<p>Prevalence of DLL3, CTLA-4 and MSTN Expression in Patients with Small Cell Lung Cancer</p>

Abstract

IntroductionImmune-based and antibody-drug conjugate therapies have shown promise in the treatment of patients with small cell lung cancer (SCLC). However, better predictive biomarkers are needed for selection of the appropriate SCLC patients for these advanced therapies and also for evaluation of the efficacy of these treatments.ObjectiveThe aim of this study was to examine the expression of delta-like protein 3 (DLL3), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), and mesothelin (MSTN) in patients with SCLC and compare them with those patients’ clinical characteristics.MethodsImmunohistochemical analyses of DLL3, CTLA-4 and MSTN expression were performed in 38 samples from patients with SCLC.ResultsWe found that positive expression in patients of the biomarkers was as follows: for DLL3, 100% (38/38), for CTLA-4, 89.5% (36/38) and for MSTN 81.5% (31/38). The median survival time was 17.9 months in the DLL3 high expression group and 23 months in the DLL3 low expression group. Patients with a high expression of DLL3 showed a poorer prognosis than those with a low expression of DLL3 (HR=3.4; 95% CI, 1.34–8.6; p=0.01).ConclusionThe expression of DLL3, CTLA-4 and MSTN was not correlated with patients’ age, sex, smoking status, stage, and tumor metastasis. The fact that there was a higher expression of DLL3, CTLA-4, and MSTN in SCLC suggested that these molecules could be used as predictive biomarkers for SCLC.

Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors

“…In principle, this notion is consistent with the existing literature. Only 9 previous studies have earlier described associations between high MSLN expression and poor prognosis and/or unfavorable tumor phenotype in these tumor types [ 43 , 45 , 46 , 57 , 74 , 96 , 105 , 106 , 107 ], while there were 7 other studies which could not find associations with clinico-pathological parameters [ 5 , 44 , 47 , 58 , 64 , 65 , 92 ]. The concept of MSLN expression not representing a universal parameter of malignancy is also supported by the frequent MSLN expression in various benign tumors, including Brenner tumors of the ovary, as well as Warthin tumors, pleomorphic adenomas, and basal cell adenomas of the salivary glands.…”

<p>The Role of DLLs in Cancer: A Novel Therapeutic Target</p>

“…56 In GI-NEC, SCLC and SCBC, DLL3 shows a cytoplasmic distribution in tumor cells (reported as Golgi apparatus-localized in a single SCLC study 114 ) but how this influences Notch signaling is unknown. 27,28,112,113,[115][116][117] In LLC cells, DLL3 localizes to the cell nuclei, inhibiting Notch signaling at the transcriptional level. Akt signaling is activated by DLL3, which promotes LLC cell survival and reduces cell apoptosis.…”

Potential prognostic value of delta-like protein 3 in small cell lung cancer: a meta-analysis

“…Finally, we were left with 16 eligible studies after screening the full text, among which 6 articles were included in our final analysis ( Fig. 1) [20][21][22][23][24][25]. Ten articles were excluded for the following reasons: seven articles were review researches and commentaries, one article did not report hazard ratios and Kaplan-Meier curves and 2 articles were abstracts and did not report relevant outcomes.…”

“…One interpretation of this result was that DLL3 expression varies between different populations. The American study indicated that the high expression of DLL3 was a marker of good prognosis [21], and there was no significant correlation between DLL3 expression and prognosis in several Japan studies [22,25], while the high expression of DLL3 is a marker of poor prognosis in China studies [20,23]. These results showed that the expression of DLL3 might be different in different populations.…”

“…High DLL3 expression was associated with bad OS and usually expressed in older patients and advanced stage in endometrial cancer [ 27 ]. Xie et al reported that high DLL3 expression predicted a better OS in patients with SCLC [ 21 ], and other studies foreboded that high DLL3 expression was an inferior prognostic marker for SCLC [ 20 , 23 ]. Thus, the results of different studies remained controversial.…”