Deng Jiaqin, Yu Ming, Gu Yihua, Lai Yeqian, Qiu Lihong
Department of Thyroid 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 Clinical Laboratory, Affiliated Hospital of Guangdong Medical University, No. 57 South Renmin Avenue, Xiashan District, Zhanjiang, 524001, People's Republic of China.
Discov Oncol. 2025 Jan 4;16(1):4. doi: 10.1007/s12672-025-01758-2.
Circulating protein level ratios (CPLRs) may play a crucial role in tumor progression and drug resistance by mediating interactions within the tumor microenvironment. This study aims to investigate the causal associations between CPLRs and papillary thyroid cancer (PTC), focusing on their potential implications in drug resistance mechanisms.
Genetic data for 2821 CPLRs were obtained from the GWAS and FinnGen databases. Mendelian randomization (MR) analysis, using inverse variance weighting (IVW) as the primary method, was conducted to explore causality. Sensitivity analyses, including heterogeneity and pleiotropy tests, were performed to ensure the robustness of the results.
Twelve CPLRs were identified as causally associated with PTC. Seven CPLRs, such as REG1A/TFF3 and LAT/SPARC, were associated with reduced PTC risk, potentially reflecting protective mechanisms. In contrast, five CPLRs, including MAD1L1/PSIP1 and CIAPIN1/TYMP, were linked to increased risk, suggesting their role in promoting drug resistance. Reverse MR analysis revealed no significant causal associations, reinforcing the directionality of these findings.
These findings highlight the relevance of CPLRs in the pathogenesis and drug resistance of PTC, providing insights into potential biomarkers and therapeutic targets. Future research could focus on translating these findings into strategies for personalized medicine and targeted treatment.
循环蛋白水平比值（CPLRs）可能通过介导肿瘤微环境中的相互作用在肿瘤进展和耐药性中发挥关键作用。本研究旨在探讨CPLRs与甲状腺乳头状癌（PTC）之间的因果关联，重点关注其在耐药机制中的潜在意义。
从GWAS和FinnGen数据库中获取2821个CPLRs的遗传数据。采用逆方差加权（IVW）作为主要方法进行孟德尔随机化（MR）分析以探究因果关系。进行敏感性分析，包括异质性和多效性检验，以确保结果的稳健性。
确定了12个CPLRs与PTC存在因果关联。7个CPLRs，如REG1A/TFF3和LAT/SPARC，与PTC风险降低相关，可能反映了保护机制。相反，5个CPLRs，包括MAD1L1/PSIP1和CIAPIN1/TYMP，与风险增加有关，表明它们在促进耐药性方面的作用。反向MR分析未发现显著的因果关联，加强了这些发现的方向性。
这些发现突出了CPLRs在PTC发病机制和耐药性中的相关性，为潜在的生物标志物和治疗靶点提供了见解。未来的研究可以专注于将这些发现转化为个性化医疗和靶向治疗策略。
