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. 2017 Jun 1;8(33):53978-53988.
doi: 10.18632/oncotarget.9765. eCollection 2017 Aug 15.

PD-L1 and c-MET expression and survival in patients with small cell lung cancer

Lulu Miao #  1 , Yunyun Lu #  1 , Yanjun Xu  1 , Gu Zhang  2 , Zhiyu Huang  1 , Lei Gong  1 , Yun Fan  1
Affiliations

PD-L1 and c-MET expression and survival in patients with small cell lung cancer

Lulu Miao et al. Oncotarget. .

Abstract

Background: Blocking the binding between the PD-1 and PD-L1 has been reported to produce antitumor responses. The MET/HGF axis appears to be another signaling pathway frequently altered in small cell lung cancer (SCLC). Our study was aimed to investigate the expression and prognostic roles of PD-L1 and c-MET in SCLC.

Methods: The expression levels of PD-L1 and c-MET were evaluated by immunohistochemical analysis in 83 SCLC specimens. Survival analysis was performed using the Kaplan-Meier method.

Results: Of the SCLC specimens, 51.8% and 25.3% exhibited positivity for PD-L1 and c-MET, respectively. Higher PD-L1 expression in tumor specimens was significantly correlated with a limited disease (LD) stage, normal levels of serum lactate dehydrogenase (LDH) and neuron-specific enolase (NSE). No association was found between the levels of c-MET and PD-L1 expression or between c-MET expression and other clinical characteristics. SCLC patients with PD-L1-positive tumors showed significantly longer overall survival (OS) than patients with PD-L1-negative tumors (17.0 vs 9.0, p=0.018). Conversely, those with positive c-MET expression exhibited a shorter OS trend (12.0 vs 15.0, p=0.186). However, sub-analysis of LD-stage patients revealed longer OS among the c-MET-negative group (25.0 vs 14.0; p=0.011). The OS of patients with positivity for both PD-L1 and c-MET showed no significant difference compared with other patients (p=0.17). According to multivariate analyses, neither PD-L1 nor c-MET immunoreactivity was a prognostic factor.

Conclusion: Expression of PD-L1 was correlated with LD stage and might serve as a prognostic for better OS in SCLC patients. In LD-stage patients, high c-MET expression might be predictive of a poor outcome.

Keywords: PD-L1; c-MET; expression; prognosis; small cell lung cancer.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that have no conflicts of interest.

Figures

Figure 1
Figure 1. Representative patterns of PD-L1 immunostaining in SCLC tumors with negative A
or strong positive B. staining intensity and c-MET immunostaining with negative C. or strong positive D. staining intensity. Original magnification, ×400.
Figure 2
Figure 2. Significant association of PD-L1 staining score with disease stage, LDH level or NSE level
Data are presented as box-and-whisker plots, and p values were determined using the Wilcoxon rank-sum test.
Figure 3
Figure 3. Kaplan–Meier curves of overall survival (OS) in PD-L1-positive vs PD-L1-negative patients
Overall survival of 83 SCLC patients in relation to PD-L1 status.
Figure 4
Figure 4. Kaplan–Meier curves of overall survival (OS) in PD-L1-positive vs PD-L1-negative patients with LD-stage disease
Overall survival of 47 SCLC patients with LD-stage disease in relation to PD-L1 status.
Figure 5
Figure 5. Kaplan–Meier curves of overall survival (OS) in PD-L1-positive vs PD-L1-negative patients with ED-stage disease
Overall survival of 36 SCLC patients with ED-stage disease in relation to PD-L1 status.
Figure 6
Figure 6. Kaplan–Meier curves of overall survival (OS) in MET-positive vs -negative patients
Overall survival of 83 SCLC patients in relation to c-MET status.
Figure 7
Figure 7. Kaplan–Meier curves of overall survival (OS) in MET-positive vs -negative patients with LD-stage disease
Overall survival of 47 SCLC patients with LD-stage disease in relation to c-MET status.
See this image and copyright information in PMC

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