Among the negatively correlated genes, only a few showed elevated expression in HCC and predicted survival. Many PI3K pathway genes showed mutual exclusivity with SOCS1 and/or SOCS3 and displayed independent predictive ability. Among genes that negatively correlated with SOCS1 and/or SOCS3, only CDK2 and AURKA showed corresponding modulations in the regenerating livers and DEN-induced tumors of hepatocyte-specific Socs1 or Socs3 deficient mice and predicted patient survival. The Cox proportional hazards model identified the combinations of SOCS1 or SOCS3 with CXCL8 and DAB2 as highly predictive. CONCLUSIONS: SOCS1 expression in HCC has an independent prognostic value whereas SOCS3 expression does not. The predictive potential of SOCS1 expression is increased when combined with other oncogenic signaling pathway genes.
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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 | 0.001 | 0.001 |
| 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 | 0.000 | 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 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".