[1]席 恺,张苗苗,张 曦,等.喉鳞状细胞癌组织中ATF6 和IFN-α 的表达与临床病理特征及预后的相关性研究[J].现代检验医学杂志,2024,39(02):12-17.[doi:10.3969/j.issn.1671-7414.2024.02.003]
　XI Kai,ZHANG Miaomiao,ZHANG Xi,et al.Correlation of ATF6 and IFN-α Expression with Clinicopathological Features and Prognosis in Laryngeal Squamous Cell Carcinoma[J].Journal of Modern Laboratory Medicine,2024,39(02):12-17.[doi:10.3969/j.issn.1671-7414.2024.02.003]
点击复制

喉鳞状细胞癌组织中ATF6 和IFN-α 的表达与临床病理特征及预后的相关性研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年02期
页码:
12-17
栏目:
论著
出版日期:
2024-03-31

文章信息/Info

Title:
Correlation of ATF6 and IFN-α Expression with Clinicopathological Features and Prognosis in Laryngeal Squamous Cell Carcinoma
文章编号:
1671-7414（2024）02-012-06
作者:
席 恺 ; 张苗苗; 张 曦; 张腾腾; 邢丙文
（河南科技大学临床医学院/ 河南科技大学第一附属医院耳鼻喉科，河南洛阳 471003）
Author(s):
XI Kai;  ZHANG Miaomiao;  ZHANG Xi;  ZHANG Tengteng;  XING Bingwen
（Department of Otolaryngology, Clinical Medical College of Henan University of Science and Technology / the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan Luoyang, 471003, China）
关键词:
喉鳞状细胞癌; 转录激活因子6; 干扰素α; 淋巴结转移; 浸润深度; 内质网应激
分类号:
R739.65；R730.43
DOI:
10.3969/j.issn.1671-7414.2024.02.003
文献标志码:
A
摘要:
目的　探讨转录激活因子6（activating transcription factor 6，ATF6）和干扰素α（interferon α，IFN-α）在喉鳞状细胞癌（laryngeal squamous cell carcinoma，LSCC）组织中的表达及意义。方法　选取2015 年3 月~2020 年3 月于河南科技大学临床医学院/ 河南科技大学第一附属医院入院治疗的100 例LSCC患者，收集整理其肿瘤部位、分化程度、淋巴结转移等临床病理特征；采用免疫组织化学法检测组织中ATF6 和IFN-α 的表达；采用Spearman 法分析LSCC 组织中ATF6 与IFN-α 表达的相关性；用Kaplan-Meier 法分析LSCC 组织中ATF6，IFN-α 表达与患者三年生存率的关系；采用COX 回归分析LSCC 患者一年死亡的影响因素。结果　ATF6 在LSCC 组织中阳性率（76.00%）明显高于癌旁正常组织（13.00%），IFN-α 在LSCC 组织中阳性率（29.00%）明显低于癌旁正常组织（74.00%），差异具有统计学意义（χ2=80.352，40.536，均P ＜ 0.05）；TNM 分期为III+IV 期、浸润深度为深层、发生淋巴结转移的LSCC 患者ATF6 阳性表达比例均显著高于TNM 分期为I+II 期、浸润深度为浅层、未发生淋巴结转移的LSCC 患者（χ2=7.310，9.223，5.123，均P ＜ 0.05）。TNM 分期为III+IV 期、浸润深度为深层、发生淋巴结转移的LSCC 患者IFN-α 阴性表达比例均显著高于TNM 分期为I+II 期、浸润深度为浅层、未发生淋巴结转移的LSCC 患者（χ2=8.564，5.021，5.203，均P ＜ 0.05）；LSCC 组织中ATF6 与IFN-α 表达具有负相关性（r=-0.415，P ＜ 0.05）；ATF6 阳性表达组LSCC 患者三年生存率（50.00%）显著低于ATF6 阴性表达组（83.33%），IFN-α 阳性表达组LSCC 患者三年生存率（82.76%）显著高于IFN-α 阴性表达组（47.89%）（Log rank χ2=8.002，10.854，均P＜ 0.05）。ATF6（HR=1.735，95%CI：1.159~2.598），IFN-α（HR=0.624，95%CI：0.439~0.886）均是LSCC 患者死亡的影响因素（P ＜ 0.05）。结论　LSCC 组织中ATF6阳性表达率升高、IFN-α 阳性表达率下降，均与患者临床病理特征及预后密切相关。
Abstract:
Objective　To investigate the expression of activating transcription factor 6 (ATF6) and interferon α (IFN-α) and their significance in laryngeal squamous cell carcinoma (LSCC) tissue. Methods　A total of 100 LSCC patients admitted to Clinical Medical College of Henan University of Science and Technology/the First Affiliated Hospital of Henan University of Science and Technology from March 2015 to March 2020 were selected, and their clinicopathological features such as tumor location, degree of differentiation, and lymph node metastasis were collected and organized. Immunohistochemical method was applied to detect the expression of ATF6 and IFN-α in tissues. Spearman method was used to analyze the correlation between ATF6 and IFN-α expression in LSCC tissue. Kaplan-Meier method was applied to analyze the relationship between ATF6 and IFN-α expression in LSCC tissue and 3-year survival rate of patients. Cox regression was used to analyze the influencing factors of 3-year mortality in LSCC patients. Results　The positive rate of ATF6 in LSCC tissue (76.00%) was higher than that in normal tissues adjacent to cancer (13.00%), the positive rate of IFN-α in LSCC tissue (29.00%) was lower than that in normal tissues adjacent to cancer (74.00%), and the difference was statistically significant (χ2=80.352, 40.536, all P<0.05). The proportions of ATF6 positive expression in LSCC patients with TNM stage III+IV, deep infiltration depth, and lymph node metastasis were significantly higher than those in LSCC patients with TNM stage I+II, shallow infiltration depth, and no lymph node metastasis (χ2=7.310, 9.223, 5.123, all P ＜ 0.05). The proportions of IFN-α negative expression in LSCC patients with TNM stage III+IV, deep infiltration depth, and lymph node metastasis were significantly higher than those in LSCC patients with TNM stage I+II, shallow infiltration depth, and no lymph node metastasis (χ2=8.564, 5.021, 5.203, all P ＜ 0.05). There was a negative correlation between ATF6 and IFN-α expression in LSCC tissues (r=-0.415, P<0.05). The 3-year survival rate of LSCC patients in the ATF6 positive expression group (50.00%) was significantly lower than that in the ATF6 negative expression group (83.33%), while the 3-year survival rate of LSCC patients in the IFN-α positive expression group (82.76%) was significantly higher than that in the IFN-α negative expression group (47.89%) (Log rank χ2=8.002, 10.854, all P<0.05). ATF6 (HR=1.735, 95%CI: 1.159~2.598) and IFN-α (HR=0.624, 95%CI: 0.439~0.886) were influencing factors for the mortality of LSCC patients. Conclusion　The positive expression rate of ATF6 increased and the positive expression rate of IFN-α decreased in LSCC tissues. They were closely related to the clinical pathological characteristics and prognosis of patients.

参考文献/References:

[1] 崔力方, 曲丛玲, 赵洪禹, 等. 喉鳞状细胞癌组织HPV16 和p16 表达的临床意义[J]. 中华肿瘤防治杂志, 2021, 28(9): 661-667. CUI Lifang, QU Congling, ZHAO Hongyu, et al. Clinical significance of HPV16 and p16 expression in laryngeal squamous cell carcinoma[J]. Chinese Journal of Cancer Prevention and Treatment, 2021, 28(9): 661-667.
[2] SEEBAUER C T, HACKENBERG B, GROSSE J, et al. Routine restaging after primary non-surgical treatment of laryngeal squamous cell carcinoma-a review[J].Strahlentherapie und Onkologie, 2021, 197(3): 167-176.
[3] DUBEY P, GUPTA R, MISHRA A, et al. Evaluation of correlation between CD44, radiotherapy response,and survival rate in patients with advanced stage of head and neck squamous cell carcinoma (HNSCC)[J].Cancer Medicine, 2022, 11(9): 1937-1947.
[4] 马炜祥, 张婷婷, 崔凤针, 等. 内质网应激关键分子ATF6α 在癌症中作用的研究进展[J]. 华中科技大学学报( 医学版), 2022, 51(2)：241-246, 253. MA Weixiang, ZHANG Tingting, CUI Fengzhen,et al. Role of endoplasmic reticulum stress key molecule ATF6α in cancer development[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong(Medical Edition), 2022, 51(2): 241-246,253.
[5] BLAAUBOER A, SIDERAS K, VAN EIJCK C H J, et al. Type I interferons in pancreatic cancer and development of new therapeutic approaches[J]. Critical Reviews in Oncology Hematology, 2021, 159: 103204.
[6] GRILO A L, MANTALARIS A. Apoptosis: a mammalian cell bioprocessing perspective[J].Biotechnology Advances, 2019, 37(3): 459-475.
[7] 彭丽娜, 武川军, 冯志星, 等. IDO1 和IL-10 在喉鳞状细胞癌组织中的表达及其与临床病理特征和预后的关系研究[J]. 中国现代医学杂志, 2022, 32(1)：69-74. PENG Lina, WU Chuanjun, FENG Zhixing, et al. Expression of IDO1 and IL-10 in laryngeal squamous cell carcinoma and their relationship with clinicopathological features and prognosis[J]. China Journal of Modern Medicine, 2022, 32(1): 69-74.
[8] VAN DEN BOSCH S, CZERWINSKI M, GOVERS T,et al. Diagnostic test accuracy of sentinel lymph node biopsy in squamous cell carcinoma of the oropharynx,larynx, and hypopharynx: A systematic review and meta-analysis[J]. Head & Neck, 2022, 44(11): 2621-2632.
[9] 冯成敏, 朱鑫, 程瑶, 等. 喉鳞状细胞癌组织中MUC13 的表达及临床意义[J]. 川北医学院学报,2023, 38(2)：160-164. FENG Chengmin, ZHU Xin, CHENG Yao, et al. Expression and clinical significance of MUC13 in laryngeal squamous cell carcinoma[J]. Journal of North Sichuan Medical College, 2023, 38(2): 160-164.
[10] MADDEN E, LOGUE S E, HEALY S J, et al. The role of the unfolded protein response in cancer progression:From oncogenesis to chemoresistance[J].Biology of the Cell, 2019, 111(1): 1-17.
[11] COLEMAN O I, HALLER D. ER stress and the UPR in shaping intestinal tissue homeostasis and immunity[J].Frontiers in Immunology, 2019, 10: 2825.
[12] PENG Fusen, ZHANG Hailin, DU Youhong, et al. Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of TXNDC5[J]. Molecular Medicine Reports, 2018,17(3): 4767-4776.
[13] 李倩, 范妤, 史晓燕, 等. 内质网应激诱导的自噬在肝脏疾病中的研究进展[J]. 生命科学, 2021, 33(7)：876-887. LI Qian, FAN Yu, SHI Xiaoyan, et al. Research progress of endoplasmic reticulum stress-induced autophagy in liver diseases[J]. Chinese Bulletin of Life Sciences, 2021, 33(7): 876-887.
[14] JEON Y J, KIM T, PARK D, et al. MiRNA-mediated TUSC3 deficiency enhances UPR and ERAD to promote metastatic potential of NSCLC[J]. Nature Communications, 2018, 9(1): 5110.
[15] LI Ruohan, ZHOU Huaixiang, LI Mingzhe, et al. Gremlin-1 promotes colorectal cancer cell metastasis by activating ATF6 and inhibiting ATF4 pathways[J].Cells, 2022, 11(14): 2136.
[16] KANG J I, KIM D H, SUNG K W, et al. p62-induced cancer-associated fibroblast activation via the Nrf2-ATF6 pathway promotes lung tumorigenesis[J].Cancers, 2021, 13(4): 864.
[17] 柳青, 田娜, 王慧杰. 食管癌患者血清中血管内皮生长因子和胰岛素样生长因子-1 表达及其与临床病理特征的关系[J]. 实用癌症杂志, 2022, 37(1)：54-56,67. LIU Qing, TIAN Na, WANG Huijie. The expresssion of VEGF and IGF-1 in esophageal cancer and its clinical significance[J]. The Practical Journal of Cancer, 2022,37(1): 54-56, 67.
[18] 姜秋利, 鲁华东, 郑景妹, 等. 结直肠癌组织中RREB1 和ANKRD1 的表达与临床病理特征和预后的相关性研究[J]. 现代检验医学杂志, 2023, 38(1)：16-21. JIANG Qiuli, LU Huadong, ZHENG Jingmei, et al. Correlation between the expression of RREB1 and ANKRD1 and clinicopathological features and prognosis in colorectal cancer[J]. Journal of Modern Laboratory Medicine, 2023, 38(1): 16-21.
[19] SHI Weiye, YAO Xu, FU Yu, et al. Interferon-α and its effects on cancer cell apoptosis[J]. Oncology Letters,2022, 24(1): 235.
[20] 刘美君, 丁治国, 陈晓珩, 等. 参芪注射液协同IFN-α 抑制肝癌细胞体外增殖、迁移能力和侵袭性的研究[J]. 中国现代普通外科进展, 2022, 25(12)：925-927, 932. LIU Meijun, DING Zhiguo, CHEN Xiaohang, et al. Shenqi Fuzheng injection combined with interferon alpha on the proliferation and invasiveness of hepatocellular carcinoma cells in vitro[J]. Chinese Journal of Current Advances in General Surgery, 2022,25(12): 925-927, 932.
[21] TIRONE N R, CAMPOS C G, FERREIRA K J A, et al. Pathways of IFN-alpha activation in patients with Cervical Intraepithelial Neoplasia (CIN)[J]. Revista Brasileira De Ginecologia e Obstetricia, 2021, 43(9):682-689.
[22] 谢淼, 沙文, 崔庆明, 等. 等离子电切术联合丝裂霉素C 及干扰素-α 膀胱灌注化疗治疗浅表性膀胱癌的疗效及预后分析[J]. 癌症进展, 2020, 18(2)：195-197. XIE Miao, SHA Wen, CUI Qingming, et al. Efficacy and prognosis of plasmakinetic resection combined with intravesical instillation of mitomycin C and interferon-a in the treatment of superficial bladder cancer[J]. Oncology Progress, 2020, 18(2): 195-197.

备注/Memo

备注/Memo:
基金项目：河南省医学科技攻关计划项目（LHGJ20220680）：不同前庭康复时机在前庭神经炎急性期患者中的疗效分析。
作者简介：席恺（1973-），女，博士研究生，主任医师，研究方向：喉癌，耳鼻咽喉科学，E-mail：blossom_2021@163.com。
更新日期/Last Update: 2024-03-15