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Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastric Cancer
Lei Yang
Nantong Tumor Hospital
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) are represent for poor prognosis of various cancers. However, rare research investigate the correlation of them in cancer. This study aimed to investigate the correlation and prognostic value of P4HB and GRP78 expression along with clinical features in gastric cancer (GC).
Methods: A total of 150 GC tissue samples separately evaluated P4HB and GRP78 protein expression by immunohistochemistry. Association of P4HB and GRP78 expression with clinicopathological features was analyzed. Bioinformatics analyses were performed to find correlation between mRNAs and pathways. Kaplan-Meier analyses were taken to compare survival curves. Univariate and multivariate Cox regression models used to analyze the impact of prognostic factors on overall survival (OS). A prognostic nomogram was constructed based on the multivariate Cox regression model, and compared to TNM stage in discrimination ability and clinical usefulness.
Results: P4HB and GRP78 expression were both associated with tumor invasion and lymph node metastasis. P4HB protein positively correlated with GRP78, as well as the same tendency of mRNAs in both GC tissue and cell databases. Bioinformatics analyses indicated that P4HB and GRP78 may be associated with protein folding and response to ER stress, and the protein processing in ER pathway. High single or co-expression of P4HB and GRP78 represented for a shorter OS. When stratified by postoperative adjuvant chemotherapy, the high co-expression was only related to unfavorable prognosis of with chemotherapy group, especially in advanced stage. Multivariate Cox regression analysis identified co-expression of P4HB and GRP78 as an independent prognostic factor for OS. The nomogram including the co-expression was better than TNM stage in discrimination ability and clinical usefulness through the receiver operating characteristic (ROC) and decision curve analysis (DCA) curves.
Conclusion: P4HB was positively correlated with GRP78 expression, co-expression of them was an independent prognostic factor, could serve as a predictive marker for GC patients with postoperative adjuvant chemotherapy in advanced stage.
Keywords
P4HB, GRP78, gastric cancer, postoperative adjuvant chemotherapy, nomogram
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This preprint is under consideration at Cancer Cell International. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Primary research
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastric Cancer
Lei Yang
Nantong Tumor Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 22 Jun, 2020
No community comments so far
Submission checks complete
On 19 Jun, 2020
First submitted
On 18 Jun, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) are represent for poor prognosis of various cancers. However, rare research investigate the correlation of them in cancer. This study aimed to investigate the correlation and prognostic value of P4HB and GRP78 expression along with clinical features in gastric cancer (GC).
Methods: A total of 150 GC tissue samples separately evaluated P4HB and GRP78 protein expression by immunohistochemistry. Association of P4HB and GRP78 expression with clinicopathological features was analyzed. Bioinformatics analyses were performed to find correlation between mRNAs and pathways. Kaplan-Meier analyses were taken to compare survival curves. Univariate and multivariate Cox regression models used to analyze the impact of prognostic factors on overall survival (OS). A prognostic nomogram was constructed based on the multivariate Cox regression model, and compared to TNM stage in discrimination ability and clinical usefulness.
Results: P4HB and GRP78 expression were both associated with tumor invasion and lymph node metastasis. P4HB protein positively correlated with GRP78, as well as the same tendency of mRNAs in both GC tissue and cell databases. Bioinformatics analyses indicated that P4HB and GRP78 may be associated with protein folding and response to ER stress, and the protein processing in ER pathway. High single or co-expression of P4HB and GRP78 represented for a shorter OS. When stratified by postoperative adjuvant chemotherapy, the high co-expression was only related to unfavorable prognosis of with chemotherapy group, especially in advanced stage. Multivariate Cox regression analysis identified co-expression of P4HB and GRP78 as an independent prognostic factor for OS. The nomogram including the co-expression was better than TNM stage in discrimination ability and clinical usefulness through the receiver operating characteristic (ROC) and decision curve analysis (DCA) curves.
Conclusion: P4HB was positively correlated with GRP78 expression, co-expression of them was an independent prognostic factor, could serve as a predictive marker for GC patients with postoperative adjuvant chemotherapy in advanced stage.
Figure 1
Figure 2
Figure 3
Figure 4