目的:本研究的目的是分析血清指标与高通量药物筛选(HDS)结果之间的关系,旨在实现对肝细胞癌(HCC)的特异性治疗。
方法:本研究招募了2019年12月至2021年12月在重庆医科大学附属第一医院肝胆外科中心行手术切除的肝癌患者。在手术期间从患者获得HCC组织并进行体外细胞培养,然后对培养的组织样品进行HDS测试。我们使用Spearman的相关分析来检验抗肝癌药物的药物敏感性结果之间的关系。其他抗肿瘤药物,和血清学指标,中性粒细胞淋巴细胞比率(NLR),血小板淋巴细胞比率(PLR),全身免疫炎症指数(SII),全身炎症反应指数(SIRI),预后营养指数(PNI),和淋巴细胞单核细胞比率(LMR)。当P<0.05和|r|>0.40时,认为存在显着相关性。此外,进行线性回归分析以阐明血清学指标与药物敏感性之间的关系,P<0.05和R²≥0.50表明有显著性结果。
结果:在这项研究中,对82例接受肝切除术并完成体外细胞培养和HDS测试的HCC患者进行了评估。使用Spearman与显著性阈值P<0.05和|r|>0.40的相关性,我们确定了血清学指标与特定药物方案之间的显著关联:NLR与5-氟尿嘧啶相关,5-氟尿嘧啶+亚叶酸钙(FOLFOX4),和卡培他滨+顺铂(XP);PLR与FOLFOX4;SII与XP,FOLFOX4,多柔比星+奥沙利铂(ADM+L-OHP);和具有XP和FOLFOX4的SIRI。在PNI或LMR与任何药物抑制率之间未发现相关性。使用线性回归分析的综合评价-包括性别等变量,年龄,乙型肝炎病毒和肝硬化状态,病变的大小和数量,甲胎蛋白,总胆红素,白蛋白,丙氨酸氨基转移酶,天冬氨酸转氨酶,和凝血酶原时间,与NLR一起,PLR,SII,和SIRI是针对药物治疗方案进行的。这项分析表明,NLR,SII,和SIRI是FOLFOX4抑制率的重要预测因子,而NLR能有效预测XP的抑制率。然而,分子靶向药物之间没有建立显著的联系,其他抗肿瘤药物,和血清学指标。
结论:NLR,SII,和SIRI与FOLFOX4相关,NLR值越高,SII,和SIRI,FOLFOX的体外抑制作用越高。此外,NLR与XP相关,NLR的值越高,XP的体外抑制作用越高。
OBJECTIVE: The purpose of this study was to analyze the relationship between serum indicators and high-throughput drug screening (HDS) results, aiming to achieve specific therapy for hepatocellular carcinoma (HCC).
METHODS: This study recruited patients with HCC who underwent surgical resection at the Hepatobiliary Surgery Center of the First Affiliated Hospital of Chongqing Medical University from December 2019 to December 2021. HCC tissues were obtained from patients during surgery and subjected to in vitro cell culture, and then HDS testing was performed on the cultured tissue samples. We used Spearman\'s correlation analysis to examine the relationships between drug sensitivity results for anti-hepatocellular carcinoma drugs, other antitumor drugs, and serological indicators, the Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammatory Index (SII), Systemic Inflammatory Response Index (SIRI), Prognostic Nutritional Index (PNI), and Lymphocyte Monocyte Ratio (LMR). A significant correlation was considered when P<0.05 and |r|>0.40. Furthermore, linear regression analysis was conducted to elucidate the relationship between serological indicators and drug susceptibility, with significant results indicated by P<0.05 and R²≥0.50.
RESULTS: In this study, 82 patients with HCC who had undergone hepatectomy and completed in vitro cell culture and HDS testing were evaluated. Using Spearman\'s correlation with a significance threshold of P<0.05 and |r|>0.40, we identified significant associations between serological indicators and specific drug regimens: NLR correlated with 5-Fluorouracil, 5- Fluorouracil+Calcium folinate (FOLFOX4), and Capecitabine + Cisplatin (XP); PLR with FOLFOX4; SII with XP, FOLFOX4, Doxorubicin + Oxaliplatin (ADM+L-OHP); and SIRI with XP and FOLFOX4. No correlations were found between PNI or LMR and any drug inhibition rates. A comprehensive evaluation using linear regression analysis-which included variables such as sex, age, hepatitis B virus and liver cirrhosis status, size and number of lesions, alphafetoprotein, total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, and prothrombin time, alongside NLR, PLR, SII, and SIRI was conducted in relation to drug regimens. This analysis revealed that NLR, SII, and SIRI are significant predictors of FOLFOX4 inhibition rate, while NLR predicts the inhibition rate of XP effectively. However, no significant links were established between molecular targeted drugs, other antitumor drugs, and serological indicators.
CONCLUSIONS: NLR, SII, and SIRI were correlated with FOLFOX4, and the higher the values of NLR, SII, and SIRI, the higher the in vitro inhibition of FOLFOX. Also, NLR was correlated with XP, and the higher the value of NLR, the higher the in vitro inhibition of XP.