GJB4 Gene Expression in Relation to Clinical and Pathological Features of Pancreatic Cancer Patients

Runlin FENG; Zongqi DENG; Mengyao WU; Yunna WANG; Yu WANG; Guilan LIU

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Runlin FENG, Zongqi DENG, Mengyao WU, Yunna WANG, Yu WANG, Guilan LIU. GJB4 Gene Expression in Relation to Clinical and Pathological Features of Pancreatic Cancer Patients[J]. Journal of Kunming Medical University.

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GJB4 Gene Expression in Relation to Clinical and Pathological Features of Pancreatic Cancer Patients

1.
Dept. of Pathology
2.
Dept. of Clinical Laboratory
3.
Dept. of Gastroenterology，The 2nd Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650101，China

Received Date: 2024-04-11
Available Online: 2024-07-04

Abstract

Abstract

Objective To investigate the expression of GJB4 gene in pancreatic cancer tissue and its correlation with clinicopathology. Methods The expression levels of GJB4 mRNA in pancreatic cancer and adjacent cancer tissues were analyzed using bioinformatics to analyze the Cancer Genome Atlas （TCGA） and Genotype-Tissue Expression （GTEx） RNA sequencing datasets. A total of 120 pancreatic cancer samples and 40 adjacent cancer samples from the Pathology Department of The Second Affiliated Hospital of Kunming Medical University from January 2019 to December 2023 were collected and sorted. Immunohistochemistry staining method was used to detect the expression difference of GJB4 protein between the two groups. RT-qPCR method was used to detect the expression levels of GJB4 in four pancreatic cancer cell lines. Univariate and multivariate Cox regression and Kaplan-Meier curves were used to analyze the clinical pathological data of GJB4 and pancreatic cancer patients. DAVID functional annotation bioinformatics and GSEA enrichment analysis were used to explore the relevant pathways of GJB4 in pancreatic cancer. Results The expression level of GJB4 mRNA in pancreatic cancer was higher than that in adjacent tissues, and the high expression of GJB4 was significantly associated with poor prognosis of patients （P < 0.05）. Immunohistochemical analysis showed that GJB4 protein was brown-yellow granular in pancreatic cancer tissues, mainly expressed in cytoplasm and cell membrane, and GJB4 protein expression was up-regulated in pancreatic cancer （P < 0.05）. The RT-qPCR test results showed that out of 4 pancreatic cancer cell lines, 3 of them had upregulated expression （P < 0.05）. COX regression analysis showed that GJB4 gene was an independent risk factor in the prognosis of pancreatic cancer patients. The results of GO enrichment analysis showed that GJB4 was related to the transmembrane transport, ion channel, signal release and membrane potential regulation of pancreatic cancer. GSEA analysis showed that GJB4 was enriched in the Wnt/β-catenin signaling pathway. Conclusion In pancreatic cancer, the high expression level of GJB4 is closely related to the clinicopathological features of the patients, which may predict the poor prognosis of the patients. GJB4 may be involved in regulating the Wnt/β-catenin signaling pathway of pancreatic cancer, and is expected to be one of the potential biomarkers of pancreatic cancer prognosis.
- Pancreatic cancer,
- GJB4,
- Clinicopathological features,
- Prognosis,
- Biomarkers

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References(25)

References

[1]	Bray F,Ferlay J,Soerjomataram I,et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2018,68(6):394-424. doi: 10.3322/caac.21492
[2]	Siegel R L,Miller K D,Wagle N S,et al. Cancer statistics,2023[J]. CA-Cancer J Clin,2023,73(1):17-48. doi: 10.3322/caac.21763
[3]	Xia C,Dong X,Li H,et al. Cancer statistics in China and United States,2022: Profiles,trends,and determinants[J]. Chinese Med J-Peking,2022,135(5):584-590. doi: 10.1097/CM9.0000000000002108
[4]	Ushio J,Kanno A,Ikeda E,et al. Pancreatic ductal adenocarcinoma: Epidemiology and risk factors[J]. Diagnostics (Basel),2021,11(3):562. doi: 10.3390/diagnostics11030562
[5]	Hue J J,Sugumar K,Markt S C,et al. Facility volume-survival relationship in patients with early-stage pancreatic adenocarcinoma treated with neoadjuvant chemotherapy followed by pancreatoduodenectomys[J]. Surgery,2021,170(1):207-214. doi: 10.1016/j.surg.2020.12.003
[6]	冯永,贺定华,夏昆,等. 角皮病致病基因GJB4在遗传性耳聋中的研究[J]. 中华耳科学杂志,2005,3(4):260-262.
[7]	Dai S,Wang H,Lin Z,et al. Novel and recurrent mutations in GJB3 and GJB4 cause erythrokeratodermia variabilis et progressiva[J]. Indian Journal of Dermatology,2020,86(1):87-90.
[8]	Kokotas H,Papagiannaki K,Grigoriadou M,et al. Erythrokeratodermia variabilis: Report of two cases and a novel missense variant in GJB4 encoding connexin 30.3[J]. Eur J Dermatol,2012,22(2):182-186. doi: 10.1684/ejd.2011.1617
[9]	Consortium G. The genotype-tissue expression (GTEx) project[J]. Nature Genetics,2013,45(6):580-585. doi: 10.1038/ng.2653
[10]	Weinstein J N,Collisson E A,Mills G B,et al. The cancer genome atlas pan-cancer analysis project[J]. Nature Genetics,2013,45(10):1113-1120. doi: 10.1038/ng.2764
[11]	Zhao K,Si Y,Sun L,. et al. Efficacy and toxicity of re-irradiation for esophageal cancer patients with locoregional recurrence: A retrospective analysis[J]. Radiation Oncology,2020,15(1):243. doi: 10.1186/s13014-020-01685-2
[12]	Kampf C. A Human protein atlas[J]. Journal of Proteomics & Bioinformatics,2008,S2(1):45-46.
[13]	El-Sabban M E,Pauli B U. Cytoplasmic dye transfer between metastatic tumor cells and vascular endothelium[J]. J Cell Biol,1991,115(5):1375-1382. doi: 10.1083/jcb.115.5.1375
[14]	张孟岳,赵东强. 间隙连接蛋白家族在癌症中作用及其机制的研究进展[J]. 中国病理生理杂志,2023,39(4):747-754.
[15]	张桢,田霄峰,陈杰,等. 表皮生长因子通过间隙连接蛋白调控小鼠卵母细胞成熟的研究[J]. 生殖医学杂志,2024,33(5):618-626.
[16]	Yan,Q,Feng,Z,Jiang,B,et al. Biological functions of connexins in the development of inflammatory bowel disease[J]. Scand J Gastroentero,2024,59(2):142-149. doi: 10.1080/00365521.2023.2267713
[17]	Grek C L,Rhett J M,Bruce J S,et al. Connexin 43,breast cancer tumor suppressor: Missed connections[J]. Cancer Lett,2016,374(1):117-126. doi: 10.1016/j.canlet.2016.02.008
[18]	Lin Y P,Wu J I,Tseng C W,et al. Gjb4 serves as a novel biomarker for lung cancer and promotes metastasis and chemoresistance via Src activation[J]. Oncogene,2019,38(6):822-837. doi: 10.1038/s41388-018-0471-1
[19]	Liu G Y ,Pang Y ,Zhang Y J ,et al. GJB4 promotes gastric cancer cell proliferation and migration via Wnt/CTNNB1 pathway[J]. Ott Vol,2019,12(2): 6745–6755.
[20]	黄孝彬,谢梦忆,刘星宇,等. CTNND1通过Wnt/β-catenin信号通路调控胰腺癌细胞增殖、迁移和侵袭[J]. 现代肿瘤医学,2024,32(5):818-825.
[21]	Parsons M J,Tammela T,Dow L E. WNT as a driver and dependency in cancer[J]. Cancer Discov,2021,11(10):2413-2429. doi: 10.1158/2159-8290.CD-21-0190
[22]	张鹏,陈昆,宋登辉,等. 麦冬皂苷介导Wnt/β-catenin通路对大鼠肝部分切除后肝再生的影响[J]. 中华实用诊断与治疗杂志,2024,38(6):552-556.
[23]	Alganatay,C,Balbasi,E,Tuncbag,N,et al. SETD3 regulates endoderm differentiation of mouse embryonic stem cells through canonical Wnt signaling pathway[J]. Faseb J,2024,38(4):e23463. doi: 10.1096/fj.202301883R
[24]	陈小丽,田小容,黄晓东,等. 肿瘤抑制基因7L通过Wnt/β-catenin信号通路抑制胰腺癌细胞生长的作用机制[J]. 临床内科杂志,2024,41(2):116-119.
[25]	陈影,庄蕾,张丹红,等. 低氧微环境通过TGFBI调控Wnt/β-catenin通路介导胰腺癌化疗耐药及机制研究[J]. 现代肿瘤医学,2024,32(1):42-46.

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