Gezelius Emelie, Bendahl Pär-Ola, Gallo Widet, de Oliveira Kelin Gonçalves, Ek Lars, Bergman Bengt, Sundberg Jan, Melander Olle, Belting Mattias
Department of Clinical Sciences, Lund, Division of Oncology, Lund University, Barngatan 4, SE-221 85 Lund, Sweden.
Department of Respiratory Medicine, Lund University Hospital, Entrégatan 7, SE-221 85 Lund, Sweden.
Cancers (Basel). 2022 Mar 3;14(5):1307. doi: 10.3390/cancers14051307.
Cardiovascular comorbidity is common in small cell lung cancer (SCLC) and may significantly affect treatment tolerability and patient outcome. Still, there are no established biomarkers for objective and dynamic assessment as a tool for improved treatment decisions. We have investigated circulating levels of midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial-natriuretic peptide (MR-proANP), copeptin (surrogate for vasopressin) and suppression-of-tumorigenicity-2 (ST2), all known to correlate with various aspects of cardiovascular function, in a SCLC cohort (N = 252) from a randomized, controlled trial (RASTEN). For all measured biomarkers, protein levels were inversely associated with survival, particularly with ST2 and MR-proADM, where the top versus bottom quartile was associated with an adjusted hazard ratio of 2.40 (95% CI 1.44−3.98; p = 0.001) and 2.18 (95% CI 1.35−3.51; p = 0.001), respectively, in the entire cohort, and 3.43 (95% CI 1.73−6.79; p < 0.001) and 3.49 (95% CI 1.84−6.60; p < 0.001), respectively, in extensive disease patients. A high combined score of MR-proADM and ST2 was associated with a significantly reduced median OS of 7.0 months vs. 14.9 months for patients with a low combined score. We conclude that the cardiovascular biomarkers MR-proADM and ST2 strongly correlate with survival in SCLC, warranting prospective studies on the clinical utility of MR-proADM and ST2 for improved, individualized treatment decisions.
心血管合并症在小细胞肺癌（SCLC）中很常见，可能会显著影响治疗耐受性和患者预后。然而，目前尚无用于客观动态评估的既定生物标志物作为改善治疗决策的工具。我们在一项来自随机对照试验（RASTEN）的SCLC队列（N = 252）中，研究了中段前肾上腺髓质素（MR-proADM）、中段前心钠素（MR-proANP）、 copeptin（血管加压素替代物）和抑瘤素2（ST2）的循环水平，所有这些都已知与心血管功能的各个方面相关。对于所有测量的生物标志物，蛋白质水平与生存率呈负相关，特别是与ST2和MR-proADM，在整个队列中，最高四分位数与最低四分位数相比，调整后的风险比分别为2.40（95%CI 1.44−3.98；p = 0.001）和2.18（95%CI 1.35−3.51；p = 0.001），在广泛期疾病患者中分别为3.43（95%CI 1.73−6.79；p < 0.001）和3.49（95%CI 1.84−6.60；p < 0.001）。MR-proADM和ST2的高综合评分与低综合评分患者相比，中位总生存期显著缩短，分别为7.0个月和14.9个月。我们得出结论，心血管生物标志物MR-proADM和ST2与SCLC的生存率密切相关，有必要对MR-proADM和ST2的临床效用进行前瞻性研究，以改善个体化治疗决策。
