MEIS1表达对胃癌根治术后患者生存期的影响及其在预后评估中的价值

doi:10.13481/j.1671-587X.20240520

Abstract

Abstract:

Objective To discuss the postoperative survival of the gastric cancer patients with different expression levels of myeloid ecotropic viral integration site 1 （MEIS1）， and to analyze the predictive value of MEIS1 expression in the prognosis evaluation of gastric cancer. Methods In a gastric cancer survival cohort， 215 patients who underwent radical gastrectomy were selected. Immunohistochemical staining was used to detect the expression levels of MEIS1 in both gastric cancer and adjacent normal tissues. The relationship between expression level of MEIS1 and the clinicopathological characteristics of the patients were analyzed by χ² test or Fisher’s exact probability method；survival curves were plotted by Kaplan-Meier method； the differences in survival of the patients between MEIS1 high expression group and MEIS1 low expression group were compared by Log-rank test； multivariate Cox proportional hazards regression model was used to calculate the hazard ratios （HR） and 95% confidence intervals （CI） to assess the relationship between MEIS1 expression level and the survival of the gastric cancer patients. Results The immunohistochemical staining result showed that the expression level of MEIS1 in gastric cancer tissue was decreased. The univariate analysis results showed that the patients with high MEIS1 expression had a longer overall survival than those with low expression （P=0.049）， and had a better prognosis. The multivariate Cox proprotional hazards regression analysis results showed that the low MEIS1 expression and high TNM stage were the independent risk factors for poor prognosis of the patients with gastric cancer （HR=1.577， 95%CI： 1.011-2.460， P=0.045； HR=2.709， 95%CI： 1.708-4.297， P<0.001）. Conclusion The gastric cancer patients with low expression of MEIS1 have a shorter postoperative overall survival； MEIS1 is a promising biomarker for prognosis assessment of the patients after radical gastrectomy.

Key words: Myeloid ecotropic viral integration site 1, Gastric cancer, Prognosis, Biomarker, Radical gastrectomy

CLC Number:

R735.2

Jiaxin YI,Yangyu ZHANG,Yingli FU,Yuchen PAN,Yongjie HAN,Jing JIANG,Yanhua WU. Effect of MEIS1 expression on survival in patients after radical gastrectomy and its value in prognostic evaluation[J].Journal of Jilin University(Medicine Edition), 2024, 50(5): 1358-1364.

Figures/Tables 6

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References 23

1	SIEGEL R L， MILLER K D， FUCHS H E， et al. Cancer Statistics， 2021 ［J］. CA Cancer J Clin， 2021， 71（1）： 7-33.
2	VAN CUTSEM E， SAGAERT X， TOPAL B， et al. Gastric cancer［J］. Lancet， 2016， 388（10060）： 2654-2664.
3	FERREIRA H J， HEYN H， VIZOSO M， et al. DNMT3A mutations mediate the epigenetic reactivation of the leukemogenic factor MEIS1 in acute myeloid leukemia［J］. Oncogene， 2017， 36（29）： 4233.
4	ZARGARI S， NEGAHBAN KHAMENEH S， RAD A， et al. MEIS1 promotes expression of stem cell markers in esophageal squamous cell carcinoma［J］. BMC Cancer， 2020， 20（1）： 789.
5	CHEN L， GAO W J， LIN L， et al. A methylation-and immune-related lncRNA signature to predict ovarian cancer outcome and uncover mechanisms of chemoresistance［J］. J Ovarian Res， 2023， 16（1）： 186.
6	GARCIA-CUELLAR M P， PRINZ A， SLANY R K. Meis1 supports leukemogenesis through stimulation of ribosomal biogenesis and Myc［J］. Haematologica， 2022， 107（11）： 2601-2616.
7	GUO Y， GUO H， TONG H Y， et al. The effect Of vascular related CeRNA genes and corresponding imaging biomarkers on survival in lower grade glioma［J］. Ir J Med Sci， 2024， 193（2）： 653-663.
8	ZANGENBERG M， GRUBACH L， AGGERHOLM A， et al. The combined expression of HOXA4 and MEIS1 is an independent prognostic factor in patients with AML［J］. Eur J Haematol， 2009， 83（5）： 439-448.
9	CHENG M X， ZENG Y， ZHANG T， et al. Transcription factor ELF1 activates MEIS1 transcription and then regulates the GFI1/FBW7 axis to promote the development of glioma［J］. Mol Ther Nucleic Acids， 2021， 23： 418-430.
10	CAI G Y， SUN M F， LI X R， et al. Construction and characterization of rectal cancer-related lncRNA-mRNA ceRNA network reveals prognostic biomarkers in rectal cancer［J］. IET Syst Biol， 2021， 15（6）： 192-204.
11	DOOLAN P， CLYNES M， KENNEDY S， et al. TMEM25， REPS2 and Meis 1： favourable prognostic and predictive biomarkers for breast cancer［J］. Tumour Biol， 2009， 30（4）： 200-209.
12	WAN B B， LIU B， WANG Z X， et al. Expression of VEGFR-2 and Meis1 in the early stage of kidney cancers and its clinical significance［J］. J Cent South Univ（Med Sci）， 2020， 45（9）： 1061-1067.
13	MITRA S， MUKHERJEE N， DAS S， et al. Anomalous altered expressions of downstream gene-targets in TP53-miRNA pathways in head and neck cancer［J］. Sci Rep， 2014， 4： 6280.
14	MERIÇ N， KOCABAŞ F. The historical relationship between Meis1 and leukemia［J］. Adv Exp Med Biol， 2022， 1387： 127-144.
15	DONG B Q， LIANG J M， LI D， et al. Identification of a prognostic signature associated with the homeobox gene family for bladder cancer［J］. Front Mol Biosci， 2021， 8： 688298.
16	WANG Z Y， LI X N， CHEN H， et al. Decreased HLF expression predicts poor survival in lung adenocarcinoma［J］. Med Sci Monit， 2021， 27： e929333.
17	XIE H， YU H P， TIAN S T， et al. MEIS-1 level in unresectable hepatocellular carcinoma can predict the post-treatment outcomes of radiofrequency ablation［J］. Oncotarget， 2018， 9（20）： 15252-15265.
18	SONG F， WANG H， WANG Y Y. Myeloid ecotropic viral integration site 1 inhibits cell proliferation， invasion or migration in human gastric cancer［J］. Oncotarget， 2017， 8（52）： 90050-90060.
19	ZHU J， CUI L， XU A X， et al. MEIS1 inhibits clear cell renal cell carcinoma cells proliferation and in vitro invasion or migration ［J］. BMC Cancer， 2017， 17（1）： 176.
20	CHARIOT A， GIELEN J， MERVILLE M P， et al. The homeodomain-containing proteins： an update on their interacting partners［J］. Biochem Pharmacol， 1999， 58（12）： 1851-1857.
21	KITAGAWA Y， IKENAKA A， SUGIMURA R， et al. ZEB2 and MEIS1 independently contribute to hematopoiesis via early hematopoietic enhancer activation［J］. iScience， 2023， 26（10）： 107893.
22	SAHOO B K， LIN Y C， TU C F， et al. Signal peptide-CUB-EGF-like repeat-containing protein 1-promoted FLT3 signaling is critical for the initiation and maintenance of MLL-rearranged acute leukemia［J］. Haematologica， 2023， 108（5）： 1284-1299.
23	CHOI J H， JANG T Y， JEON S E， et al. The small-molecule Wnt inhibitor ICG-001 efficiently inhibits colorectal cancer stemness and metastasis by suppressing MEIS1 expression［J］. Int J Mol Sci， 2021， 22（24）： 13413.

Characteristic	Number of patient	Percentage(η/%)
Gender
Male	169	78.6
Female	46	21.4
Age(year)
≤65	135	62.8
>65	80	37.2
Tumor size
<5 cm	92	42.8
≥5 cm	121	56.3
Unclear	2	0.9
Type
Signet ring cell	16	7.4
Others	199	92.6
Histological grade
Low	44	20.5
High	167	77.7
Unclear	4	1.8
Chemotherapy
Yes	101	53.0
No	114	47.0
TNM stage
Ⅰ/Ⅱ	60	27.9
Ⅲ/Ⅳ	155	72.1
Outcome
Alive	75	34.9
Lost	3	1.4
Dead	137	63.7
MEIS1 expression
Low	32	14.9
High	183	85.1

Clinicopathological parameter	Low expression of MEIS1 (n=32)	High expression of MEIS1 (n=183)	χ²	P
Gender			1.012	0.314
Male	23(13.6)	146(86.4)
Female	9(19.6)	37(80.4)
Age(year)			2.633	0.105
≤65	16(11.9)	119(88.1)
>65	16(20.0)	64(80.0)
Tumor size			1.514	0.219
<5 cm	17(18.5)	75(81.5)
≥5 cm	15(12.4)	106(87.6)
Type			13.965	<0.001
Signet ring cell	8(50.0)	8(50.0)
Others	24(12.1)	175(87.9)
Histological grade			0.024	0.877
Low	7(15.9)	37(84.1)
High	25(15.0)	142(85.0)
Chemotherapy			0.000	0.990
Yes	15(14.9)	86(85.1)
No	17(14.9)	97(85.1)
TNM stage			0.680	0.410
Ⅰ/Ⅱ	7(11.7)	53(88.3)
Ⅲ/Ⅳ	25(16.1)	130(83.9)

Clinicopathological parameter	B	SE	Wald	HR(95%CI)	P
Chemotherapy(Yes vs No)	-0.535	0.176	9.243	0.585(0.415-0.827)	0.002
TNM stage(Ⅲ/Ⅳ vs Ⅰ/Ⅱ)	0.997	0.235	17.944	2.709(1.708-4.297)	<0.001
MEIS1(Low vs High)	0.455	0.227	4.027	1.577(1.011-2.460)	0.045

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Effect of MEIS1 expression on survival in patients after radical gastrectomy and its value in prognostic evaluation

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