FAM83B is a novel biomarker for diagnosis and prognosis of lung squamous cell carcinoma

Abstract

Personalized therapy for non‑small cell lung cancer (NSCLC), particularly lung adenocarcinoma, has recently been significantly improved by the discovery of various molecular targets. However, this has not been the case for lung squamous cell carcinoma (SCC). In the present study, we identified the family with sequence similarity 83, member B (FAM83B) as a candidate marker for SCC through a comprehensive gene expression analysis and examined its correlations with various clinicopathological factors. The subjects of this study consisted of 215 patients with NSCLC who underwent complete resection from 2005 to 2011 at the Fukushima Medical University Hospital (Fukushima, Japan). They included 102 patients with adenocarcinoma and 113 with SCC. FAM83B expression was first examined in some of the samples by gene expression analysis and western blotting, and then all clinical specimens were evaluated by immunohistochemistry (IHC). The relationship between the quantitative values for IHC and clinicopathological factors was statistically analyzed. The results showed that FAM83B mRNA expression was significantly higher in SCC than in normal lung or adenocarcinoma (P<0.0001). Immunoblot analysis also confirmed this trend. Specimens containing >10% positive area for FAM83B were judged as 'positive'; 94.3% (107/113) of SCC and 14.7% (15/102) of adenocarcinoma were positive. Patients were divided into two subgroups according to expression (54 high‑expression and 53 low‑expression patients); the high‑expression group was associated with a better disease‑free survival (DFS) rate (P=0.042, log‑rank test). In conclusion, FAM83B may be a reliable diagnostic and prognostic biomarker for SCC. Detailed analyses of FAM83B function in lung cancer are required to understand how its expression is associated with better prognosis in SCC.

Figure 1

The family with sequence similarity 83 member B (FAM83B) expression in lung cancer and adjacent normal tissue. (A) Expression ratios for FAM83B mRNA in clinical samples of adenocarcinoma (Ad), squamous cell carcinoma (SCC), and adjacent normal lung tissues (NC) were extracted from data obtained via a comprehensive gene expression analysis, and plotted. Horizontal bars indicate medians, ^*P<0.0001. (B) FAM83B expression was examined by western blotting of samples from Ad (5 cases), SCC (5 cases), and NC (3 cases). GAPDH protein expression was examined as an internal control. (C) Immunohistochemistry (IHC) of FAM83B in Ad, SCC, and NC. Paraffin sections were stained using an anti-FAM83B antibody, which was detected by DAB staining. Representative images for each tissue are shown. Boxed regions in the left column are magnified and shown in the right column. Note that immunoreactivity for FAM83B was detected in the cytoplasm and near plasma membranes (arrowheads) in SCC, but were hardly detected in Ad and NC. Scale bars, 100 μm.

Figure 1

The family with sequence similarity 83 member B (FAM83B) expression in lung cancer and adjacent normal tissue. (A) Expression ratios for FAM83B mRNA in clinical samples of adenocarcinoma (Ad), squamous cell carcinoma (SCC), and adjacent normal lung tissues (NC) were extracted from data obtained via a comprehensive gene expression analysis, and plotted. Horizontal bars indicate medians, ^*P<0.0001. (B) FAM83B expression was examined by western blotting of samples from Ad (5 cases), SCC (5 cases), and NC (3 cases). GAPDH protein expression was examined as an internal control. (C) Immunohistochemistry (IHC) of FAM83B in Ad, SCC, and NC. Paraffin sections were stained using an anti-FAM83B antibody, which was detected by DAB staining. Representative images for each tissue are shown. Boxed regions in the left column are magnified and shown in the right column. Note that immunoreactivity for FAM83B was detected in the cytoplasm and near plasma membranes (arrowheads) in SCC, but were hardly detected in Ad and NC. Scale bars, 100 μm.

Figure 1

The family with sequence similarity 83 member B (FAM83B) expression in lung cancer and adjacent normal tissue. (A) Expression ratios for FAM83B mRNA in clinical samples of adenocarcinoma (Ad), squamous cell carcinoma (SCC), and adjacent normal lung tissues (NC) were extracted from data obtained via a comprehensive gene expression analysis, and plotted. Horizontal bars indicate medians, ^*P<0.0001. (B) FAM83B expression was examined by western blotting of samples from Ad (5 cases), SCC (5 cases), and NC (3 cases). GAPDH protein expression was examined as an internal control. (C) Immunohistochemistry (IHC) of FAM83B in Ad, SCC, and NC. Paraffin sections were stained using an anti-FAM83B antibody, which was detected by DAB staining. Representative images for each tissue are shown. Boxed regions in the left column are magnified and shown in the right column. Note that immunoreactivity for FAM83B was detected in the cytoplasm and near plasma membranes (arrowheads) in SCC, but were hardly detected in Ad and NC. Scale bars, 100 μm.

Figure 2

Immunohistochemical quantification of the family with sequence similarity 83 member B (FAM83B) expression and association with clinical outcomes among squamous cell carcinoma (SCC) patients. (A–D) Immunohistochemical images for FAM83B with (A) high, (B) medium, and (C) low intensities. During the imaging process, cancer regions (dotted line) were extracted and their average intensities were measured. (D) Values for 107 SCC clinical samples are shown as a histogram. Patients were divided in FAM83B-high and -low expression groups. Kaplan-Meier curves for (E) disease-free survival (DFS) and (F) overall survival (OS) in the high (blue line) and low (red line) expression groups. Statistical analysis was performed using the log-rank test.

Figure 2

Immunohistochemical quantification of the family with sequence similarity 83 member B (FAM83B) expression and association with clinical outcomes among squamous cell carcinoma (SCC) patients. (A–D) Immunohistochemical images for FAM83B with (A) high, (B) medium, and (C) low intensities. During the imaging process, cancer regions (dotted line) were extracted and their average intensities were measured. (D) Values for 107 SCC clinical samples are shown as a histogram. Patients were divided in FAM83B-high and -low expression groups. Kaplan-Meier curves for (E) disease-free survival (DFS) and (F) overall survival (OS) in the high (blue line) and low (red line) expression groups. Statistical analysis was performed using the log-rank test.

Figure 2

Immunohistochemical quantification of the family with sequence similarity 83 member B (FAM83B) expression and association with clinical outcomes among squamous cell carcinoma (SCC) patients. (A–D) Immunohistochemical images for FAM83B with (A) high, (B) medium, and (C) low intensities. During the imaging process, cancer regions (dotted line) were extracted and their average intensities were measured. (D) Values for 107 SCC clinical samples are shown as a histogram. Patients were divided in FAM83B-high and -low expression groups. Kaplan-Meier curves for (E) disease-free survival (DFS) and (F) overall survival (OS) in the high (blue line) and low (red line) expression groups. Statistical analysis was performed using the log-rank test.