Scholarlink

Background <p><i>KRAS</i>‑mutant non‑small cell lung cancer (NSCLC) is heterogeneous, but the subtype‑specific profiles of systemic cytokines and their impact on immunotherapy outcomes remain unclear.</p> Methods <p>This retrospective study included 139 patients with <i>KRAS</i>‑mutant NSCLC stratified into G12C (44.6%), G12D (21.6%), and other G12 variants (G12V/A/S/R) (33.8%). Serum levels of seven cytokines (IL‑6, IL‑8, TNF‑α, IL‑10, IL‑17, IL‑1β, IL‑4) were available for 109 patients. Associations with progression‑free survival (PFS) and overall survival (OS) were analyzed using Kaplan‑Meier and Cox regression.</p> Results <p>Distinct cytokine profiles emerged across subtypes: IL‑10 was elevated in G12C, while IL‑17 was higher in G12D. In the overall ICI‑treated cohort (<i>n</i> = 80), elevated IL‑6, IL‑8, and TNF‑α were associated with worse PFS and OS in univariable analyses. After multivariable adjustment, only IL‑6 remained an independent unfavorable prognostic factor for PFS (adjusted HR = 2.66, <i>p</i> = 0.042). For OS, all three cytokines remained significant after limited adjustment (IL‑6&#xa0;HR = 2.67, <i>p</i> = 0.050; IL‑8&#xa0;HR = 5.00, <i>p</i> = 0.049; TNF‑α HR = 2.61, <i>p</i> = 0.037), but findings were exploratory due to not adjusted for multiple testing. In first‑line patients (<i>n</i> = 57), only IL‑6 predicted worse PFS (adjusted HR = 5.34, <i>p</i> = 0.002). Subgroup analysis showed that in G12C (<i>n</i> = 38), IL‑6 and TNF‑α were associated with worse PFS/OS, while in G12D (<i>n</i> = 16), IL‑17 showed a significant association with shorter PFS (log‑rank <i>p</i> = 0.037). No cytokine was prognostic in the G12V/A/S/R subgroup.</p> Conclusion <p>These findings suggest that <i>KRAS</i> mutation subtypes may be associated with distinct serum cytokine profiles. IL-6 appeared as a potential subtype-independent negative prognostic factor for PFS, while IL-17 may be relevant in G12D tumors. These observations provide an early rationale for exploring subtype-specific cytokine-targeted strategies, though confirmation in larger prospective cohorts is needed.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Serum cytokine profiles in a real-world cohort of KRAS-Mutant NSCLC and its therapeutic implications for subtype-specific immunotherapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月1日

查看全文
  • Bo Yuan,
  • Yuanyi Zhang,
  • Xiao Li,
  • YuJiao Dong,
  • Xiaopeng An,
  • Tong Jiao,
  • Cai Zhang,
  • Yang Chen,
  • Jie Shi,
  • Shiqi Wu,
  • Shuanying Yang

摘要

Background

KRAS‑mutant non‑small cell lung cancer (NSCLC) is heterogeneous, but the subtype‑specific profiles of systemic cytokines and their impact on immunotherapy outcomes remain unclear.

Methods

This retrospective study included 139 patients with KRAS‑mutant NSCLC stratified into G12C (44.6%), G12D (21.6%), and other G12 variants (G12V/A/S/R) (33.8%). Serum levels of seven cytokines (IL‑6, IL‑8, TNF‑α, IL‑10, IL‑17, IL‑1β, IL‑4) were available for 109 patients. Associations with progression‑free survival (PFS) and overall survival (OS) were analyzed using Kaplan‑Meier and Cox regression.

Results

Distinct cytokine profiles emerged across subtypes: IL‑10 was elevated in G12C, while IL‑17 was higher in G12D. In the overall ICI‑treated cohort (n = 80), elevated IL‑6, IL‑8, and TNF‑α were associated with worse PFS and OS in univariable analyses. After multivariable adjustment, only IL‑6 remained an independent unfavorable prognostic factor for PFS (adjusted HR = 2.66, p = 0.042). For OS, all three cytokines remained significant after limited adjustment (IL‑6 HR = 2.67, p = 0.050; IL‑8 HR = 5.00, p = 0.049; TNF‑α HR = 2.61, p = 0.037), but findings were exploratory due to not adjusted for multiple testing. In first‑line patients (n = 57), only IL‑6 predicted worse PFS (adjusted HR = 5.34, p = 0.002). Subgroup analysis showed that in G12C (n = 38), IL‑6 and TNF‑α were associated with worse PFS/OS, while in G12D (n = 16), IL‑17 showed a significant association with shorter PFS (log‑rank p = 0.037). No cytokine was prognostic in the G12V/A/S/R subgroup.

Conclusion

These findings suggest that KRAS mutation subtypes may be associated with distinct serum cytokine profiles. IL-6 appeared as a potential subtype-independent negative prognostic factor for PFS, while IL-17 may be relevant in G12D tumors. These observations provide an early rationale for exploring subtype-specific cytokine-targeted strategies, though confirmation in larger prospective cohorts is needed.