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Background <p>Ovarian cancer (OC) is often diagnosed at an advanced stage when prognosis is poor. We aimed to identify blood plasma proteins predictive of OC risk.</p> Methods <p>We conducted proteome-wide Mendelian randomisation (MR) analyses using summary-level protein quantitative trait locus data covering 2337 plasma proteins, and genome-wide association data on OC and its subtypes (up to 25,509 cases) from the Ovarian Cancer Association Consortium. Wald ratio or inverse-variance weighted MR analysis was used as the primary method, depending on the number of instruments. We evaluated pleiotropy using MR-Egger intercept test and leave-one-out analysis.</p> Results <p>From 2337 plasma proteins, 12 were associated (<i>p</i> &lt; 7.4 × 10<sup>−5</sup>) with OC or its subtypes. Robust evidence linked follitropin subunit beta (FSHB) with endometrioid OC (per SD higher, OR 2.41, 95% CI 1.56, 3.71). Associations for the other 11 proteins could be explained by pleiotropy from <i>ABO</i> or <i>MAPT-AS1</i> loci. We identified 12 suggestive associations with OC or its subtypes at nominal threshold (<i>p</i> &lt; 0.05), involving 11 plasma proteins, with no evidence of pleiotropy from leave-one-out and MR-Egger intercept tests (<i>P</i><sub>intercept</sub> &gt; 0.17). Potential drug targets were identified for follitropin receptor and eight other proteins.</p> Conclusion <p>Our study suggests FSHB and 11 additional plasma proteins as of potential interest in OC (or subtypes) prognosis, mostly representing potentially druggable targets.</p> <p></p>

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Protein markers of ovarian cancer and its subtypes: insights from proteome-wide Mendelian randomisation analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月28日

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  • Anwar Mulugeta,
  • David Stacey,
  • Amanda L. Lumsden,
  • Iqbal Madakkatel,
  • S. Hong Lee,
  • Johanna Mäenpää,
  • Martin K. Oehler,
  • Elina Hyppönen

摘要

Background

Ovarian cancer (OC) is often diagnosed at an advanced stage when prognosis is poor. We aimed to identify blood plasma proteins predictive of OC risk.

Methods

We conducted proteome-wide Mendelian randomisation (MR) analyses using summary-level protein quantitative trait locus data covering 2337 plasma proteins, and genome-wide association data on OC and its subtypes (up to 25,509 cases) from the Ovarian Cancer Association Consortium. Wald ratio or inverse-variance weighted MR analysis was used as the primary method, depending on the number of instruments. We evaluated pleiotropy using MR-Egger intercept test and leave-one-out analysis.

Results

From 2337 plasma proteins, 12 were associated (p < 7.4 × 10−5) with OC or its subtypes. Robust evidence linked follitropin subunit beta (FSHB) with endometrioid OC (per SD higher, OR 2.41, 95% CI 1.56, 3.71). Associations for the other 11 proteins could be explained by pleiotropy from ABO or MAPT-AS1 loci. We identified 12 suggestive associations with OC or its subtypes at nominal threshold (p < 0.05), involving 11 plasma proteins, with no evidence of pleiotropy from leave-one-out and MR-Egger intercept tests (Pintercept > 0.17). Potential drug targets were identified for follitropin receptor and eight other proteins.

Conclusion

Our study suggests FSHB and 11 additional plasma proteins as of potential interest in OC (or subtypes) prognosis, mostly representing potentially druggable targets.