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Role of Up-Regulated Transmembrane Channel-Like Protein 5 in Pancreatic Adenocarcinoma

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Abstract

Background

Pancreatic adenocarcinoma (PAAD) is a malignant tumor responsible for a heavy disease burden. Previously, only one pan-cancer study of Transmembrane channel-like protein 5 (TMC5) showed that TMC5 was highly expressed in PAAD, but the results lacked comprehensive verification, and the mechanism of TMC5 in PAAD was still unclear.

Methods

For exploring the expression and clinical value of TMC5 in PAAD better, we adopted a comprehensive evaluation method, using internal immunohistochemistry (IHC) data combined with microarray and RNA-sequencing data collected from public databases. The single cell RNA-sequencing (scRNA-seq) data were exploited to explore the TMC5 expression in cell populations and intercellular communication. The potential mechanism of TMC5 in PAAD was analyzed from the aspects of immune infiltration, transcriptional regulation, function and pathway enrichment.

Results

Our IHC data includes 148 PAAD samples and 19 non-PAAD samples, along with the available microarray and RNA-sequencing data (1166 PAAD samples, 704 non-PAAD samples). The comprehensive evaluation results showed that TMC5 was evidently up-regulated in PAAD (SMD = 1.17). Further analysis showed that TMC5 was over-expressed in cancerous epithelial cells. Furthermore, TMC5 was up-regulated in more advanced tumor T and N stages. Interestingly, we found that STAT3 as an immune marker of Th17 cells was not only positively correlated with TMC5 and up-regulated in PAAD tissues, but also the major predicted TMC5 transcription regulator. Moreover, STAT3 was involved in cancer pathway of PAAD.

Conclusion

Up-regulated TMC5 indicates advanced tumor stage in PAAD patients, and its role in promoting PAAD development may be regulated by STAT3.

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Data availability

The data supporting the results of this study can be obtained from corresponding author upon reasonable request.

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Acknowledgments

The authors are grateful for the technical support from Guangxi Key Laboratory of Medical Pathology and the data from all the public databases.

Funding

This study was supported by Natural Science Foundation of Guangxi, China (2018GXNSFAA050051), Guangxi Medical High-Level Key Talents Training “139” Program (2020), Guangxi Educational Science Planning Key Project (2021B167), Guangxi Medical University Education and Teaching Reform Project (2021XJGA02), Guangxi Medical University Teacher Teaching Ability Development Project (2202JFA20, 2202JFA02), Guangxi Higher Education Undergraduate Teaching Reform Project (2016JGA167), Guangxi Medical University Student Innovation and Entrepreneurship Training Program (202110598298).

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Authors and Affiliations

  1. Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, No. 6. Shuangyong Rd, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China

    Xiang-Yu Gan, Jian-Di Li, Gang Chen, Jia-Yuan Luo, Jing-Jing Zeng, Zi-Xuan Yang, Yu-Xuan Yao, Jun-Jie Zhu & Dan-Ming Wei

  2. Department of Internal Medicine-Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6. Shuangyong Rd, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China

    Rong-Quan He

  3. Department of Minimally Invasive Surgery, The Second Affiliated Hospital of Guangxi Medical University, No. 166. DaxueDong Rd, Nanning, 530007, Guangxi Zhuang Autonomous Region, People’s Republic of China

    Jian-Jun Li

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All authors have made significant contributions in the process of this study, including research design, experiment development, data collection and analysis, drafting and modification of paper. And all authors have reviewed and approved the submission of the paper.

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Correspondence to Dan-Ming Wei.

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Ethical approval

The study was approved by the Ethics Committees of the First Affiliated Hospital of Guangxi Medical University (2021-KY-GUOJI-115, February 20, 2021) and Guilin Fanpu Biotechand (FANPU[2018]23, October 25, 2018).

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Gan, XY., Li, JD., Chen, G. et al. Role of Up-Regulated Transmembrane Channel-Like Protein 5 in Pancreatic Adenocarcinoma. Dig Dis Sci 68, 1894–1912 (2023). https://doi.org/10.1007/s10620-022-07771-7

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