2025P - Stratified control study of neuroendocrine differentiation and potential clinicopathologic markers

Background

SCLC is highly heterogeneous which was divided into NE (Neuroendocrine)-high and NE-low groups according to 50 genes on transcriptomic level, harboring different immune microenvironments and potential immunotherapy reactivity. It is necessary to explore novel NE markers, that both are close to NE gene subtyping and feasible for clinicopathological use. Here, we conducted a parallel comparative study at mRNA and protein levels for exploring the potential of INSM1 as a substitute marker for NE subtyping.

Methods

Two hundred and forty-seven surgical specimens were collected. Quantitative detection of NE genes by Nanostring nCounter as well as INSM1 protein by IHC was performed simultaneously on 48 whole slides as testing group. Spearman correlation was applied for consistency analysis, and the best cut-off for INSM1 expression was validated on 247 tissue microarrays for comparison of the three traditional NE protein markers for specificity and sensibility as well as prognostic significance.

Results

In 48 testing cases, quantitative detection revealed 83.3% (40/48) for NE-high and 16.7% (8/48) for NE-low, while for protein grouping, it was 79.2% (38/48, H-score>100) for NE(INSM1)-high and 20.8% (10/48, H-score<=100) for NE(INSM1)-low. NE classification defined by INSM1 protein and NE genes had significant consistency in terms of proportion (p=0.026). NE groups also had consistent clinical characteristics and prognostic trend in the two levels. Patients with NE-high and NE(INSM1)-high tended to be in the advanced stage. Patients with NE-high and NE(INSM1)-high have a tendency of poor prognosis. In 247 cases of validation exploration, INSM1 expression was positively correlated with three classical markers, more importantly, in triple negative cases, INSM1 showed a favorable positive rate (1.5%, 3/198). In addition, NE(INSM1)-high patients showed more bronchial invasion and tumor thrombosis than that of NE(INSM1)-low ones (p<0.05), and the 1-, 3-, and 5-year OS rates in the NE(INSM1)-high group were slightly lower than those in the NE(INSM1)-low group.

Conclusions

INSM1 has great potential being a marker of NE differentiation and subgrouping, also shows a certain correlation with prognosis and some clinicopathological factors.

Clinical trial identification

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.