Correlation between serum C peptide and insulin-like growth factor binding protein 3 and the risk of breast cancer patient death

doi:10.3969/j.issn.1673-8640.2022.01.007

Abstract

Abstract:

Objective To investigate the correlation between serum C peptide and insulin-like growth factor binding protein 3（IGFBP-3） and the risk of breast cancer patient death. Methods Totally,339 patients with breast cancer were enrolled and followed up for 2-4 years. The general clinical data（age,sex,physical activity,smoking history,drinking history,height,body mass and waist circumference） of all the patients were collected,the body mass index（BMI） was calculated,and the levels of C peptide,fasting insulin（FINS）,fasting blood glucose（FBG）,serum creatinine（SCr） and IGFBP-3 were determined. Cox regression analysis was used to assess the relationship between the indicators and the risk of breast cancer patient death. Results BMI,waist circumference,C peptide and IGFBP-3 levels in death group were higher than those in survival group（P<0.05）. There was no statistical significance in the other indicators between the 2 groups（P>0.05）. According to the four percentiles of C peptide,the patients were classified into 4 groups. Compared with those of C peptide≤0.39 nmol/L,serum IGFBP-3 levels of C peptide 0.40-0.62 nmol/L group,C peptide 0.63-1.02 nmol/L group,C peptide≥1.03 nmol/L group were increased（P<0.05） with the trend of P<0.000 1,indicating that it was related to C peptide. According to FINS's four percentiles,4 subgroups of breast cancer patients were grouped. There was no statistical significance in serum IGFBP-3 level among the 4 groups（P>0.05） with the trend of P>0.05,indicating that serum IGFBP-3 had no relation with FINS level. Cox regression analysis showed that C peptide and IGFBP-3 were related to the risk of breast cancer patient death after fully correcting the confounding factors. The hazard ratios（HR） were 1.58 and 1.02,respectively,the 95% confidence intervals（CI） ranged from 1.09 to 2.66 and from 1.01 to 1.91,and the P values were 0.02 and 0.01. Conclusions C peptide and serum IGFBP-3 are related to the risk of breast cancer patient death.

Key words: C peptide, Insulin-like growth factor binding protein-3, Breast cancer

CLC Number:

R446.1

ZHANG Xinyue, CHEN Liang, ZHENG Yu. Correlation between serum C peptide and insulin-like growth factor binding protein 3 and the risk of breast cancer patient death[J]. Laboratory Medicine, 2022, 37(1): 36-40.

Figures/Tables 5

References 30

[1]	TORRE L A, BRAY F, SIEGEL R L, et al. Global cancer statistics,2012[J]. CA Cancer J Clin, 2015, 65(2):87-108. DOI URL
[2]	SHIOVITZ S, KORDE L A. Genetics of breast cancer:a topic in evolution[J]. Ann Oncol, 2015, 26(7):1291-1299. DOI URL
[3]	张前进, 胡金娥, 胡一川, 等. 血清降脂素及维生素D与2型糖尿病患者胰岛β细胞功能及胰岛素敏感性的相关性[J]. 检验医学, 2020, 35(9):908-911.
[4]	何珊, 邓露, 蔡志福, 等. 脂联素对高脂饮食诱导的胰岛素抵抗子宫内膜癌裸鼠移植瘤生长的影响[J]. 中国癌症防治杂志, 2020, 12(2):186-190.
[5]	JOGIE-BRAHIM S, FELDMAN D, OH Y. Unraveling insulin-like growth factor binding protein-3 actions in human disease[J]. Endocr Rev, 2019, 30(5):417-437. DOI URL
[6]	LANDREH M, STUKENBORG J B, WILLANDER H, et al. Proinsulin C-peptide interferes with insulin fibril formation[J]. Biochem Biophys Res Commun, 2012, 418(3):489-493. DOI URL
[7]	NISHIHARA K, SUZUKI Y, ROH S. Ruminal epithelial insulin-like growth factor-binding proteins 2,3,and 6 are associated with epithelial cell proliferation[J]. Anim Sci J, 2020, 91(1):e13422.
[8]	KRIEGE M, SEYNAEVE C, MEIJERS-HEIJBOER H, et al. Sensitivity to first-line chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers[J]. J Clin Oncol, 2009, 27(23):3764-3771. DOI URL
[9]	LI Y, ZHAO D, LI Y, et al. Serum C-peptide as a key contributor to lipid-related residual cardiovascular risk in the elderly[J]. Arch Gerontol Geriatr, 2017, 73:263-268. DOI URL
[10]	LEE K, KRUPER L, DIELI-CONWRIGHT C M, et al. The impact of obesity on breast cancer diagnosis and treatment[J]. Curr Oncol Rep, 2019, 21(5):41. DOI URL
[11]	SPIELMAN L J, LITTLE J P, KLEGERIS A. Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration[J]. J Neuroimmunol, 2014, 273(1-2):8-21. DOI URL
[12]	COHEN D H, LEROITH D. Obesity,type 2 diabetes,and cancer:the insulin and IGF connection[J]. Endocr Relat Cancer, 2012, 19(5):F27-F45. DOI URL
[13]	REDDY R C, HAO Y, LEE S H, et al. Pioglitazone reverses insulin resistance and impaired CCK-stimulated pancreatic secretion in eNOS(-/-) mice:therapy for exocrine pancreatic disorders?[J]. Am J Physiol Gastrointest Liver Physiol, 2007, 293(1):G112-G120. DOI URL
[14]	VISH M G, MANGESHKAR P, PIRAINO G, et al. Proinsulin c-peptide exerts beneficial effects in endotoxic shock in mice[J]. Crit Care Med, 2007, 35(5):1348-1355. DOI URL
[15]	WANG E A, CHEN W Y, WONG C H. Multiple growth factor targeting by engineered insulin-like growth factor binding protein-3 augments EGF receptor tyrosine kinase inhibitor efficacy[J]. Sci Rep, 2020, 10(1):2735. DOI URL
[16]	ZHANG M Q, GAO J L, LIAO X D, et al. MiR-454 regulates triglyceride synjournal in bovine mammary epithelial cells by targeting PPAR-γ[J]. Gene, 2019, 691:1-7. DOI URL
[17]	LIANGGENG X, BAIWU L, MAOSHU B, et al. Impact of interaction between PPAR alpha and PPAR gamma on breast cancer risk in the Chinese Han population[J]. Clin Breast Cancer, 2017, 17(5):336-340. DOI URL
[18]	AL-RASHEED N M, CHANA R S, BAINES R J, et al. Ligand-independent activation of peroxisome proliferator-activated receptor-gamma by insulin and C-peptide in kidney proximal tubular cells:dependent on phosphatidylinositol 3-kinase activity[J]. J Biol Chem, 2004, 279(48):49747-49754. DOI URL
[19]	ZHAO J, ZHI Z, WANG C, et al. Exogenous lipids promote the growth of breast cancer cells via CD36[J]. Oncol Rep, 2017, 38(4):2105-2115. DOI URL
[20]	CUI P, CHEN Y, WAILI N, et al. Associations of serum C-peptide and insulin-like growth factor binding proteins-3 with breast cancer deaths[J]. PLoS One, 2020, 15(11):e0242310. DOI URL
[21]	SISTI G, DI TOMMASO M, PACCOSI S, et al. Unique associations between insulin-like growth factor binding protein-1,insulin-like growth factor-1 and T cell immunoglobulin Mucin 3 in successful twin pregnancies conceived with donor oocytes[J]. Medicina (Kaunas), 2019, 55(5):144.
[22]	YANG J, HU Y, WU J, et al. Effects of IGFBP-3 and GalNAc-T14 on proliferation and cell cycle of glioblastoma cells and its mechanism[J]. J Pharm Pharmacol, 2020, 72(2):218-226. DOI URL
[23]	CAI Q, DOZMOROV M, OH Y. IGFBP-3/IGFBP-3 receptor system as an anti-tumor and anti-metastatic signaling in cancer[J]. Cells, 2020, 9(5):1261. DOI URL
[24]	BURGER A M, LEYLAND-JONES B, BANERJEE K, et al. Essential roles of IGFBP-3 and IGFBP-rP1 in breast cancer[J]. Eur J Cancer, 2005, 41(11):1515-1527. DOI URL
[25]	RAVAL A, TRIVEDI S. Breast cancer:role of IGF-1 and IGFBP-3 expression in prognostication[J]. Indian J Exp Biol, 2016, 54(10):619-629.
[26]	PROBST-HENSCH N M, STEINER J H, SCHRAML P, et al. IGFBP2 and IGFBP3 protein expressions in human breast cancer:association with hormonal factors and obesity[J]. Clin Cancer Res, 2010, 16(3):1025-1032. DOI URL
[27]	RENEHAN A G, ZWAHLEN M, MINDER C, et al. Insulin-like growth factor(IGF)-I,IGF binding protein-3,and cancer risk:systematic review and meta-regression analysis[J]. Lancet, 2004, 363(9418):1346-1353. DOI URL
[28]	GHORBANI A, SHAFIEE-NICK R, ZOJAJI S A, et al. Physiological effects of proinsulin-connecting peptide in human subcutaneous adipose tissue[J]. Physiol Int, 2017, 104(2):193-205. DOI URL
[29]	YOSTEN G L, KOLAR G R, REDLINGER L J, et al. Evidence for an interaction between proinsulin C-peptide and GPR146[J]. J Endocrinol, 2013, 218(2):B1-B8. DOI URL
[30]	ZHANG A M Y, WELLBERG E A, KOPP J L, et al. Hyperinsulinemia in obesity,inflammation,and cancer[J]. Diabetes Metab J, 2021, 45(3):285-311. DOI URL

组别	例数	年龄/岁	BMI/（kg/m²）		吸烟史/[例（%）]		饮酒史/[例（%）]	腰围/cm
死亡组	23	53.6±5.1	27.3±2.7		3（13）		4（17.4）	100.4±16.6
存活组	316	55.4±4.3	24.9±4.2		47（15）		59（18.6）	91.5±15.1
t值		-1.913	2.698		1.523		2.313	3.145
P值		0.06	0.007		0.077		0.369	0.0001
组别	C肽/（nmol/L）			FINS/（pmol/L）		FBG/（mmol/L）	SCr/（μmol/L）	IGFBP-3/（ng/mL）
死亡组	6.4±3.4			93.3±16.1		5.7±1.8	88.6±18.6	4 692.7±51.9
存活组	5.6±2.2			78.8±13.9		5.3±2.1	86.7±20.8	3 987.2±52.8
t值	2.198			1.572		3.154	3.421	2.921
P值	0.002			0.376		0.060	0.655	0.001

组别	例数	年龄/岁	BMI/（kg/m²）		吸烟史/[例（%）]		饮酒史/[例（%）]	腰围/cm
死亡组	23	53.6±5.1	27.3±2.7		3（13）		4（17.4）	100.4±16.6
存活组	316	55.4±4.3	24.9±4.2		47（15）		59（18.6）	91.5±15.1
t值		-1.913	2.698		1.523		2.313	3.145
P值		0.06	0.007		0.077		0.369	0.0001
组别	C肽/（nmol/L）			FINS/（pmol/L）		FBG/（mmol/L）	SCr/（μmol/L）	IGFBP-3/（ng/mL）
死亡组	6.4±3.4			93.3±16.1		5.7±1.8	88.6±18.6	4 692.7±51.9
存活组	5.6±2.2			78.8±13.9		5.3±2.1	86.7±20.8	3 987.2±52.8
t值	2.198			1.572		3.154	3.421	2.921
P值	0.002			0.376		0.060	0.655	0.001

项目	HR（95%CI）	P值
年龄	1.02（1.01~1.21）	0.003
BMI	1.03（1.01~1.13）	0.002
吸烟史	1.21（1.11~1.32）	0.001
饮酒史	1.08（1.03~1.17）	0.004
C肽	1.67（1.32~1.89）	0.007
FINS	1.05（1.02~1.22）	0.002
FBG	1.03（1.01~1.31）	0.004
腰围	1.01（0.98~1.29）	0.320
SCr	1.08（1.02~1.19）	0.030
IGFBP-3	1.91（1.23~3.17）	0.000 1

项目	HR（95%CI）	P值
年龄	1.02（1.01~1.21）	0.003
BMI	1.03（1.01~1.13）	0.002
吸烟史	1.21（1.11~1.32）	0.001
饮酒史	1.08（1.03~1.17）	0.004
C肽	1.67（1.32~1.89）	0.007
FINS	1.05（1.02~1.22）	0.002
FBG	1.03（1.01~1.31）	0.004
腰围	1.01（0.98~1.29）	0.320
SCr	1.08（1.02~1.19）	0.030
IGFBP-3	1.91（1.23~3.17）	0.000 1

组别	例数	IGFBP-3/（ng/mL）
C肽≤0.39 nmol/L组	84	4 190.72±39.21
C肽0.40~0.62 nmol/L组	85	4 235.46±33.46^*
C肽0.63~1.02 nmol/L组	85	4 418.23±30.54^**
C肽≥1.03 nmol/L组	85	4 529.16±43.12^**