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Identification of LIPH as an unfavorable biomarkers correlated with immune suppression or evasion in pancreatic cancer based on RNA-seq

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Abstract

Background

It is widely considered that pancreatic cancer (PC) is an immunosuppressive cancer. Immune-based therapies remain promising therapeutic strategies for PC. Overexpression of lipase H (LIPH) was reported to be related to immunity in cattle and has also been demonstrated to promote tumor progression in several tumors, but its role in pancreatic carcinogenesis remains unclear. Study on LIPH in PC might provide a new insight into the immunosuppression in PC.

Methods

The potential biological and clinical significance of LIPH was evaluated by bioinformatics analysis. We further investigated potential associations between the expression of LIPH and tumor immune infiltration using the CIBERSORT algorithm, the ESTIMAT algorithm, and single sample gene set enrichment analysis (ssGSEA).

Results

LIPH was significantly overexpressed in tumor tissues compared with normal tissues. LIPH overexpression correlated with tumor recurrence, advanced histologic grade, and poorer overall survival (OS). Four of the most common somatic mutation, including KRAS, TP53, CDKN2A, and SMAD4, in PC were all correlated with high LIPH expression. And high LIPH expression was significantly correlated with KRAS activation and SMAD4 inactivation. Besides, LIPH expression was involved in various biological pathways such as negative regulation of cell–cell adhesion, actin cytoskeleton, EMT, angiogenesis, and signaling by MST1. And LIPH overexpression caused high infiltration of TAMs, Treg cells, and Th2/Th1, but reduced the infiltration of CD8+ T cells and Th1 cells.

Conclusions

Our findings demonstrated that LIPH correlated with immune suppression or evasion and may function as a novel unfavorable prognostic biomarker in PC.

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Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary.

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Acknowledgements

This study was supported by High-level Hospital Construction Project (DFJH201921), Fundamental Research Funds for the Central Universities (y2syD2192230), and National Natural Science Foundation of China (Nos. 81672475, 81702783, 82072635 and 82072637).

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510080, China

    Hongkai Zhuang

  2. Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Guangzhou, 510080, China

    Hongkai Zhuang, Shanzhou Huang, Chuanzhao Zhang & Baohua Hou

  3. Department of Hepatobiliary Surgery, Shenshan Central Hospital, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Shanwei, 516600, China

    Xinming Chen

  4. The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, 310006, China

    Ying Wang

  5. Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Guangzhou, 510080, China

    Bo Chen

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  1. Hongkai Zhuang
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  5. Bo Chen
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Contributions

HZ, BC, CZ, and BH conceived and designed the study. HZ, XC, and YW performed the data analysis. HZ, XC, BC, and SH wrote the paper. All authors read and approved the manuscript.

Corresponding authors

Correspondence to Bo Chen, Chuanzhao Zhang or Baohua Hou.

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Conflict of interest

All authors declare that they have no conflicts of interest.

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All datasets are freely available as public resources. Therefore, local ethics approval was not needed.

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Hongkai Zhuang, Xinming Chen and Ying Wang co-first authors.

Supplementary Information

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Figure S1

KM survival analysis for OS of PC patients in TCGA dataset according to the median of LIPH expression. KM, Kaplan-Meier; PC, pancreatic cancer; OS, overall survival; HR, hazard ratio (TIF 3189 kb)

Figure S2

The mutation landscape of PC in TCGA dataset. PC, pancreatic cancer (TIF 6564 kb)

Figure S3

Validation of the association among LIPH, KRAS, and SMAD4 using cBioportal database. (A) LIPH expression was positively correlated to KRAS expression (Cor=0.51, P<0.05). (B) LIPH expression was negatively correlated to SMAD4 expression (Cor=-0.43, P<0.05) (TIF 1823 kb)

Figure S4

Association between LIPH expression and TMB. TMB, the total mutational burden (TIF 299 kb)

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Zhuang, H., Chen, X., Wang, Y. et al. Identification of LIPH as an unfavorable biomarkers correlated with immune suppression or evasion in pancreatic cancer based on RNA-seq. Cancer Immunol Immunother 71, 601–612 (2022). https://doi.org/10.1007/s00262-021-03019-x

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