142P - Role and impact of hypoxia-inducible factor 1-alpha on survival rates in pancreatic cancer: A systematic review and meta-analysis

Background

Pancreatic cancer (PC) remains a major health concern due to its dismal prognosis and high mortality rates. Hypoxia-inducible factor 1-alpha (HIF-1α) is implicated in promoting tumor growth, angiogenesis, and metabolic changes under hypoxic conditions. However, an all-inclusive understanding of HIF-1α's precise role and clinical impact on PC is yet to be ascertained. This study aims to study the influence of HIF-1α on PC. Specifically, the goal is to assess differences in overall survival (OS) and OS in the context of metastasis between PC patients with high and low expression of HIF-1α.

Methods

We comprehensively searched PubMed, Embase, and the Cochrane Library databases for relevant research articles published until December 2022. Studies eligible for inclusion compared clinical outcomes in PC patients expressing high and low levels of HIF-1α. Primary outcomes of interest were OS and OS in patients with metastasis, computed using the hazard ratio (HR). The R software (version 4.0.3) with metafor and meta packages was used for all statistical analyses, utilizing random-effects models.

Results

Our meta-analysis encompassed 16 studies, representing a cohort of 1,080 PC patients, including 566 with high HIF-1α expression and 514 with low HIF-1α expression. The pooled HR for OS was 1.86 (95% CI: 1.64-2.12, P<0.01, I2=0%), indicating significantly lower survival rates among patients expressing high HIF-1α. More crucially, the pooled HR for OS in patients with metastasis was 2.09 (95% CI: 1.67-2.64, P<0.01, I2=0%), suggesting an even poorer survival outcome in metastatic PC patients with high HIF-1α expression.

Conclusions

Our findings highlight the considerable prognostic role of HIF-1α in PC, particularly elucidating its fundamental role in disease progression and prognosis, especially in the context of metastasis. These insights could stimulate the development of innovative therapeutic strategies that target HIF-1α, with potential implications for enhancing survival rates in PC patients. Further studies should validate these findings in larger, prospective cohorts and further investigate the specific mechanisms through which HIF-1α exacerbates PC progression, particularly in metastatic cases.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.