Expression and clinical significance of STIP1 in triple negative breast cancer

doi:10.3877/cma.j.issn.1674-3946.2024.01.015

Abstract

Abstract:

Objective

To analyze the relationship between the expression of phosphorylated stress-induced protein-1 (STIP1) and clinicopathological features and prognosis in triple negative breast cancer (TNBC).

Methods

Cancer tissues of 105 TNBC patients who underwent surgical treatment from January 2020 to October 2022 were collected for study, and focal tissues of 105 breast fibroadenoma patients who underwent surgical treatment during the same period were selected as controls. Immunohistochemical staining and real-time fluorescence quantitative PCR were used to detect STIP1 protein and mRNA expression in TNBC tissues and fibronenoma tissues. SPSS 24.0 was used to complete the data analysis, and the counting data was compared by χ² test. Measurement data were expressed as（）, and t test was used for comparison between groups. Kaplan-Meier survival curve was used to analyze the relationship between STIP1 expression and prognosis of TNBC patients. P<0.05 was considered statistically significant.

Results

The positive rate and mRNA expression levels of STIP1 protein in TNBC tissues were significantly higher than those in breast fibroadenoma tissues (P<0.05). The expression of STIP1 protein in TNBC tissues was significantly correlated with TNM stage, histological grade, Nottingham prognosis index and Ki-67 level (P<0.05). The cumulative overall survival (OS) and cumulative disease-free survival (DFS) of STIP1 positive expression group were significantly lower than those of negative expression group, with statistical significance (Log-Rankχ²=4.716, 4.457, P=0.035, 0.041).

Conclusion

Significant positive/high expression of STIP1 in TNBC tissues is closely related to pathological characteristics such as TNM stage, histological grade, Nottingham prognosis index and Ki-67 level and patient prognosis, which may be involved in disease progression and can be used as an important biomarker for early diagnosis and prognosis of potential TNBC patients.

Key words: Triple Negative Breast Cancer, Stress Induced Phosphoprotein-1, Clinicopathology, Prognosis

Yansong Li, Huimin Feng, Mingchao Liu, Zepeng Liu, Qiuxia Jiang. Expression and clinical significance of STIP1 in triple negative breast cancer[J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(01): 52-56.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhpwkssxzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-3946.2024.01.015

https://zhpwkssxzz.cma-cmc.com.cn/EN/Y2024/V18/I01/52

Figures/Tables 4

References 20

[1]	李传书,葛述科,高伟,等.大连市不同型别乳腺癌患者的临床病理特征与生存状况研究[J/CD].中华普外科手术学杂志（电子版）, 2020, 14(03): 268–272.
[2]	岳雁鸿,王瑶,曾燕.保乳术、改良根治术和改良根治术联合放疗治疗三阴性乳腺癌术后局部复发情况比较[J/CD].中华普外科手术学杂志（电子版）, 2019, 13(02): 177–179.
[3]	Chao A，Liao MJ，Chen SH，et al. JAK2-Mediated Phosphorylation of Stress-Induced Phosphoprotein-1（STIP1）in Human Cells[J]. Int J Mol Sci, 2022, 23(5): 2420.
[4]	Lin CY，Chen SH，Tsai CL，et al. Intracellular targeting of STIP1 inhibits human cancer cell line growth[J]. Transl Cancer Res, 2021, 10(3): 1313–1323.
[5]	Bhattacharya K，Picard D. The Hsp70-Hsp90 go-between Hop/Stip1/Sti1 is a proteostatic switch and may be a drug target in cancer and neurodegeneration[J]. Cell Mol Life Sci, 2021, 78(23): 7257–7273.
[6]	Lin L，Wen J，Lin B，et al. Stress-induced phosphoprotein 1 facilitates breast cancer cell progression and indicates poor prognosis for breast cancer patients[J]. Hum Cell, 2021, 34(3): 901–917.
[7]	仇艳,王惠,凌梦妍.生殖因素与三阴性乳腺癌发生和预后的关系[J].中国妇幼保健, 2022, 37(02): 226–229.
[8]	Lackie RE，de Miranda AS，Lim MP，et al. Stress-inducible phosphoprotein 1（HOP/STI1/STIP1）regulates the accumulation and toxicity of α-synuclein in vivo[J]. Acta Neuropathol, 2022, 144(5): 881–910.
[9]	Beckley SJ，Hunter MC，Kituyi SN，et al. STIP1/HOP Regulates the Actin Cytoskeleton through Interactions with Actin and Changes in Actin-Binding Proteins Cofilin and Profilin[J]. Int J Mol Sci, 2020, 21(9): 3152.
[10]	M Fouad E，A Harb O，Reham Amin S，et al. The Expression of FOXE-1 and STIP-1 in Papillary Thyroid Carcinoma and Their Relationship with Patient Prognosis[J]. Iran J Pathol, 2018, 13(2): 256–271.
[11]	Wang JH，Gong C，Guo FJ，et al. Knockdown of STIP1 inhibits the invasion of CD133positive cancer stemlike cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways[J]. Int J Mol Med, 2020, 46(6): 2251–2259.
[12]	娄志刚,袁波,谭占国. STIP1对胶质瘤U251细胞增殖、侵袭和凋亡的影响[J].中国临床神经外科杂志, 2020, 25(12): 847–850.
[13]	Jing Y，Liang W，Liu J，et al. Stress-induced phosphoprotein 1 promotes pancreatic cancer progression through activation of the FAK/AKT/MMP signaling axis[J]. Pathol Res Pract, 2019, 215(11): 152564.
[14]	Sun X，Cao N，Mu L，et al. Stress induced phosphoprotein 1 promotes tumor growth and metastasis of melanoma via modulating JAK2/STAT3 pathway[J]. Biomed Pharmacother, 2019, 116: 108962.
[15]	梅放,柳剑英,薛卫成. 浸润性乳腺癌的组织学分级：Nottingham组织学分级系统[J].中华病理学杂志, 2019, 48(08): 659–664.
[16]	Sejben A，Nyári T，Zombori T，et al. Comparison of Nottingham Prognostic Index，PREDICT and PrognosTILs in Triple Negative Breast Cancer -a Retrospective Cohort Study[J]. Pathol Oncol Res, 2020, 26(4): 2443–2450.
[17]	张科,刘志良,陈雪琴,等. BRCA1、AR及Ki-67在三阴性乳腺癌中的表达及临床病理意义[J].实用癌症杂志, 2021, 36(09): 1398–1401.
[18]	袁甲翔,王群,司亚卿,等. 应激诱导磷酸化蛋白1调控分化抑制因子3表达在胃癌细胞上皮-间充质转化及侵袭迁移过程中的作用及其机制[J].中华实验外科杂志, 2018, 35(12): 2265–2268.
[19]	Krafft U，Tschirdewahn S，Hess J，et al. STIP1 Tissue Expression Is Associated with Survival in Chemotherapy-Treated Bladder Cancer Patients[J]. Pathol Oncol Res, 2020, 26(2): 1243–1249.
[20]	詹树恺,刘财广,李娜,等. 磷酸化应激诱导蛋白1在消化系统肿瘤中的研究进展[J]. 广东医学, 2022, 43(05): 652–656.

组织	例	STIP1蛋白（%）		STIP1 mRNA表达
组织	例	阳性	阴性	STIP1 mRNA表达
TNBC	105	86（81.9）	19（18.1）	1.6±0.1
乳腺纤维腺瘤	105	28（26.7）	77（73.3）	0.4±0.1
χ²/t值		64.550		124.910
P值		0.000		0.000

组织	例	STIP1蛋白（%）		STIP1 mRNA表达
组织	例	阳性	阴性	STIP1 mRNA表达
TNBC	105	86（81.9）	19（18.1）	1.6±0.1
乳腺纤维腺瘤	105	28（26.7）	77（73.3）	0.4±0.1
χ²/t值		64.550		124.910
P值		0.000		0.000

临床特征		STIP1蛋白		χ²值	P值
临床特征		阳性（n=86）	阴性（n=19）	χ²值	P值
年龄	≤50岁	49	11	0.005	0.942
年龄	>50岁	37	8	0.005	0.942
肿瘤直径	≤2 cm	40	12	1.725	0.189
肿瘤直径	>2 cm	46	7	1.725	0.189
病理类型	浸润性导管癌	57	12	0.128	0.938
	侵袭性小叶癌	18	4
	其他	11	3
TNM分期	Ⅰ-Ⅱ期	27	13	9.046	0.003
TNM分期	Ⅲ-Ⅳ期	59	6	9.046	0.003
腋窝淋巴结状态	阳性	56	8	3.462	0.063
腋窝淋巴结状态	阴性	30	11	3.462	0.063
组织学分级	Ⅰ级	4	5	2.556	0.011
	Ⅱ级	33	8
	Ⅲ级	49	6
脉管浸润	有	49	8	1.387	0.239
脉管浸润	无	37	11	1.387	0.239
神经侵犯	有	50	7	2.844	0.092
神经侵犯	无	36	12	2.844	0.092
月经状态	绝经	45	11	0.194	0.660
月经状态	未绝经	41	8	0.194	0.660
Nottingham预后指数	<3.4分	5	5	12.126	0.002
	3.4~5.4分	31	10
	>5.4分	50	4
Ki-67水平	≤30%	29	12	5.666	0.017
Ki-67水平	>30%	57	7	5.666	0.017

临床特征		STIP1蛋白		χ²值	P值
临床特征		阳性（n=86）	阴性（n=19）	χ²值	P值
年龄	≤50岁	49	11	0.005	0.942
年龄	>50岁	37	8	0.005	0.942
肿瘤直径	≤2 cm	40	12	1.725	0.189
肿瘤直径	>2 cm	46	7	1.725	0.189
病理类型	浸润性导管癌	57	12	0.128	0.938
	侵袭性小叶癌	18	4
	其他	11	3
TNM分期	Ⅰ-Ⅱ期	27	13	9.046	0.003
TNM分期	Ⅲ-Ⅳ期	59	6	9.046	0.003
腋窝淋巴结状态	阳性	56	8	3.462	0.063
腋窝淋巴结状态	阴性	30	11	3.462	0.063
组织学分级	Ⅰ级	4	5	2.556	0.011
	Ⅱ级	33	8
	Ⅲ级	49	6
脉管浸润	有	49	8	1.387	0.239
脉管浸润	无	37	11	1.387	0.239
神经侵犯	有	50	7	2.844	0.092
神经侵犯	无	36	12	2.844	0.092
月经状态	绝经	45	11	0.194	0.660
月经状态	未绝经	41	8	0.194	0.660
Nottingham预后指数	<3.4分	5	5	12.126	0.002
	3.4~5.4分	31	10
	>5.4分	50	4
Ki-67水平	≤30%	29	12	5.666	0.017
Ki-67水平	>30%	57	7	5.666	0.017

Please choose a citation manager

Content to export