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. 2023 Mar 31:14:1093042.
doi: 10.3389/fendo.2023.1093042. eCollection 2023.

ncRNA-mediated upregulation of FAM83A is associated with poor prognosis and immune infiltration in pancreatic cancer

Wenbo Zou  1 , Hao Wang  2 , Dingguo Wu  1 , Yunyang Wu  1 , Kuiping Zhou  1 , Yuanshu Lian  1 , Gengyun Chang  1 , Yuze Feng  1 , Jifeng Liang  1 , Gao Huang  1
Affiliations

ncRNA-mediated upregulation of FAM83A is associated with poor prognosis and immune infiltration in pancreatic cancer

Wenbo Zou et al. Front Endocrinol (Lausanne). .

Abstract

Introduction: Malignant pancreatic cancer has poor long-term survival. Increasing evidence shows that FAM83A (family with sequence similarity 83 member A) plays a vital role in tumorigenesis and malignant progression in some human cancer types. The present study explored the potential mechanism of FAM83A in improving the prognosis of pancreatic cancer patients.

Methods: Transcriptomic and clinical data from patients were obtained from The Cancer Genome Atlas while FAM83A expression was measured in tumorous pancreatic tissue compared with normal controls by quantitative real-time PCR and immunohistochemistry.

Results: FAM83A is a vital prognostic indicator and potential oncogene in pancreatic cancer via pan-cancer analysis. In silico analysis revealed that AL049555.1/hsa-miR-129-5p axis was the pivotal upstream ncRNA- mediated pathway of FAM83A in pancreatic cancer. Furthermore, FAM83A expression was related to immune cell infiltration through vital immune-related genes including programmed cell death 1 (PDCD1), and tumorigenesis through common mutation genes including KRAS protooncogene GTPase (KRAS), and SMAD family member 4 (SMAD4). In summary, ncRNA-mediated upregulation of FAM83A is associated with poor long-term survival and immune cell infiltration in pancreatic cancer.

Discussion: FAM83A may be used as a novel survival-related and immune-related biomarker. This information suggests that FAM83A may be a novel therapeutic target for combined or individual treatment for patients with pancreatic cancer.

Keywords: FAM83A; immune cell infiltration; immunotherapy; pancreatic cancer; prognosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Expression analysis for FAM83A in multiple cancers: (A) The expression of FAM83A in human cancers based on TCGA database. (B–H) The differential expression of FAM83A between tumor and normal tissues in TCGA and GTEx: (B) BLCA (C), CESC (D), HNSC (E), LUAD (F), LUSC (G), PAAD (H), ESCA. *p value < 0.05; **p value < 0.01; ***p value < 0.001.
Figure 2
Figure 2
The overall survival (OS) and univariate Cox regression analysis for FAM83A in 6 human cancers based on TCGA: (A–C) The OS plot of FAM83A in LUAD (A), PAAD (B), LUSC (C). (D) the OS forest plot. (E) the DSS forest plot. (F) the DFI forest plot. (G) the PFI forest plot.
Figure 3
Figure 3
The laboratory experiment and clinical significance of FAM83A in PAAD: (A–D) The laboratory experiment. (A) The qRT-PCR result of FAM83A between the tumor and normal tissues. (B) The Immunohistochemistry (IHC) staining plot in PC. (C) The IHC staining plot in para-cancerous tissue. (D) The IHC staining plot in normal tissue. (E-J) clinical significance of FAM83A. (E) The correlation analysis of FAM83A with AJCC stage. (F) Univariate Cox regression analysis. (G) Multivariate Cox regression analysis. (H) The nomogram based on FAM83A expression and N stage. (I) The multivariate ROC curves. (J) The calibration curves at 1-, 2-, 3- years. **p value < 0.01; ***p value < 0.001.
Figure 4
Figure 4
Identification of hsa−miR−129−5p as a potential upstream miRNA of FAM83A in PC.
Figure 5
Figure 5
Expression analysis and survival analysis for AL049555.1, and relationship among AL049555.1/hsa−miR−129−5p/FAM83A axis: (A) The expression of AL049555.1 based on TCGA and GTEx. (B-C) survival analysis of OS and RFS for AL049555.1. (D) The AL049555.1 was strong negatively corelated with hsa-miR-129-5p. (E) The AL049555.1 was strong positively corelated with FAM83A. (F) hsa-miR-129-5p was strong negatively corelated with FAM83A. *p value < 0.05.
Figure 6
Figure 6
Immune cell infiltration (ICI) analysis: (A-B) The relationship of FAM83A expression with ICI in PC. (A) Memory B cells. (B) Macrophages M0. (C) ICI level under copy numbers variation of FAM83A in PC. *p value < 0.05; **p value < 0.01.
Figure 7
Figure 7
Correlation of FAM83A expression with immune-related biomarkers and common mutation genes: (A) Immunostimulatory factors. (B) Immunoinhibitory factors. (C) Chemokines. (D) Chemokine receptors. (E) Mutation genes. Red numbers are considered correlation coefficients.
Figure 8
Figure 8
The model of AL049555.1/hsa−miR−129−5p/FAM83A axis in tumorigenesis of PC.
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