Guo Chao, Deng Jiaqin, Wen Tianhua, Li Jinzhou, Zeng Peilin, Liang Chao
Department of Plastic Surgery, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, 514000, People's Republic of China.
Department of Thyroid Surgery, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, Meizhou, 514000, China.
Discov Oncol. 2025 Mar 19;16(1):361. doi: 10.1007/s12672-025-02122-0.
Platelets (PLT) play a crucial role in tumor progression, including tumor growth, metastasis, and immune evasion. However, the relationship between PLT count and specific skin cancer subtypes, particularly melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC), remains poorly understood. Clarifying this association could identify potential biomarkers and therapeutic targets for personalized treatments.
We applied bidirectional Mendelian randomization (MR) to investigate the causal relationship between PLT count and skin cancer risk, focusing on MSC and NMSC. Genetic variants associated with PLT and skin cancer served as instrumental variables for causal inference. Nine MR analysis methods, with inverse-variance weighted (IVW) as the primary method, were used to assess robustness, heterogeneity, and pleiotropy.
Forward MR analysis showed no significant relationship between PLT count and overall skin cancer or NMSC. However, elevated PLT was linked to an 18.6% increased risk of MSC. Reverse MR analysis revealed that skin cancer, particularly NMSC, negatively affected PLT count, while MSC was associated with a positive influence on PLT levels. No significant heterogeneity or pleiotropy was detected.
Our findings reveal a bidirectional, subtype-specific relationship between PLT and skin cancer. Elevated PLT levels specifically increase the risk of MSC, while MSC influences PLT count positively. In contrast, NMSC is associated with lower PLT levels. These results suggest that PLT could serve as both a prognostic marker and a potential therapeutic target, particularly for MSC. Further research is needed to explore the molecular mechanisms underlying these associations and to investigate the role of PLT in overcoming tumor resistance to therapies.
血小板（PLT）在肿瘤进展中发挥着关键作用，包括肿瘤生长、转移和免疫逃逸。然而，血小板计数与特定皮肤癌亚型，特别是黑色素瘤皮肤癌（MSC）和非黑色素瘤皮肤癌（NMSC）之间的关系仍知之甚少。阐明这种关联可以确定个性化治疗的潜在生物标志物和治疗靶点。
我们应用双向孟德尔随机化（MR）来研究血小板计数与皮肤癌风险之间的因果关系，重点关注MSC和NMSC。与血小板和皮肤癌相关的基因变异作为因果推断的工具变量。使用九种MR分析方法，以逆方差加权（IVW）作为主要方法，来评估稳健性、异质性和多效性。
正向MR分析显示血小板计数与总体皮肤癌或NMSC之间无显著关系。然而，血小板升高与MSC风险增加18.6%相关。反向MR分析显示，皮肤癌，特别是NMSC，对血小板计数有负面影响，而MSC与血小板水平的正向影响相关。未检测到显著的异质性或多效性。
我们的研究结果揭示了血小板与皮肤癌之间的双向、亚型特异性关系。血小板水平升高特别增加了MSC的风险，而MSC对血小板计数有正向影响。相比之下，NMSC与较低的血小板水平相关。这些结果表明，血小板既可以作为预后标志物，也可以作为潜在的治疗靶点，特别是对于MSC。需要进一步研究来探索这些关联背后的分子机制，并研究血小板在克服肿瘤对治疗的抗性中的作用。
