Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jun 18:10:1585-1596.
doi: 10.2147/CMAR.S160186. eCollection 2018.

INHBA upregulation correlates with poorer prognosis in patients with esophageal squamous cell carcinoma

Shanshan Lyu  1   2 , Chao Jiang  3 , Rui Xu  4 , Yuhua Huang  1 , Shumei Yan  1
Affiliations

INHBA upregulation correlates with poorer prognosis in patients with esophageal squamous cell carcinoma

Shanshan Lyu et al. Cancer Manag Res. .

Abstract

Purpose: INHBA, which encodes a member of the TGF-beta superfamily of proteins, has been identified to play a critical role in different types of cancer. However, its clinical significance in esophageal squamous cell carcinoma (ESCC) has never been reported.

Patients and methods: In this study, we collected 239 ESCC paraffin-embedded specimens and measured the expression of INHBA with immunohistochemistry (IHC). The clinical and prognostic significance of INHBA expression was statistically analyzed. What is more, we conducted a meta-analysis to study the prognostic value of INHBA expression in multiple types of solid tumors.

Results: The results showed that INHBA expression was observed predominantly in the cytoplasm of cells in the ESCC specimens. INHBA expression was closely correlated with N categories (P=0.026). Kaplan-Meier analysis showed that ESCC patients in the low INHBA expression subgroup had significantly better prognosis than those with high INHBA level. Subgroup analysis revealed that INHBA distinguished the disease-free survival (DFS) and overall survival (OS) when patients were stratified by TNM stage status and N status. Multivariate analysis results suggested that INHBA expression was an independent factor that affected OS (HR =1.679, P=0.022) and DFS (HR =1.715, P=0.017). In the meta-analysis, six papers with 1321 patients were included and patients with high INHBA level had worse prognosis than patients with low INHBA level (HR 2.50, 95% CI 1.75-3.57, P<0.0001).

Conclusion: High INHBA level predicts poor prognosis in ESCC and other solid tumors. More studies are required to elucidate the role of INHBA and its clinical application in cancer settings.

Keywords: ESCC; INHBA; meta-analysis; prognosis.

PubMed Disclaimer

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flow chart of meta-analysis literature search.
Figure 2
Figure 2
Meta-analysis plots. Notes: Forest plot of HR for the association of high plasma INHBA level and survival (A). Begg’s funnel plots of publication bias (B). Abbreviation: UTC, upper tract urothelial carcinoma.
Figure 3
Figure 3
INHBA expression determined by IHC. Notes: Normal esophageal tissue demonstrated no expression of INHBA protein in the cytoplasm of esophageal squamous cells (magnification: A, ×40; B, ×200). Low expression level of INHBA in ESCC tissues (magnification: C, ×40; D, ×200). Median expression of INHBA in ESCC tissues (magnification: E, ×40; F, ×200). High expression levels of INHBA were detected in ESCC tissues (magnification: G, ×40; H, ×200). Abbreviations: ESCC, esophageal squamous cell carcinoma; IHC, immunohistochemistry.
Figure 4
Figure 4
Disease-free survival (DFS) and overall survival (OS) curves according to patients’ INHBA expression. Notes: DFS curve in all patients with different levels of INHBA expression (A, P=0.001). OS curve in all patients with different levels of INHBA expression (B, P=0.001). DFS and OS curves in patients in TNM stage 1 and 2 with low and high INHBA expression (C, D, P=0.009 and P=0.008, respectively). DFS and OS curves in patients in N0 stage with low and high INHBA expression (E, F, P=0.022 and P=0.023, respectively).
See this image and copyright information in PMC

References

    1. Okano M, Yamamoto H, Ohkuma H, et al. Significance of INHBA expression in human colorectal cancer. Oncol Rep. 2013;30(6):2903–2908. - PubMed
    1. Wang Q, Wen YG, Li DP, et al. Upregulated INHBA expression is associated with poor survival in gastric cancer. Med Oncol. 2012;29(1):77–83. - PubMed
    1. Lee HY, Li CC, Huang CN, et al. INHBA overexpression indicates poor prognosis in urothelial carcinoma of urinary bladder and upper tract. J Surg Oncol. 2015;111(4):414–422. - PubMed
    1. Oshima T, Yoshihara K, Aoyama T, et al. Relation of INHBA gene expression to outcomes in gastric cancer after curative surgery. Anticancer Res. 2014;34(5):2303–2309. - PubMed
    1. Katayama Y, Oshima T, Sakamaki K, et al. Clinical significance of INHBA gene expression in patients with gastric cancer who receive curative resection followed by adjuvant S-1 chemotherapy. In Vivo. 2017;31(4):565–571. - PMC - PubMed

LinkOut - more resources