Overexpression of P4HB is correlated with poor prognosis in human clear cell renal cell carcinoma

Zhu, Zhenpeng; He, Anbang; Lv, Tianjing; Xu, Chunru; Lin, Lanruo; Jian, Lin

doi:10.3233/cbm-190450

Cited by 27 publications

(27 citation statements)

References 20 publications

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“…20 P4HB is highly expressed in renal clear cell carcinoma (ccRCC) and positively correlated with pathological grade, stage and poor prognosis; it has been verified as an independent risk factor by multifactor Cox regression in ccRCC. 14 In addition, logistic regression and chi-square tests were conducted in 80 BC patients and TCGA database patients and indicated that P4HB overexpression in tissues is strongly associated with the clinicopathological characteristics of BC. Most importantly, BC patients with higher P4HB expression had a worse prognosis than those with lower expression.…”

Section: Discussionmentioning

confidence: 99%

“…The final score was obtained by multiplying the staining intensity score and the staining proportion score. BC patients were categorized as either the low P4HB expression group (1)(2)(3)(4)(5)(6)(7)(8) or the high P4HB expression group (9)(10)(11)(12)(13)(14)(15)(16).…”

Section: Tcga Database Analysismentioning

confidence: 99%

“…13 High P4HB expression is associated with poor clinical prognosis of renal clear cell carcinoma and hepatocellular carcinoma. 14,15 Inhibition of P4HB increases the chemosensitivity of temozolomide-resistant glioma cells and sensitizes glioma cells to radiotherapy. 9,16 In our study, we determined that P4HB was significantly overexpressed in BC tissues compared with adjacent normal tissues.…”

Section: Introductionmentioning

confidence: 99%

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Targeted Inhibition of P4HB Promotes Cell Sensitivity to Gemcitabine in Urothelial Carcinoma of the Bladder

Wang¹,

Bai²,

Yang³

et al. 2020

OTT

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Background: Bladder cancer (BC) is a common malignancy worldwide that accounts for 3% of global cancer diagnoses. Chemotherapy resistance limits the therapeutic effect of chemotherapeutic agents in patients with BC. Prolyl 4-hydroxylase, beta polypeptide (P4HB) is an endoplasmic reticulum (ER) chaperone that is upregulated in bladder cancer tissues (The Cancer Genome Atlas, TCGA datasets). Knockdown or suppression of P4HB exerts anticancer activity and sensitizes cells to chemotherapy in various types of cancer. Purpose: We aimed to investigate whether the inhibition of P4HB enhances the anticancer efficacy of gemcitabine (GEM) in BC cells and to study the underlying molecular mechanisms. Patients and Methods: The P4HB mRNA expression levels of 411 BC patients from the TCGA database and P4HB expression level of eighty BC paraffin-embedded samples detected by immunohistochemistry (IHC) staining were used for clinical feature and prognostic analyses. Bioinformatics analysis was utilized for the mechanistic investigation. Highly P4HB-expressed BC cell lines (T24 and 5637) treated with P4HB inhibitor (Bacitracin, BAC) were used to study the effects of BAC on the sensitivity of BC cells to GEM and the potential mechanism. P4HB inhibition experiments were performed in highly P4HB-expressed BC cells, and cell viability, colony formation, cell cycle, reactive oxygen species (ROS), apoptosis and pathway proteins were assessed in T24 and 5637 cells. Results: Western blot analysis showed that P4HB expression was significantly higher in BC tissues than in paired normal tissues. IHC showed that patients with high P4HB expression had a poorer overall survival (OS) rate than those with low P4HB expression. Furthermore, increased P4HB expression was demonstrated to be an independent prognostic marker for BC. Functionally, P4HB inhibition by BAC decreased the cell proliferation ability in vitro. Moreover, BAC treatment sensitized BC cells to GEM. Molecular mechanism analysis indicated that inhibition of P4HB by BAC treatment enhanced the anticancer effects of GEM through increasing cellular ROS content and promoting cell apoptosis and PERK/eIF2α/ATF4/CHOP signaling. Conclusion: High P4HB expression was significantly correlated with poor prognosis in BC patients. Inhibition of P4HB by BAC decreased the cell proliferation ability and sensitized BC cells to GEM by activating apoptosis and the PERK/eIF2α/ATF4/CHOP pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Tcga Database Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Targeted Inhibition of P4HB Promotes Cell Sensitivity to Gemcitabine in Urothelial Carcinoma of the Bladder

Wang¹,

Bai²,

Yang³

et al. 2020

OTT

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“…The multiplication of these two variables was calculated as a final score: 0 (score 0-3); 1 (score 4-6); 2 (score 7-9); or 3 (score 10-12). 14…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Prognostic Value and Potential Biological Functions of CLDN8 in Patients with Clear Cell Renal Cell Carcinoma

Zhu¹,

Lin³

et al. 2020

OTT

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Purpose: Clear cell renal cell carcinoma (ccRCC) is among the most common malignant tumors worldwide, with a high incidence rate and poor prognosis. Currently, there are no biomarkers that can accurately guide prognostic evaluation and therapeutic strategy for ccRCC. The prognostic value and potential biological function of claudin-8 (CLDN8), a critical component of tight junctions in ccRCC, remain unclear. Methods: Sequencing data were obtained from The Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. R packages were used to explore CLDN8 mRNA expression levels and analyze differentially expressed genes. Results were validated in clinical specimens and cell lines, and bioinformatics analyses were conducted to explore the potential biological functions of CLDN8. Finally, functional analyses were carried out using 786-O ccRCC cell line. Results: Both CLDN8 mRNA and protein expression levels were significantly lower in ccRCC compared with the normal control tissues. Kaplan-Meier analyses showed that low CLDN8 expression levels were associated with the poor overall survival, while univariate and multivariate Cox regression indicated that CLDN8 could serve as an independent prognostic factor in patient with ccRCC. Bioinformatic and Western blot analyses showed that CLDN8 suppressed proliferation, migration, and invasion of 786-O ccRCC cells through the epithelial-mesenchymal transition and AKT pathways. Conclusion: CLDN8 could serve as an independent prognostic factor in ccRCC, in which it suppresses 786-O proliferation, migration, and invasion through EMT and AKT pathways.

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“…The staining intensity was classified as 0 (no staining), 1 (weak), 2 (moderate) or 3 (strong); The proportion of stained tumor cells was scored as 0 (0-5%), 1 (6-25%), 2 (26-50%), 3 (51-75%), 4 (>75%). The product of these two variables was used to calculate a final score based on a previous study (26), as follows: 0 (product of 0-3); 1 (product of 4-6); 2 (product of 7-9); 3 (product of 10-12).…”

Section: Extraction Of Clinical and Gene Expression Data From The Ccrmentioning

confidence: 99%

High expression levels of DEF6 predicts a poor prognosis for patients with clear cell renal cell carcinoma

Zhu

Lin

et al. 2020

Oncol Rep

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Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignant tumors and early detection contributes to a better prognosis. Finding new biomarkers for the diagnosis or treatment remains meaningful. DEF6 guanine nucleotide exchange factor (DEF6) is upregulated in ccRCC compared to normal controls, but the relationship between DEF6 expression and prognosis in ccRCC is unclear. Moreover, the potential biological functions of DEF6 in ccRCC remains unclear. In the present study, the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), TISIDB and the clinical database of the Peking University First Hospital were used to analyze DEF6 expression in ccRCC. Immunohistochemistry (IHC), western blotting and reverse transcription-quantitative PCR were used to examine the DEF6 protein and mRNA expression levels in cell lines and clinical samples. Subsequently, the Kaplan-Meier method and Cox regression analyses were used to determine the impact of DEF6 expression on the overall survival of patients alongside other clinical variables in both the TCGA database and the present clinical database. The results showed that both DEF6 mRNA and protein expression levels were upregulated in ccRCC compared to normal controls. The Kaplan-Meier survival analysis showed that patients with high DEF6 expression had poor prognoses from both the TCGA database and the present clinical database. Univariate survival analysis and multivariate survival analysis revealed that DEF6 could be an independent prognostic factor for ccRCC. Additionally, bioinformatics analysis indicated that differentially expressed genes related to DEF6 expression influenced ccRCC by regulating the tumor immune microenvironment. In conclusion, overexpression of DEF6 is significantly correlated with a poor prognosis for patients with ccRCC and DEF6 may influence the biological processes involved with ccRCC by regulating the immune microenvironment.

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Overexpression of P4HB is correlated with poor prognosis in human clear cell renal cell carcinoma

Cited by 27 publications

References 20 publications

<p>Targeted Inhibition of P4HB Promotes Cell Sensitivity to Gemcitabine in Urothelial Carcinoma of the Bladder</p>

<p>Targeted Inhibition of P4HB Promotes Cell Sensitivity to Gemcitabine in Urothelial Carcinoma of the Bladder</p>

<p>Prognostic Value and Potential Biological Functions of CLDN8 in Patients with Clear Cell Renal Cell Carcinoma</p>

High expression levels of DEF6 predicts a poor prognosis for patients with clear cell renal cell carcinoma

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