Tumor B7-H3 (CD276) expression and smoking history in relation to lung adenocarcinoma prognosis. (January 2017)

• Record Type: Journal Article
• Authors: Inamura, Kentaro; Yokouchi, Yusuke; Kobayashi, Maki; Sakakibara, Rie; Ninomiya, Hironori; Subat, Sophia; Nagano, Hiroko; Nomura, Kimie; Okumura, Sakae; Shibutani, Tomoko; Ishikawa, Yuichi
• Is Part Of: Lung cancer. Volume 103(2017)
• Page Start: 44
• Page End: 51
• Publication Date: 2017-01
• Subjects: CI confidence interval -- HR hazard ratio -- OR odds ratio -- PD-1 programmed death-1 -- PD-L1 programmed death-ligand 1 -- p-stage pathological stage -- SI smoking index; B7-H3 -- Immune checkpoint -- Immunotherapy -- Lung cancer -- Smoking -- Prognostic interaction; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.11.013
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: We evaluated tumor B7-H3 expression by IHC in 270 lung adenocarcinomas. We demonstrated a significant prognostic interaction of B7-H3 with smoking history. In smoking patients, high B7-H3 expression was associated with decreased survival. In non-smoking patients, high B7-H3 expression was not associated with survival. High B7-H3 expression was associated with EGFR wild-type and smoking patients. Abstract: Objectives: Compared with non-smoking counterparts, smoking-associated lung cancers have a higher mutational load, resulting in the creation of more tumor neoantigens and increased immunogenicity. B7-H3 (also known as CD276) belongs to a family of immune modulators that includes PD-1 and PD-L1 (also known as B7-H1 or CD274). Considering the evidence that PD-L1 inhibitors have been shown to be more effective against lung cancer in smokers, we herein examined the prognostic interaction of tumor B7-H3 expression level with smoking history in lung adenocarcinoma patients. Materials and methods: Using tissue microarrays comprising 270 consecutive cases of lung adenocarcinoma, we evaluated tumor B7-H3 expression by immunohistochemistry. We examined the prognostic association between B7-H3 expression levels and smoking history, using Cox proportional hazards regression analysis and the log-rank test. Additionally, we used logistic regression analysis to examine the correlations between B7-H3 expression levels and clinicopathological/molecular features of lung adenocarcinoma. Results: The association of B7-H3 expression with survival differed by smoking history ( P interaction = 0.014); high B7-H3 expression was associated with decreased lung cancer-specific survival in moderate/heavy-smoking patients (smoking index [SI] ≥ 400) (hazard ratio [HR] = 3.07, 95% confidence interval [CI] = 1.74–5.49, P = 0.0001; log-rank: P < 0.0001), but not in non/light-smoking patients (SI < 400) (HR = 1.14, 95% CI = 0.63–1.96, P = 0.64; log-rank: P = 0.64). Interestingly, in moderate/heavy-smoking patients, high B7-H3 expression was associated with decreased survival in stage I cancer (log-rank; P = 0.0005), whereas it showed no significant difference of survival in stage II–IV cancer ( P = 0.37). High B7-H3 expression was associated with smokers (univariable odds ratio [OR] = 2.63, 95% CI = 1.51–4.65; P = 0.0005) and independently associated with EGFR wild-type status (multivariable OR = 2.80, 95% CI = 1.38–5.84; P = 0.0042). Conclusions: We demonstrated that the prognostic association of B7-H3 expression indeed differed according to smoking history. Our study also showed the significant association of high B7-H3 expression with EGFR wild-type and smoking patients, indicating the potential effectiveness of anti-B7-H3 therapy for EGFR wild-type or smokers' lung adenocarcinoma.