PINK1和Parkin在结直肠癌组织中的表达及临床价值
Expression and Clinical Significance of PINK1 and Parkin in Colorectal Cancer
DOI: 10.12677/ACM.2023.1381772, PDF,   
作者: 张顺涛, 李巧玉, 张园梦, 邱烈旺, 曾 波*:重庆医科大学附属永川医院消化内科,重庆;高敏娜:重庆医科大学病理教研室,重庆
关键词: 结直肠癌线粒体自噬PINK1ParkinColorectal Cancer Mitophagy PINK1 Parkin
摘要: 目的:监测结直肠癌组织中与线粒体自噬过程紧密相关的基因PINK1和Parkin的表达情况,并探讨其存在的临床价值。方法:应用免疫组织化学染色SP法检测肠镜检查或手术过程中获取的120例结直肠癌组织、45例结直肠腺瘤组织和45例正常结直肠组织(距肿瘤 > 5 cm)中PINK1和Parkin的表达情况,分析PINK1和Parkin之间的内在关联性以及PINK1和Parkin的表达与结直肠癌患者的性别、年龄、肿瘤体积、病理类型、分化程度、淋巴结转移、远处转移和临床TNM分期等关联性。结果:免疫组化结果表明PINK1和Parkin阳性表达均主要发生在肿瘤细胞胞浆中。120例结直肠癌组织中PINK1和Parkin阳性表达率分别为56.67% (68/120)和47.5% (57/120),明显低于肠腺瘤组织和正常肠组织中的表达(P < 0.01)。PINK1和Parkin蛋白在结直肠癌组织中的表达具有正相关性(r = 0.5528, P < 0.05)。在结直肠癌组织中,PINK1和Parkin的阳性表达与其分化程度、淋巴结转移、远处转移和临床TNM分期具有明显的关联性(P < 0.05);而与患者年龄、性别、肿瘤体积、病理类型无关(P > 0.05)。结论:PINK1和Parkin在结直肠癌组织中呈现低水平表达状态,提示线粒体自噬活性的降低在结直肠癌的发生发展和侵袭转移中可能发挥了一定作用。
Abstract: Objective: To observe the expression of PINK1 and Parkin closely related to mitochondrial autoph-agy in colorectal cancerandn and to explore the clinical significance. Methods: Immunohistochemi-cal SP methods was applied to detect the expressions of PINK1 and Parkin in 120 colorectal cancer tissues, 45 intestinal adenoma tissues and 45 normal intestinal tissues (5 cm away from the cancer). The correlation between PINK1 and Parkin was analyzed; while, the relationships between the ex-pression of PINK1, Parkin and the clinicopathological features, including sex, age, size, pathological type, differentiation degress, lymph node metastasis, distant organs metastasis and TNM stage were analyzed. Results: Immunohistochemical results showed that the positive expressions of PINK1 and Parkin were mainly located in the cytoplasm of the cells, and their positive expression rates in 120 colorectal cancer tissues were 56.67% (68/120) and 47.5% (57/120), respectively, which were both significantly lower than those in intestinal adenoma tissues and normal intestinal tissues (P < 0.01). There was a positive correlation between the expression of PINK1 and Parkin in colorectal cancer (r = 0.5528, P < 0.05). In colorectal cancer, the positive expression of PINK1 and Parkin was significantly correlated with the degree of differentiation, distant organ metastasis, lymph node metastasis and TNM stage (P < 0.05); and they were both independent to age, sex, tumor size and pathological type (P > 0.05). Conclusion: PINK1 and Parkin were low expressed in colorectal cancer, which suggested that the decrease of the mitophagy activity may play a role in the occurrence, de-velopment, invasion and metastasis of colorectal cancer.
文章引用:张顺涛, 李巧玉, 张园梦, 邱烈旺, 高敏娜, 曾波. PINK1和Parkin在结直肠癌组织中的表达及临床价值[J]. 临床医学进展, 2023, 13(8): 12639-12645. https://doi.org/10.12677/ACM.2023.1381772

参考文献

[1] Dilly, A., Honick, B.D., Lee, Y.J., et al. (2020) Rational Application of Targeted Therapeutics in Mucinous Co-lon/Appendix Cancers with Positive Predictive Factors. Cancer Medicine, 9, 1753-1767. [Google Scholar] [CrossRef] [PubMed]
[2] Rabanalruiz, Y., Otten, E.G. and Korolchuk, V.I. (2017) mTORC1 as the Main Gateway to Autophagy. Essays in Biochemistry, 61, 565-584. [Google Scholar] [CrossRef
[3] Wang, X., Li, H., Li, W., et al. (2020) The Role of Caspa-se-1/GSDMD-Mediated Pyroptosis in Taxol-Induced Cell Death and a Taxol-Resistant Phenotype in Nasopharyngeal Carcinoma Regulated by Autophagy. Cell Biology and Toxicology, 36, 437-457. [Google Scholar] [CrossRef] [PubMed]
[4] Zhang, L., Liu, X., Song, L., Zhai, H. and Chang, C. (2020) MAP7 Promotes Migration and Invasion and Progression of Human Cervical Cancer Through Modulating the Autoph-agy. Cancer Cell International, 20, Article No. 17. [Google Scholar] [CrossRef] [PubMed]
[5] Chu, Y., Wang, Y., Li, K., et al. (2020) Human Omental Adi-pose-Derived Mesenchymal Stem Cells Enhance Autophagy in Ovarian Carcinoma Cells through the STAT3 Signalling Pathway. Cellular Signalling, 24, Article ID: 109549. [Google Scholar] [CrossRef] [PubMed]
[6] Shefa, U., Jeong, N.Y., Song, I.O., Chung, H.J., Kim, D., Jung, J. and Huh, Y. (2019) Mitophagy Links Oxidative Stress Conditions and Neurodegenerative Diseases. Neural Regenera-tion Research, 14, 749-756. [Google Scholar] [CrossRef] [PubMed]
[7] Zhong, Z.Y., Sanchez-Lopez, E. and Karin, M. (2016) Autophagy, Inflammation, and Immunity: A Troika Governing Cancer and Its Treatment. Cell, 166, 288-298. [Google Scholar] [CrossRef] [PubMed]
[8] Di Rita, A., Peschiaroli, A., D’Acunzo, P., et al. (., 2018) HUWE1 E3 Ligase Promotes PINK1/PARKIN-Independent Mitophagy by Regulating AMBRA1 Activation via IKKalpha. Na-ture Communications, 9, Article No. 3755. [Google Scholar] [CrossRef] [PubMed]
[9] Kong, H., Jiang, C.-Y., Hu, L., et al. (2019) Morphine Induces Dysfunction of PINK1/Parkin-Mediated Mitophagy in Spinal Cord Neurons Implying Involvement in Antinociceptive Tolerance. Journal of Molecular Cell Biology, 11, 1056-1068. [Google Scholar] [CrossRef] [PubMed]
[10] Palikaras, K., Lionaki, E. and Tavernarakis, N. (2018) Mechanisms of Mitophagy in Cellular Homeostasis, Physiology and Pathology. Nature Cell Biology, 20, 1013-1022. [Google Scholar] [CrossRef] [PubMed]
[11] Salazar, C., Ruiz-Hincapie, P. and Ruiz, L.M. (2018) The Inter-play among PINK1/PARKIN/Dj-1 Network during Mitochondrial Quality Control in Cancer Biology: Protein Interaction Analysis. Cell, 7, Article No. 154. [Google Scholar] [CrossRef] [PubMed]
[12] Lazarou, M., Sliter, D.A., Kane, L.A., et al. (2015) The Ubiquitin Kinase PINK1 Recruits Autophagy Receptors to Induce Mitophagy. Nature, 524, 309-314. [Google Scholar] [CrossRef] [PubMed]
[13] Boyle, K.A., Van Wickle, J., Hill, R.B., et al. (2018) Mitochon-dria-Targeted Drugs Stimulate Mitophagy and Abrogate Colon Cancer Cell Proliferation. Journal of Biological Chemistry, 293, 14891-14904. [Google Scholar] [CrossRef
[14] Han, J., Zhang, J., Zhang, W., et al. (2019) Abiraterone and MDV3100 Inhibits the Proliferation and Promotes the Apoptosis of Prostate Cancer Cells through Mitophagy. Cancer Cell International, 19, Article No. 332. [Google Scholar] [CrossRef] [PubMed]
[15] Gladkova, C., Maslen, S.L., Skehel, J.M. and Komander, D. (2018) Mechanism of Parkin Activation by PINK1. Nature, 559, 410-414. [Google Scholar] [CrossRef] [PubMed]
[16] Bernardini, J.P., Lazarou, M. and Dewson, G. (2017) Parkin and Mitophagy in Cancer. Oncogene, 36, 1315-1327. [Google Scholar] [CrossRef] [PubMed]
[17] 丁高峰, 郭雷鸣, 柯少瑞, 陆寓非. 腮腺多形性腺瘤及癌在多形性腺瘤中PINK1和Parkin的表达及临床意义[J]. 肿瘤防治研究, 2021, 48(5): 470-473.
[18] Jeong, S.M., Hwang, S., Park, K., Yang, S. and Seong, R.H. (2016) Enhanced Mitochondrial Glutamine Anaplerosis Suppresses Pancreatic Can-cer Growth through Autophagy Inhibition. Scientific Reports, 6, Article No. 30767. [Google Scholar] [CrossRef] [PubMed]