Penn State Cancer Institute, Hershey, PA, United States of America.
Department of Medicine, Milton S. Hershey Medical Center, Hershey, PA, United States of America.
PLoS One. 2021 Dec 2;16(12):e0260988. doi: 10.1371/journal.pone.0260988. eCollection 2021.
Blood-based biomarkers including systemic inflammation (SI) indicators or circulating factors (cytokines, chemokines, or growth factors) are associated with a poor prognosis for lung cancer patients. Collectively these biomarkers can predict the immune state of a patient. We wanted to define and compare the immune states of small cell and non-small cell lung cancer patients, in the hopes that the information gained could lead to overall improvements in patient care and outcomes. Specimens and data from 235 patients was utilized, 49 surgically resected non-small cell lung cancer (NSCLC) patients with no evidence of disease (DF), 135 advanced non-small cell lung cancer (NSCLC), 51 small cell lung cancer (SCLC). SI markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI) were determined from blood counts. Forty-seven plasma cytokines were measured using a multiplex bead-based assay. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox Proportional Hazards models. NSCLC patients had significantly high levels of SI markers than SCLC and DF patients, while NLR, PLR and SII were also higher in SCLC than DF patients. SI optimized marker values to differentiate SI value were; 6.04 (NLR), 320 (PLR), 1615 (SII), and 7.3 (SIRI). Elevated levels NLR (p<0.001), PLR (p<0.001), and SII (p = 0.018) were associated with a worse PFS and OS in NSCLC, while none of the markers were associated with PFS in SCLC patients. NSCLC patients with a poor outcome displayed heterogeneous immune states relative to systemic inflammation and circulating IL-6 markers. These groups could be distinguished based on the cytokines IL-8, TNFα, and IL-27. We identified heterogeneity of immune states in SCLC and NSCLC patients and in NSCLC patients with the poorest prognosis. This heterogeneity could be exploited to improve outcomes for these patients.
血液生物标志物包括全身炎症（SI）指标或循环因子（细胞因子、趋化因子或生长因子）与肺癌患者的预后不良相关。这些生物标志物共同可以预测患者的免疫状态。我们希望定义和比较小细胞肺癌和非小细胞肺癌患者的免疫状态，希望获得的信息能够整体改善患者的治疗效果和预后。利用了 235 名患者的标本和数据，其中 49 名手术切除的非小细胞肺癌（NSCLC）患者无疾病证据（DF），135 名晚期非小细胞肺癌（NSCLC）患者，51 名小细胞肺癌（SCLC）患者。通过血细胞计数确定全身炎症标志物中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）、全身炎症指数（SII）和全身炎症反应指数（SIRI）。使用基于多重珠的测定法测量了 47 种血浆细胞因子。使用 Kaplan-Meier 和 Cox 比例风险模型评估无进展生存期（PFS）和总生存期（OS）。与 SCLC 和 DF 患者相比，NSCLC 患者的全身炎症标志物水平显著升高，而 NLR、PLR 和 SII 在 SCLC 患者中也高于 DF 患者。区分 SI 值的最佳 SI 优化标志物值为; 6.04（NLR）、320（PLR）、1615（SII）和 7.3（SIRI）。NLR（p<0.001）、PLR（p<0.001）和 SII（p = 0.018）升高与 NSCLC 患者的 PFS 和 OS 较差相关，而 SCLC 患者的标志物均与 PFS 无关。预后不良的 NSCLC 患者的全身炎症和循环 IL-6 标志物显示出异质性的免疫状态。这些组可以根据细胞因子 IL-8、TNFα 和 IL-27 来区分。我们在小细胞肺癌和非小细胞肺癌患者以及预后最差的非小细胞肺癌患者中发现了免疫状态的异质性。这种异质性可以被利用来改善这些患者的治疗效果。
