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Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (4): 628-635. doi: 10.19723/j.issn.1671-167X.2022.04.008

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Expression and significance of fibroblast growth factor receptor 2 in clear cell renal cell carcinoma

Tian-yu CAI,Zhen-peng ZHU,Chun-ru XU,Xing JI,Tong-de LV,Zhen-ke GUO,Jian LIN*()   

  1. Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Can-cer Center, Beijing 100034, China
  • Received:2022-04-05 Online:2022-08-18 Published:2022-08-11
  • Contact: Jian LIN E-mail:linjianbj@163.com
  • Supported by:
    the National Natural Science Foundation of China(82070704)

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Abstract:

Objective: To investigate the expression of fibroblast growth factor receptor 2 (FGFR2) in clear cell renal cell carcinoma (ccRCC; or kidney renal clear cell carcinoma, KIRC), to analyze the relationship between the expression of FGFR2 and the clinical pathological features and prognosis of ccRCC, to study the relationship between the expression of FGFR2 and other molecules, and to explore its role in the development of ccRCC. Methods: Gene expressional and clinical information of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus(GEO) database. Next, the data were transformed and collated. In the study, 104 clinical ccRCC samples and corresponding paracancerous normal tissue samples were collected from Department of Urology, Peking University First Hospital. Immunohistochemistry (IHC) was performed and the staining results were scored, so as to compare the expression of FGFR2 in ccRCC and paracancerous normal tissues. Besides, quantify real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of FGFR2 in normal renal epithelial cell lines (293) and ccRCC cell lines (786-O, 769-P, OSRC-2, Caki-1, ACHN, and A498). In addition, the relationship between FGFR2 expression and clinical pathological characteristics (including TNM staging and pathological grading) and survival prognosis in ccRCC patients was further analyzed. Furthermore, the relationship between FGFR2 expression and B cells, T cells, natural killer (NK) cells and neutrophil infiltration in the ccRCC patients was analyzed, and the Biological General Repository for Interactionh Datasets (BioGRID) was used to builds protein-protein interaction (PPI) networks to study molecules that interacted with the FGFR2 protein. Results: In the TCGA database, the expression of FGFR2 was down-regulated in ccRCC tissue samples compared with normal tissue samples, and the expression in the GEO database also showed this differences. Furthermore, FGFR2 expression was downregulated in ccRCC clinical samples and ccRCC cell lines, compared with corresponding paracancerous normal tissue or normal renal epithelial cell lines. In addition, FGFR2 high expression was associated with earlier, lower-level ccRCC and was associated with a better prognosis in the patients with ccRCC. Moreover, FGFR2 expression was not significantly related to B cells, T cells, NK cells and neutrophil infiltration, and the PPI network showed that FGFR2 protein interacted with certain molecules. Conclusion: Our work sheds light on the potential role of FGFR2 in the development of ccRCC, suggesting that FGFR2 may serve as a prognostic marker and potential therapeutic target for patients with ccRCC.

Key words: Fibroblast growth factor receptor 2, Clear cell renal cell carcinoma, Biomarker

CLC Number: 

  • R34

Figure 1

FGFR2 mRNA expression levels in ccRCC tumor samples and normal tissues in the TCGA database △P < 0.001;TCGA, The Cancer Genome Atlas; ccRCC, clear cell renal cell carcinoma; FGFR2, fibroblast growth factor receptor 2; TPM, transcripts per kilobase of exonmodel per million mapped reads."

Figure 2

FGFR2 mRNA expression levels in ccRCC tumor samples and normal tissues in the GEO database # P < 0.01; △ P < 0.001; ccRCC, clear cell renal cell carcinoma; FGFR2, fibroblast growth factor receptor 2; GEO, Gene Expression Omnibus database."

Figure 3

Immunohistochemical staining of FGFR2 in normal tissues and ccRCC tissues (IHC ×40) A, normal tissues; B, ccRCC tissues. ccRCC, clear cell renal cell carcinoma; FGFR2, fibroblast growth factor receptor 2; IHC, immunohistochemistry."

Figure 4

Relative mRNA expression of FGFR2 in ormal cell lines (293)and RCC cell line *P < 0.05;# P < 0.01; △ P < 0.001; RCC, renal cell carcinoma; FGFR2, fibroblast growth factor receptor 2."

Table 1

Baseline data of patients with ccRCC in the TCGA database"

Items Low expression of FGFR2(n=269) High expression of FGFR2(n =270) P
T stage, n (%) 0.001
    T1 117 (21.7) 161 (29.9)
    T2 46 (8.5) 25 (4.6)
    T3 100 (18.6) 79 (14.7)
    T4 6 (1.1) 5 (0.9)
N stage, n (%) 1.000
    N0 128 (49.8) 113 (44.0)
    N1 9 (3.5) 7 (2.7)
M stage, n (%) 1.000
    M0 216 (42.7) 212 (41.9)
    M1 39 (7.7) 39 (7.7)
Pathologic stage, n (%) 0.002
    Stage Ⅰ 115 (21.5) 157 (29.3)
    Stage Ⅱ 36 (6.7) 23 (4.3)
    Stage Ⅲ 74 (13.8) 49 (9.1)
    Stage Ⅳ 42 (7.8) 40 (7.5)
OS event, n (%) 0.009
    Alive 168 (31.2) 198 (36.7)
    Dead 101 (18.7) 72 (13.4)
Age, M (IQR) 61 (52, 70) 60 (51, 69) 0.241

Figure 5

Relationship of FGFR2 expression in patients with ccRCC in the TCGA database with tumor TNM staging, pathological grading, and OS *P < 0.05;# P < 0.01; △ P < 0.001; ccRCC, clear cell renal cell carcinoma; FGFR2, fibroblast growth factor receptor 2; OS, overall survival; TPM, transcripts per kilobase of exonmodel per million mapped reads."

Figure 6

FGFR2 expression and B cells, T cells, NK cells and neutrophils infiltration in patients with ccRCC A, T cells; B, neutrophils; C, B cells; D, NK cells. FGFR2, fibroblast growth factor receptor 2;TPM, transcripts per kilobase of exonmodel per million mapped reads; NK, natural killer; ccRCC, clear cell renal cell carcinoma."

Figure 7

Protein interaction network of FGFR2 FGFR1, fibroblast growth factor receptor 1; FGFR2, fibroblast growth factor receptor 2."

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