Identification of serum inflammatory markers as classifiers of lung cancer mortality for stage I adenocarcinoma

Abstract

BackgroundLung cancer is the leading cause of cancer-related mortality worldwide. Low-dose CT (LDCT) imaging is now recommended to screen high-risk lung cancer individuals in the USA. LDCT has resulted in increased detection of stage I lung cancer for which the current standard of care is surgery alone. However, approximately 30% of these patients develop recurrence and therefore are in need of further treatment upon diagnosis. This study aims to explore blood-based inflammatory biomarkers to identify patients at high-risk of mortality for which additional treatment modalities can be offered at time of diagnosis.Patients and MethodsRecent work on a small panel of circulating cytokines identified elevated levels of IL-6, a pro-inflammatory cytokine, as an indicator of poor survival for lung cancer patients. To reflect the broader role of inflammation in lung cancer, we examined a large panel of 33 inflammatory proteins in the sera of 129 lung cancer patients selected from the National Cancer Institute-Maryland case-control study. To reduce heterogeneity, we specifically focused our study on stage I lung adenocarcinoma patients.ResultsWe replicated the previous observations that IL-6 is associated with prognosis of lung cancer and extended its utility to prognosis in this highly-selected population of stage I lung adenocarcinoma patients. In addition, we developed a multi-marker, combined prognostic classifier that includes the pro-inflammatory Th-17 cell effector cytokine, IL-17. Patients with high levels of IL-6 and IL-17A had a significantly adverse survival compared with patients with low levels (P for trend <0.0001). Patients in the high risk group, with high levels of both proteins had a 5-year survival rate of 46% in comparison to 93% for those with low levels of both markers. Furthermore, we validated the same trends for the IL-6 and IL-17A prognostic signature in an independent data set.ConclusionsThe results identified here justify further investigation of this novel, combined cytokine prognostic classifier for the identification of high-risk stage I lung adenocarcinoma patients. This classifier has the much-needed potential to identify patients at high risk of recurrence and thus prospectively identify the subset of patients requiring more aggressive treatment regimens at the time of diagnosis.

Immune Prophets of Lung Cancer: The Prognostic and Predictive Landscape of Cellular and Molecular Immune Markers

“…Other authors emphasized the importance to identify a “combined cytokine prognostic classifier” to detect patients at high risk of recurrence of lung cancer, thus requiring more aggressive treatment regimens at the time of diagnosis [60] , [61] . These authors firstly found that the high combined expression of IL-8 with IL-6 [60] , and secondly of IL-6 with IL-17 [61] , was negative prognostic factors for stage I lung cancer. In addition to interleukins, also chemokines and/or their receptors expression have been correlated with patient survival or progression in lung cancer.…”

Long non-coding RNA SDPR-AS affects the development of non-small cell lung cancer by regulating SDPR through p38 MAPK/ERK signals

“…Lung cancer remains to be a major cause of cancer-relevant mortality globally [1], of which non-small-cell lung cancer (NSCLC) is the main type with an estimated percentage of 85% [2]. NSCLC can be separated into three histologic subtypes, including adenocarcinoma, squamous cell carcinoma, and large-cell lung carcinoma [3].…”

Blood-based tumor biomarkers in lung cancer for detection and treatment

“…Moreover, peripheral blood mononuclear cell gene expression of CCL3, IL8 and IL1β was found to be higher in lung cancer patients compared to the same patients after removal of their tumors, while CXCL10 and IL2Rα were essentially unchanged (93). Finally, there have been some signals of cytokine signature being of prognostic value as shown in an analysis of patients selected from National Cancer Institute-Maryland case-control study, where patients with stage I NSCLC with high levels of proinflammatory cytokines IL-6 and IL-17A had a significantly adverse survival compared with patients with low levels (94). In summary, cytokines as blood-based biomarkers to facilitate early detection and prognostication of early stage lung cancer is an exciting field of discovery which, nevertheless, needs further development and refinement before being used in clinical practice.…”