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p62/SQSTM1 高表达预示胰腺癌患者生存时间更短。

High expression of p62/SQSTM1 predicts shorter survival for patients with pancreatic cancer.

机构信息

Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Department of Surgery, Sahlgrenska University Hospital, Sahlgrenska, Vita Stråket 12, paviljong plan 2, SE-413 45, Gothenburg, Sweden.

出版信息

BMC Cancer. 2022 Mar 30;22(1):347. doi: 10.1186/s12885-022-09468-6.

DOI:10.1186/s12885-022-09468-6
PMID:35354432
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8969328/
Abstract

BACKGROUND

Accumulation of the signal adaptor protein p62 has been demonstrated in many forms of cancer, including pancreatic ductal adenocarcinoma (PDAC). Although data from experimental studies suggest that p62 accumulation accelerates the development of PDAC, the association between p62 protein expression and survival in PDAC patients is unclear.

METHODS

Thirty-three tumor specimens from PDAC patients treated by primary surgery were obtained. Immunohistochemical expression of p62, microtubule-associated protein 1A/1B-light chain 3 (LC3), and nuclear factor-erythroid factor 2-related factor 2 (NRF2) in tumor tissue was examined for associations with clinicopathological characteristics and disease-specific survival (DSS).

RESULTS

There was no association between p62 expression and any of the clinicopathological variables. However, high p62 protein expression in tumor cells was significantly associated with shorter DSS (7 months vs. 29 months, p = 0.017). The hazard ratio for death in patients with high p62 protein expression in tumor cells was 2.88 (95% confidence interval: 1.17-7.11, p = 0.022). In multivariable analysis, high p62 expression was an independent prognostic factor for shorter DSS (p = 0.020) when follow up time was more than 5 years. LC3 and NRF2 staining was not associated with survival or other clinicopathological parameters.

CONCLUSION

Our results show that high p62 protein expression in tumor cells is associated with shorter survival following pancreatic tumor resection. This association supports a role for p62 as a prognostic marker in patients with PDAC treated by primary surgery.

摘要

背景

信号衔接蛋白 p62 的积累已在多种癌症中得到证实,包括胰腺导管腺癌(PDAC)。尽管来自实验研究的数据表明,p62 的积累会加速 PDAC 的发展,但 p62 蛋白表达与 PDAC 患者生存之间的关联尚不清楚。

方法

收集了 33 例接受根治性手术治疗的 PDAC 患者的肿瘤标本。检测肿瘤组织中 p62、微管相关蛋白 1A/1B-轻链 3(LC3)和核因子-红细胞 2 相关因子 2(NRF2)的免疫组织化学表达,以探讨与临床病理特征和疾病特异性生存(DSS)的关系。

结果

p62 表达与任何临床病理变量均无相关性。然而,肿瘤细胞中 p62 蛋白表达较高与 DSS 较短显著相关(7 个月与 29 个月,p=0.017)。肿瘤细胞中 p62 蛋白表达较高的患者死亡风险比为 2.88(95%置信区间:1.17-7.11,p=0.022)。在多变量分析中,当随访时间超过 5 年时,肿瘤细胞中高 p62 表达是 DSS 较短的独立预后因素(p=0.020)。LC3 和 NRF2 染色与生存或其他临床病理参数均无相关性。

结论

我们的研究结果表明,肿瘤细胞中 p62 蛋白表达较高与胰腺肿瘤切除后生存时间较短相关。这种关联支持 p62 作为接受根治性手术治疗的 PDAC 患者的预后标志物的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616d/8969328/fa1bcb668c1b/12885_2022_9468_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616d/8969328/2ae5baf32a00/12885_2022_9468_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616d/8969328/ee83c5674f88/12885_2022_9468_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616d/8969328/a0b1a04b8d31/12885_2022_9468_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616d/8969328/861a84409753/12885_2022_9468_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616d/8969328/fa1bcb668c1b/12885_2022_9468_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616d/8969328/2ae5baf32a00/12885_2022_9468_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616d/8969328/ee83c5674f88/12885_2022_9468_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616d/8969328/a0b1a04b8d31/12885_2022_9468_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616d/8969328/861a84409753/12885_2022_9468_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/616d/8969328/fa1bcb668c1b/12885_2022_9468_Fig5_HTML.jpg

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