Expression of ALG2 in oral squamous cell carcinoma and its prognostic diagnostic value

doi:10.12439/kqhm.1005-4979.2024.05.005

Abstract

Abstract: Objective: To analyze the expression of apoptosis-linked gene-2 (ALG2) in oral squamous cell carcinoma (OSCC) tissues and cell lines and its correlations with the clinicopathological features and prognosis of patients. Methods: The expression of ALG2 in 5 pairs of fresh OSCC tissues, paracancerous normal tissues, OSCC cell lines and human oral keratinocytes (HOK) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expression levels of ALG2 in paraffin-embedded OSCC tissues and adjacent normal tissues specimens of 128 patients with OSCC were detected by immunohistochemistry (IHC). The correlation of ALG2 expression in OSCC tissues with the clinicopathological features and survival time of patients were analyzed. The expression of ALG2 in OSCC tissues and its diagnostic, prognostic value were detected in TCGA database. Results: The expression of ALG2 in OSCC tissues and cell lines was significantly higher than those in paracancerous tissues and HOK cells (P<0.05). The overall survival, disease free survival and progression-free survival of OSCC patients in the group with low ALG2 expression were significantly higher than those in the ALG2 high expression group (P<0.05). T stage, lymphatic metastasis, and ALG2 expression were all factors affecting the prognosis of OSCC patients (P<0.05). ALG2 expression was an independent predictor of the prognosis of OSCC patients (P<0.01). ALG2 may have some diagnostic value for OSCC [area under the curve (AUC)=0.807]. Conclusion: ALG2 is highly expressed in OSCC and it is associated with unfavorable prognosis of the patients, and it may have some diagnostic value for OSCC.

Key words: oral squamous cell carcinoma, apoptosis-linked gene-2, prognosis

摘要：

目的：分析凋亡关联基因 2（apoptosis-linked gene-2，ALG2）在口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）组织中的表达及其与临床病理特征的相关性、预后诊断价值。方法：实时定量聚合酶链反应（real-time quantitative polymerase chain reaction，RT-qPCR) 检测 ALG2 在 5 对新鲜 OSCC 组织、癌旁组织及 OSCC 细胞系、人口腔黏膜角质形成细胞（human oral keratinocytes，HOK）中的表达；免疫组织化学（immunohistochemistry，IHC）法检测ALG2 在 128 对 OSCC 组织和癌旁组织中的表达，并分析其表达高低与临床病理特征及预后的相关性；利用 TCGA 数据库分析 ALG2 在 OSCC 组织中的表达及其预后诊断价值。结果：ALG2 在 OSCC 组织和细胞系中的表达明显高于其在癌旁组织和 HOK 细胞中（P<0.05）；ALG2 低表达组 OSCC 患者的总体生存率、无疾病生存率和无进展生存率均显著高于 ALG2 高表达组（P<0.05）；T 分期、淋巴结转移、ALG2 表达水平均是影响 OSCC 患者预后的因素（P<0.05），且ALG2 表达是 OSCC 患者预后的一个独立预测因素（P<0.01）；ALG2 对 OSCC 可能具有一定的诊断价值 [ 曲线下面积（area under the curve，AUC）=0.807]。结论：ALG2 在 OSCC 中高表达，且与患者预后不良有关，对 OSCC 可能具有一定的诊断价值。

关键词: 口腔鳞状细胞癌, 凋亡关联基因 2, 预后

CLC Number:

R739.8
R782

GAO Rui, GUO Lei, PENG Bo, JIA Jun.

Expression of ALG2 in oral squamous cell carcinoma and its prognostic diagnostic value

[J]. 《Journal of Oral and Maxillofacial Surgery》, 2024, 34(5): 357-364.

高瑞, 郭磊, 彭博, 贾骏.

ALG2在口腔鳞状细胞癌中的表达及其预后诊断价值

[J]. 《口腔颌面外科杂志》, 2024, 34(5): 357-364.

/ / Recommend / Download Citations

URL: https://journal06.magtech.org.cn/Jweb_joms/EN/10.12439/kqhm.1005-4979.2024.05.005

https://journal06.magtech.org.cn/Jweb_joms/EN/Y2024/V34/I5/357

References

[1] Ng JH, Iyer NG, Tan MH, et al. Changing epidemiology of oral squamous cell carcinoma of the tongue: A global study[J]. Head Neck, 2017, 39(2): 297-304.
[2] Warnakulasuriya S, Kerr AR. Oral cancer screening: Past, present, and future[J]. J Dent Res, 2021, 100(12): 1313-1320.
[3] Gharat SA, Momin M, Bhavsar C. Oral squamous cell carcinoma: Current treatment strategies and nanotechnology-based approaches for prevention and therapy[J]. Crit Rev Ther Drug Carrier Syst, 2016, 33(4): 363-400.
[4] de Morais EF, Almangush A, Salo T, et al. Emerging histopathological parameters in the prognosis of oral squamous cell carcinomas[J]. Histol Histopathol, 2024, 39(1): 1-12.
[5] Vitório JG, Duarte-Andrade FF, Dos Santos Fontes Pereira T, et al. Metabolic landscape of oral squamous cell carcinoma[J]. Metabolomics, 2020, 16(10): 105.
[6] Ji WS, Zhang LF, Xu XY, et al. ALG2 regulates type I interferon responses by inhibiting STING trafficking[J]. J Cell Sci, 2021, 134(24): jcs259060.
[7] Maki M, Takahara T, Shibata H. Multifaceted roles of ALG-2 in Ca( 2+ )-regulated membrane trafficking[J]. Int J Mol Sci, 2016, 17(9): 1401.
[8] Ji WS, Xin Y, Zhang LF, et al. ALG2 Influences T cell apoptosis by regulating FASLG intracellular transportation[J]. Biochem J, 2020, 477(16): 3105-3121.
[9] Liu SG, Yuan SH, Wu HY, et al. The programmed cell death 6 interacting protein insertion/deletion polymorphism is associated with non-small cell lung cancer risk in a Chinese Han population[J]. Tumour Biol, 2014, 35(9): 8679-8683.
[10] Su D, Xu HY, Feng JG, et al. PDCD6 is an independent predictor of progression free survival in epithelial ovarian cancer[J]. J Transl Med, 2012, 10: 31.
[11] Bugshan A, Farooq I. Oral squamous cell carcinoma: Metastasis, potentially associated malignant disorders, etiology and recent advancements in diagnosis[J]. F1000Res, 2020, 9: 229.
[12] Wang WL, Adeoye J, Thomson P, et al. Statistical profiling of oral cancer and the prediction of outcome[J]. J Oral Pathol Med, 2021, 50(1): 39-46.
[13] Fujima N, Andreu-Arasa VC, Meibom SK, et al. Deep learning analysis using FDG-PET to predict treatment outcome in patients with oral cavity squamous cell carcinoma[J]. Eur Radiol, 2020, 30(11): 6322-6330.
[14] Creff G, Jegoux F, Palard X, et al. 18F-FDG PET/CT-based prognostic survival model after surgery for head and neck cancer[J]. J Nucl Med, 2022, 63(9): 1378-1385.
[15] Panarese I, Aquino G, Ronchi A, et al. Oral and Oropharyngeal squamous cell carcinoma: Prognostic and predictive parameters in the etiopathogenetic route[J]. Expert Rev Anticancer Ther, 2019, 19(2): 105-119.
[16] Maki M. Structures and functions of penta-EF-hand calcium-binding proteins and their interacting partners: Enigmatic relationships between ALG-2 and calpain-7[J]. Biosci Biotechnol Biochem, 2020, 84(4): 651-660.
[17] Loers G, Theis T, Baixia Hao H, et al. Interplay in neural functions of cell adhesion molecule close homolog of L1 (CHL1) and Programmed Cell Death 6 (PDCD6)[J]. FASEB Bioadv, 2022, 4(1): 43-59.
[18] Shibata H. Adaptor functions of the Ca2+-binding protein ALG-2 in protein transport from the endoplasmic reticulum[J]. Biosci Biotechnol Biochem, 2019, 83(1): 20-32.
[19] Sasazawa Y, Souma S, Furuya N, et al. Oxidative stress-induced phosphorylation of JIP4 regulates lysosomal positioning in coordination with TRPML1 and ALG2[J]. EMBO J, 2022, 41(22): e111476.
[20] Shih LC, He JL, Chang WS, et al. The contribution of PDCD6 polymorphisms to oral cancer risk[J]. Cancer Genomics Proteomics, 2022, 19(4): 456-463.
[21] Qin J, Li DW, Zhou YQ, et al. Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton[J]. Oncotarget, 2017, 8(2): 2745-2757.
[22] Zhang DK, Wang F, Pang Y, et al. ALG2 regulates glioblastoma cell proliferation, migration and tumorigenicity[J]. Biochem Biophys Res Commun, 2017, 486(2): 300-306.
[23] Wang XJ, Wu F, Wang H, et al. PDCD6 cooperates with CRaf to facilitate colorectal cancer progression via Raf/MEK/ERK activation[J]. J Exp Clin Cancer Res, 2020, 39(1): 147.
[24] la Cour JM, Høj BR, Mollerup J, et al. The apoptosis linked gene ALG-2 is dysregulated in tumors of various origin and contributes to cancer cell viability[J]. Mol Oncol, 2008, 1(4): 431-439.
[25] Zhu GM, Xia HW, Tang QL, et al. An epithelial-mesenchymal transition-related 5-gene signature predicting the prognosis of hepatocellular carcinoma patients[J]. Cancer Cell Int, 2021, 21(1): 166.

Please choose a citation manager

Content to export