Abstract 720P
Background
Interleukins (IL) as part of the tumor microenvironment (TME) play a key role in Lung cancer development and progression. Attaining knowledge of these interleukins may offer new insights into cancer prognosis and help identify newer therapeutic targets. Our study aims to find an association between IL gene expression and patient outcomes.
Methods
This prospective study included 100 treatment-naive patients with stage IV NSCLC and 10 apparently healthy individuals. Total RNA was extracted from peripheral blood by using an RNeasy kit. Following this, cDNA was synthesized and gene expression of 6 interleukins (IL1β, IL6, IL8, IL10, TNFα, and TLR4) was assessed by SYBR green qPCR and MyGo Pro PCR software. The 2ˆ-ΔΔCt technique was used to calculate the fold change in gene expression, with GAPDH serving as the housekeeping gene (HKG).
Results
The cohort of 100 patients was divided into low and high gene expressers based on IL cutoff values. mPFS observed for different ILs (low vs. high): IL1β (8 vs. 6 months), IL6 (11 vs. 6 months), IL8 (11 vs. 7 months), IL10 (8 vs. 6 months), TNFα (8 vs. 7 months), and TLR4 (8 vs. 7 months). Patients with driver mutations had mPFS of 24 months compared to 5 months for those without. Among driver mutation-positive patients, high expression of IL1β, IL10, and TNFα corresponded with lower mPFS (6, 6 & 7 months respectively). Table: 720P
| IL gene expression (n=100) <1: low expresser >1: high expresser | Driver status | mPFS (mts) | Overall mPFS | P value | |
| IL1 β | <1 (n=88) | neg vs. pos | 5 vs. 24 | 8mts | 0.000 |
| >1 (n=12) | neg vs. pos | 6 vs. 7 | 6mts | 0.190 | |
| IL6 | <1 (n=58) | neg vs. pos | 5 vs. 24 | 11mts | 0.000 |
| >1 (n=42) | neg vs. pos | 5 vs. NR | 6mts | 0.005 | |
| IL8 | <1 (n=65) | neg vs. pos | 5 vs. 24 | 11mts | 0.000 |
| >1 (n=35) | neg vs. pos | 6 vs. 12 | 7mts | 0.009 | |
| IL10 | <1 (n=88) | neg vs. pos | 5 vs. 24 | 8mts | 0.000 |
| >1 (n=12) | neg vs. pos | 6 vs. 7 | 6mts | 0.412 | |
| TNFα | <1 (n=79) | neg vs. pos | 5 vs. 24 | 8mts | 0.000 |
| >1 (n=21) | neg vs. pos | 6 vs. 7 | 7mts | 0.367 | |
| TLR4 | <1 (n=64) | neg vs. pos | 5 vs. 24 | 8mts | 0.000 |
| >1 (n=36) | neg vs. pos | 6 vs. 12 | 7mts | 0.009 | |
Conclusions
High expression of IL1β, IL10, and TNFα in driver mutation-positive NSCLC patients may diminish the benefits of targeted therapy, highlighting the prognostic significance of interleukin gene expression levels in lung cancer.
Clinical trial identification
CTRI/2023/09/073817 H.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.