19P - Stratified control study on neuroendocrine differentiation and potential clinical markers in patients with limited-stage small-cell lung cancer

Background

SCLC is highly heterogeneous and can be divided into NE (Neuroendocrine)-high and NE-low groups according to 50 genes on transcriptomic level, harboring different immune microenvironments and potential immunotherapy reactivity. However, this is still far from clinical application since the current three classic NE markers (ChrA, Syn,and CD56) are not very satisfactory either for specificity or sensitivity. It is necessary to explore novel NE markers, that are both close to NE gene subtyping and feasible for clinicopathological use.

Methods

Quantitative detection of NE mRNA genes by Nanostring nCounter as well as INSM1 protein by immunohistochemistry was performed simultaneously on 48 whole slides as testing group. Spearman correlation was applied for consistency analysis of 50 genes and INSM1 protein expression, and the best cut-off for INSM1 expression was validated on 247 tissue microarrays for comparison of the 3 traditional NE protein markers for specificity and sensibility as well as prognostic significance.

Results

In 48 cases, quantitative detection revealed 83.3% for NE-high and 16.7% for NE-low, while for INSM1 protein grouping, it was 79.2% (H-score>100) for NE(INSM1)-high and 20.8% (H-score<=100) for NE(INSM1)-low. NE subtypes defined by INSM1 protein and NE genes had significant consistency in terms of proportion (p=0.026). In addition, 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 subtypes have a tendency to poor prognosis. In 247 cases of validation exploration, INSM1 expression was positively correlated with 3 classical markers, moreover, 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 OS rates in the NE(INSM1)-high group were slightly lower than those in the NE(INSM1)-low group.

Conclusions

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

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.