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. 2022 Aug;11(8):2660-2670.
doi: 10.21037/tcr-22-303.

Clinicopathological significance and prognostic value of polypyrimidine tract binding protein 1 (PTBP1) in gastric cancer

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Clinicopathological significance and prognostic value of polypyrimidine tract binding protein 1 (PTBP1) in gastric cancer

Mengnan Liu et al. Transl Cancer Res. 2022 Aug.

Abstract

Background: Polypyrimidine tract binding protein 1 (PTBP1) is a member of heterogeneous nuclear ribonucleoprotein (hnRNP) family and has recently been reported to contribute to development and progression of various tumors. However, the clinicopathological significance and prognostic value of PTBP1 in gastric cancer have not been sufficiently elucidated.

Methods: Bioinformatic analysis of The Cancer Genome Atlas (TCGA) data were employed to analyze the expression of PTBP1 mRNA and its prognostic value in gastric cancer. The expression type of PTBP1 in gastric cancer cells was further confirmed through reverse transcription polymerase chain reaction (RT-PCR) and western blot assay. Then, the association between PTBP1 protein expression and clinicopathological features was analyzed based on immunohistochemical staining results in gastric cancer tissue microarray including 311 cases. The prognostic value of PTBP1 protein was explored through univariate and multivariate analyses. Additionally, cell count and transwell assay were performed to detect the biological role of PTBP1 in gastric cancer cells in vitro.

Results: PTBP1 was highly expressed in gastric cancer cells and tissues at mRNA and protein level. High expression of PTBP1 was closely related to several clinicopathological features, including gender, age at surgery, histological type, TNM stage and lymph node metastasis. Moreover, high expression PTBP1 predicts poor prognosis, and may be an independent prognostic factor for overall survival in gastric cancer patients. Knockdown of PTBP1 substantially suppressed the proliferation, migration and invasion of gastric cancer cells in vitro.

Conclusions: PTBP1 is up-regulated and predicts poor prognosis in gastric cancer. PTBP1 may serve as a biomarker of poor prognosis and a novel target in treating gastric cancer.

Keywords: Polypyrimidine tract binding protein 1 (PTBP1); gastric cancer (GC); immunohistochemistry; migration; prognosis.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-303/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Bioinformatics analysis of PTBP1 expression and prognostic value in gastric cancer based on TCGA database. (A) PTBP1 mRNA was highly expressed in 375 cases of gastric cancer compared to 32 cases of adjacent non-tumor tissues. (B) PTBP1 mRNA existed at higher level in cancer tissues than adjacent non-tumor tissues in 32 pairs of gastric cancer and corresponding adjacent non-tumor tissues. (C) Survival analyses showed a trend that high level of PTBP1 predicted poor prognosis, but the difference was not statistically significant (P=0.052). ***P<0.001. PTBP1, polypyrimidine tract binding protein 1; TCGA, The Cancer Genome Atlas.
Figure 2
Figure 2
Expression of PTBP1 in gastric cancer cells and tissues. (A) Western blot assay showed that PTBP1 protein and (B) RT-PCR showed that PTBP1 mRNA were elevated in gastric cancer cell lines (AGS, HGC-27, MKN-45 and SGC-7901) compared to gastric mucosal epithelial cell line GES-1. **P<0.01. (C) Immunohistochemical staining on tissue microarray indicated higher PTBP1 protein level in gastric cancer tissues than adjacent non-tumor tissues. Scale bar =10 μm. HE, hematoxylin-eosin; PTBP1, polypyrimidine tract binding protein 1.
Figure 3
Figure 3
The prognostic value and biological role of PTBP1 in gastric cancer. (A) Kaplan-Meier analysis of overall survival for gastric cancer patients showed that gastric cancer patients with high PTBP1 expression had a significantly shorter overall survival (OS) time than those with low expression of PTBP1 (P=0.016). (B) CCK-8 assay showed proliferation ability of gastric cancer cells was significantly abrogated after knocking down PTBP1. **P<0.01. Data are presented as mean ± SD. The experiments were repeated three times. (C) Transwell assays showed the migratory and invasive ability were remarkably reduced in gastric cancer cells after knocking down PTBP1. **P<0.01. Data are presented as mean ± SD. Crystal violet staining. Scale bar =10 μm. The experiments were repeated three times. PTBP1, polypyrimidine tract binding protein 1; CCK-8, cell counting kit-8.

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