The expressions and clinical significance of NF-κBp65 and autophagy related proteins Beclin1 and p62 in thyroid papillary carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LU Bin , ZHANG Peng , ZHANG Yantao ,  ZHANG Qiwen

Department of Thyroid and Breast Surgery, Jinan People's Hospital, Jinan 271100, P. R. China;

Corresponding?author：

ZHANG Qiwen, Email: lwzqw@126.com

Keywords：

thyroid cancer; lymph node metastasis; NF-κBp65; autophagy; Beclin1 protein; p62 protein

DOI：

10.7507/1007-9424.201906051

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Objective To analyze the expression and significance of NF-κBp65 and autophagy-related proteins Beclin1 and p62 in patients with papillary thyroid carcinoma (PTC).Methods One hundred and sixty cases of PTC patients' tumor tissue specimens and paracancerous tissue specimens in our hospital from March 2013 to February 2015 were collected, and 90 cases of cervical lymph node metastasis tissue specimens of the above patients were collected. The expressions of NF-κBp65, Beclin1 and p62 in PTC tissues, metastatic lymph node tissues and paracancerous tissues were detected by immunohistochemical method, and the relationship between the above indexes and the clinicopathological characteristics and prognosis of PTC patients was analyzed.Results The positive rates of expression of NF-kappa Bp65 and p62 in PTC tissues and metastatic lymph node tissues were higher than those in paracancerous tissues (P<0.05). The expression rate of Beclin1 in PTC tissues and metastatic lymph node tissues was lower than that in paracancerous tissues (P<0.05). The positive rate of NF-κBp65 expression in PTC tissues was not related to the clinicopathological characteristics of patients (P>0.05). The expression of p62 decreased with the increase of tumor differentiation (P<0.05). The expression of Beclin1 in patients with stage Ⅲ+Ⅳ and lymph node metastasis were lower than those in patients with stage Ⅰ+Ⅱ and without lymph node metastasis (P<0.05), while the expression of p62 was opposite. Spearman correlation analysis showed that the expression of Beclin1 and p62 in PTC tissues was negatively correlated (r=–0.656, P<0.01). In metastatic lymph node tissues, the expression of Beclin1 and p62 was also negatively correlated (r=–0.562, P<0.01). The 3-year survival rates of patients with positive expression of p62 and NF-κBp65 in PTC tissues were lower than that of patients with negative expression (P<0.05). The 3-year survival rate of patients with positive expression of Becrin1 was higher than that of negative expression (P<0.05). TNM stage, lymph node metastasis, NF-κBp65 and p62 were independent risk factors for PTC prognosis, and Beclin1 was protective factor.Conclusions NF-κBp65 and p62 are highly expressed in PTC tissues and lymph node metastasis tissues, while Beclin1 is poorly expressed, which could be used as independent prognostic factors for PTC patients. In addition, Beclin1 and p62 are related to PTC biological behavior and may become potential indicators for PTC diagnosis.

Citation： LU Bin, ZHANG Peng, ZHANG Yantao, ZHANG Qiwen. The expressions and clinical significance of NF-κBp65 and autophagy related proteins Beclin1 and p62 in thyroid papillary carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(11): 1304-1310. doi: 10.7507/1007-9424.201906051 Copy

1.	劉文, 程若川. 甲狀腺乳頭狀癌中央區淋巴結轉移的預測因素. 中國普外基礎與臨床雜志, 2018, 25(1): 99-103.
2.	范曉峰, 李曉東, 周冬. 低位弧形切口法與" L”型切口法在甲狀腺癌合并頸部淋巴結轉移患者手術中的應用. 醫學臨床研究, 2016, 33(5): 916-918.
3.	Vegliante R, Desideri E, Di Leo L, et al. Dehydroepiandrosterone triggers autophagic cell death in human hepatoma cell line HepG2 via JNK-mediated p62/SQSTM1 expression. Carcinogenesis, 2016, 37(3): 233-244.
4.	劉美快, 袁哲英, 黃凱西, 等. 低強度超聲聯合微泡通過提高 ROS 水平促進甲狀腺癌細胞自噬性死亡. 中國病理生理雜志, 2017, 33(11): 2000-2008.
5.	Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol, 2018, 18(5): 309-324.
6.	Liu B, Sun L, Liu Q, et al. A cytoplasmic NF-κB interacting long noncoding RNA blocks IκB phosphorylation and suppresses breast cancer metastasis. Cancer cell, 2015, 27(3): 370-381.
7.	鄭向前, 林琳, 夏婷婷, 等. 美國甲狀腺學會 2009 年分化型甲狀腺癌診治指南解讀. 中華普通外科雜志, 2011, 26(4): 349-352.
8.	王曉蔚, 康凱夫. Beclin1 和 NF-κBp65 表達與肝癌發生發展的相關性研究. 中華腫瘤防治雜志, 2009, 16(13): 974-977.
9.	李田軍, 林巖松, 梁軍, 等. 分化型甲狀腺癌相關基因的研究進展. 中華腫瘤防治雜志, 2011, 18(11): 896-900.
10.	Ahn S, Kim TH, Kim SW, et al. Comprehensive screening for PD-L1 expression in thyroid cancer. Endocr-Relat Cancer, 2017, 24(2): 97-106.
11.	TKim EJ, Jeong JH, Bae S, et al. mTOR inhibitors radiosensitize PTEN-deficient non-small-cell lung cancer cells harboring an EGFR activating mutation by inducing autophagy. J Cell Biochem, 2013, 114(6): 1248-1256.
12.	韓穎, 吳正升, 吳強. 乳腺癌新輔助化療前后 p62 和XIAP表達的變化及其意義. 臨床與實驗病理學雜志, 2017, 33(5): 481-484.
13.	Dong S, Qu X, Li W, et al. The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression. J Hematol Oncol, 2015, 8(1): 43.
14.	Rohatgi RA, Janusis J, Leonard D, et al. Beclin 1 regulates growth factor receptor signaling in breast cancer. Oncogene, 2015, 34(42): 5352-5362.
15.	Chang MA, Morgado M, Warren CR, et al. p62/SQSTM1 is required for cell survival of apoptosis-resistant bone metastatic prostate cancer cell lines. Prostate, 2014, 74(2): 149-163.
16.	謝昆, 李密杰, 蔣成硯, 等. 自噬相關蛋白 ATG5/BECLIN-1 調控細胞自噬和凋亡的分子機理研究進展. 中國人獸共患病學報, 2018, 34(3): 272-275.
17.	侯德法. 胃癌組織中 LC3B 和 p62 的表達和臨床意義. 安徽醫藥, 2017, 21(9): 1647-1650.
18.	Yu T, Guo F, Yu Y, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell, 2017, 170(3): 548-563.
19.	王幼輝, 王錫恩, 彭敏, 等. 自噬相關蛋白 Beclin1、p62、Atg5 在漿液性卵巢癌組織中的表達及臨床意義. 中華內分泌外科雜志, 2016, 10(4): 329-332.
20.	Camargo R, Riccardi D, Ribeiro H, et al. NF-κBp65 and expression of its pro-inflammatory target genes are upregulated in the subcutaneous adipose tissue of cachectic cancer patients. Nutrients, 2015, 7(6): 4465-4479.
21.	Kang K F, Wang X W, Chen X W, et al. Beclin 1 and nuclear factor-κBp65 are upregulated in hepatocellular carcinoma. Oncology Letters, 2013, 5(6): 1813-1818.
22.	廖桂周. NIBP 和 NF-κBp65 在胃癌中的表達及其臨床意義. 中國醫藥科學, 2016, 6(14): 27-30.
23.	Guo YZ, He P, Feng AM. Effect of curcumin on expressions of NF-κ Bp65,TNF-α and IL-8 in placental tissue of premature birth of infected mice. Asian Pac J Trop Med, 2017, 10(2): 168-171.
24.	Zhu J, Yang L, Chen C, et al. NF-κB p65 overexpression promotes bladder cancer cell migration via FBW7-mediated degradation of RhoGDIα protein. Neoplasia, 2017, 19(9): 672-683.

1. 劉文, 程若川. 甲狀腺乳頭狀癌中央區淋巴結轉移的預測因素. 中國普外基礎與臨床雜志, 2018, 25(1): 99-103.
2. 范曉峰, 李曉東, 周冬. 低位弧形切口法與" L”型切口法在甲狀腺癌合并頸部淋巴結轉移患者手術中的應用. 醫學臨床研究, 2016, 33(5): 916-918.
3. Vegliante R, Desideri E, Di Leo L, et al. Dehydroepiandrosterone triggers autophagic cell death in human hepatoma cell line HepG2 via JNK-mediated p62/SQSTM1 expression. Carcinogenesis, 2016, 37(3): 233-244.
4. 劉美快, 袁哲英, 黃凱西, 等. 低強度超聲聯合微泡通過提高 ROS 水平促進甲狀腺癌細胞自噬性死亡. 中國病理生理雜志, 2017, 33(11): 2000-2008.
5. Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol, 2018, 18(5): 309-324.
6. Liu B, Sun L, Liu Q, et al. A cytoplasmic NF-κB interacting long noncoding RNA blocks IκB phosphorylation and suppresses breast cancer metastasis. Cancer cell, 2015, 27(3): 370-381.
7. 鄭向前, 林琳, 夏婷婷, 等. 美國甲狀腺學會 2009 年分化型甲狀腺癌診治指南解讀. 中華普通外科雜志, 2011, 26(4): 349-352.
8. 王曉蔚, 康凱夫. Beclin1 和 NF-κBp65 表達與肝癌發生發展的相關性研究. 中華腫瘤防治雜志, 2009, 16(13): 974-977.
9. 李田軍, 林巖松, 梁軍, 等. 分化型甲狀腺癌相關基因的研究進展. 中華腫瘤防治雜志, 2011, 18(11): 896-900.
10. Ahn S, Kim TH, Kim SW, et al. Comprehensive screening for PD-L1 expression in thyroid cancer. Endocr-Relat Cancer, 2017, 24(2): 97-106.
11. TKim EJ, Jeong JH, Bae S, et al. mTOR inhibitors radiosensitize PTEN-deficient non-small-cell lung cancer cells harboring an EGFR activating mutation by inducing autophagy. J Cell Biochem, 2013, 114(6): 1248-1256.
12. 韓穎, 吳正升, 吳強. 乳腺癌新輔助化療前后 p62 和XIAP表達的變化及其意義. 臨床與實驗病理學雜志, 2017, 33(5): 481-484.
13. Dong S, Qu X, Li W, et al. The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression. J Hematol Oncol, 2015, 8(1): 43.
14. Rohatgi RA, Janusis J, Leonard D, et al. Beclin 1 regulates growth factor receptor signaling in breast cancer. Oncogene, 2015, 34(42): 5352-5362.
15. Chang MA, Morgado M, Warren CR, et al. p62/SQSTM1 is required for cell survival of apoptosis-resistant bone metastatic prostate cancer cell lines. Prostate, 2014, 74(2): 149-163.
16. 謝昆, 李密杰, 蔣成硯, 等. 自噬相關蛋白 ATG5/BECLIN-1 調控細胞自噬和凋亡的分子機理研究進展. 中國人獸共患病學報, 2018, 34(3): 272-275.
17. 侯德法. 胃癌組織中 LC3B 和 p62 的表達和臨床意義. 安徽醫藥, 2017, 21(9): 1647-1650.
18. Yu T, Guo F, Yu Y, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell, 2017, 170(3): 548-563.
19. 王幼輝, 王錫恩, 彭敏, 等. 自噬相關蛋白 Beclin1、p62、Atg5 在漿液性卵巢癌組織中的表達及臨床意義. 中華內分泌外科雜志, 2016, 10(4): 329-332.
20. Camargo R, Riccardi D, Ribeiro H, et al. NF-κBp65 and expression of its pro-inflammatory target genes are upregulated in the subcutaneous adipose tissue of cachectic cancer patients. Nutrients, 2015, 7(6): 4465-4479.
21. Kang K F, Wang X W, Chen X W, et al. Beclin 1 and nuclear factor-κBp65 are upregulated in hepatocellular carcinoma. Oncology Letters, 2013, 5(6): 1813-1818.
22. 廖桂周. NIBP 和 NF-κBp65 在胃癌中的表達及其臨床意義. 中國醫藥科學, 2016, 6(14): 27-30.
23. Guo YZ, He P, Feng AM. Effect of curcumin on expressions of NF-κ Bp65,TNF-α and IL-8 in placental tissue of premature birth of infected mice. Asian Pac J Trop Med, 2017, 10(2): 168-171.
24. Zhu J, Yang L, Chen C, et al. NF-κB p65 overexpression promotes bladder cancer cell migration via FBW7-mediated degradation of RhoGDIα protein. Neoplasia, 2017, 19(9): 672-683.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The expressions and clinical significance of NF-κBp65 and autophagy related proteins Beclin1 and p62 in thyroid papillary carcinoma

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