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Protein interacting with C-kinase 1 is involved in epithelial-mesenchymal transformation and suppresses progress of gastric cancer

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Abstract

Protein interacting with C-kinase 1 (PICK1) is a 415-aa multidomain scaffold protein encoded by the PICK1 gene. Accumulating evidence suggests that PICK1 is involved in the progression of cancer. However, the role of PICK1 in gastric cancer (GC) remains largely unknown. Using integrated analysis of publicly available GC transcriptome data from the Gene Expression Omnibus (GEO) database and immunohistochemistry analysis of samples obtained from clinical GC patients, we found that PICK1 expression was significantly down-regulated in gastric tumor tissues in comparison with adjacent normal tissues. Our analyses also revealed that decreased expression of PICK1 conferred a disadvantage on overall survival time in GC patients. Additionally, PICK1 expression showed a strong association with the epithelial-mesenchymal transition (EMT) pathway, and PICK1 might represent a functional bridge for EMT. Moreover, PICK1 expression was significantly decreased in the EMT subtype of GC and was negatively correlated with the expression of fibronectin 1 (FN1) and myosin light chain 9 (MYL9) mRNAs. Thus, our study provides evidence that PICK1 is a promising biomarker for the molecular etiology of GC.

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Acknowledgements

This work was supported by the Traditional Chinese Medicine Scientific Research Foundation of Zhejiang Province (2018ZY001), the National Natural Science Foundation of China (81772664, 81830071), the Natural Science Foundation of Zhejiang Province (LQ21H200007), and the Medicine and Health Research Foundation of Zhejiang Province (2019KY017, WKJ-ZJ-2019, 2019RC012).

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Author notes

  1. Ying Zhou, Kaiqiang Li, and Yaoqiang Du have contributed equally to this work.

Authors and Affiliations

  1. Research Center of Blood Transfusion Medicine, Ministry of Education Key Laboratory of Laboratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, China

    Ying Zhou, Kaiqiang Li, Yaoqiang Du, Ke Hao & Zhen Wang

  2. School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, China

    Ying Zhou, Zhaoyu Wu, Hao Wang, Yexiaoqing Yang & Jianxin Lyu

  3. Rehabilitation and Sports Medicine Research Institute of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, China

    Kaiqiang Li, Yaoqiang Du, Ke Hao, Zhen Wang & Jianxin Lyu

  4. Department of Pathology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, China

    Xin Zhang

  5. School of Laboratory Medicine, Hangzhou Medical College, Hangzhou, 310053, China

    Linjie Chen & Jianxin Lyu

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  1. Ying Zhou
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Correspondence to Zhen Wang or Jianxin Lyu.

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The study was performed in obedience to the ethical guidelines of the Declaration of Helsinki and obtained the approval from the Ethics Committee of Zhejiang Provincial People’s Hospital (2020QT312).

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Supplementary Information

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12032_2021_1483_MOESM1_ESM.pdf

Supplementary file 1 (PDF 761 KB) Supplementary Fig. 1 PICK1 mRNA is correlated with EMT in GC. a–f. Gene sets positively related to EMT were enriched in the low-PICK1 mRNA group. g. Gene set negatively related to EMT was enriched in the high-PICK1 mRNA group

12032_2021_1483_MOESM2_ESM.pdf

Supplementary file 2 (PDF 1976 KB) Supplementary Fig. 2 Validation on TCGA and GTEx. a. PICK1 mRNA level was down-regulated in GC as revealed by TCGA and GTEx. b–f. PICK1 mRNA level was negatively correlated with FN1 (b), MYL9 (c), N-cadherin (d), Vimentin (e), and positively correlated with E-cadherin (f) in TCGA

12032_2021_1483_MOESM3_ESM.xlsx

Supplementary file 3 (XLSX 80 KB) Supplementary Table 1 Expression of PICK1 mRNA and clinical information of GC in GEO datasets and the gene signature members

12032_2021_1483_MOESM4_ESM.doc

Supplementary file 4 (DOCX 98 KB) Supplementary Table 2 Correlations between PICK1 expression level and clinicopathologic parameters in gastric cancer patients

12032_2021_1483_MOESM5_ESM.xlsx

Supplementary file 5 (XLSX 76 KB) Supplementary Table 3 Differentially expressed genes and functional enrichment results of DEGs

Supplementary file 6 (XLSX 39 KB) Supplementary Table 4 Basic information of 17 EMT-related gene sets and GSEA results

Supplementary file 7 (XLSX 360 KB) Supplementary Table 5 Expression of 64 intersection genes in GSE15459 and GSE62254

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Zhou, Y., Li, K., Du, Y. et al. Protein interacting with C-kinase 1 is involved in epithelial-mesenchymal transformation and suppresses progress of gastric cancer. Med Oncol 38, 34 (2021). https://doi.org/10.1007/s12032-021-01483-0

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