Relationship Between the Expression of Human Matricellular Protein 3 and the Pathological Features, Drug Resistance, and Prognosis of Gastric Cancer Based on Immunohistochemical Method

To observe the relationship between the expression of human matricellular protein 3 (MATN3) and the pathological features, drug resistance, and prognosis of gastric cancer based on immunohistochemical method.
Methods A total of 100 gastric cancer patients treated at the First Affiliated Hospital of Bengbu Medical College from January 2022 to December 2022 were included. MATN3 expression in gastric cancer tissues and paracancerous tissues was assessed by immunohistochemistry. The expression of MATN3 was compared across pathological features. Patients were divided into sensitive and resistant groups based on chemotherapy resistance, and MATN3 expression was compared between these groups. The relationship between MATN3 and recurrence-free survival (RFS) and overall survival (OS) of gastric cancer patients was analyzed using Kaplan-Meier survival curves. Univariate and multifactorial Cox regression analyses were used to analyze the factors affecting the prognosis of gastric cancer patients. Human gastric cancer cells MGC803 were transfected with MATN3. The cells were divided into a high expression group (LV-MATN3 group) and its control group (LV-NC group) and a low expression group (sh-MATN3 group) and its control group (sh-NC group). Cell proliferation was assessed using the CCK8 assay, cell migration and invasion were assessed using the Transwell assay, and MATN3 mRNA expression levels were measured using RT-qPCR. A nude mouse xenograft model was constructed by hypodermic injection of MGC-803 cells transfected with MATN3, and MATN3 mRNA expression levels in tumor tissues were measured using RT-qPCR.
Results Immunohistochemical results showed a significantly higher rate of high MATN3 expression in gastric cancer tissues (64.00%, 64/100) compared to adjacent non-cancerous tissues (31.00%, 31/100) (P<0.05). High MATN3 expression was associated with age ≥60 years old, tumor location in the gastric body, tumor size ≥5 cm, lymph node metastasis (N1-N3), histological differentiation (moderate to high), tumor invasion depth (T3-T4), TNM stage (Ⅲ-Ⅳ), distant organ metastasis, recurrence, and mortality (P<0.05). Among patients with chemotherapy resistance, the high MATN3 expression rate was 79.49% (31/39) in the resistant group compared to 54.10% (33/61) in the sensitive group (P<0.05). Follow-up duration ranged from 11 to 22 months, with a 97.00% follow-up rate and 3 cases lost to follow-up. Kaplan-Meier survival curve analysis showed that patients with high MATN3 expression had significantly lower RFS and OS compared to those with low MATN3 expression (RFS: log-rank=17.291, P<0.001; OS: log-rank=21.719, P<0.001). Multivariate Cox analysis identified high MATN3 expression (hazard ratio [HR]=2.291, 95% confidence interval [CI]: 1.268-5.392), tumor location in the gastric body (HR=2.057, 95% CI: 1.441-5.666), lymph node metastasis (N1-N3) (HR=2.011, 95% CI: 1.010-2.274), tumor invasion depth (T3-T4) (H=2.977, 95% CI: 1.032-7.853), TNM stage Ⅲ-Ⅳ (HR=2.008, 95% CI: 1.049-3.902), and distant organ metastasis (HR=2.505, 95% CI: 1.529-5.000) as independent risk factors affecting RFS and OS (P<0.05). Cell and animal experiments demonstrated that compared to the LV-NC group, the LV-MATN3 group exhibited significantly higher cell proliferation, migration, and invasion (P<0.05), as well as increased tumor volume and MATN3 mRNA expression in tumor tissues (P<0.05). Conversely, the sh-MATN3 group showed significantly reduced cell proliferation, migration, and invasion, along with decreased tumor volume and MATN3 mRNA levels compared to the sh-NC group (P<0.05).
Conclusion MATN3 is highly expressed in gastric cancer tissues and is associated with various pathological features, drug resistance and poor prognosis. MATN3 holds potential as a diagnostic marker for poor prognosis and may play a role in the malignant behaviors of gastric cancer cells, including proliferation, migration, and invasion.

 

Keywords: Immunohistochemistry, MATN3, Gastric cancer, Pathological features, Drug resistance, Prognosis, Relationship

 

ZHANG L, ZHANG W, SHANG G F. Application of serum TK1, CEA and CA19-9 detection in the diagnosis of gastric cancer and their correlation with pathological features of gastric cancer. Lab Med Clin, 2022, 19(9): 1237–1240. doi: 10.3969/j.issn.1672-9455.2022.09.022.

SONG Y Y, LI X L. Correlation of the expression of p-STAT3 protein with prognosis and clinicopatho-logical characteristics in gastric cancer patients: a meta-analysis. Chin J Gastroenterol Hepatol, 2020, 29(2): 148–154. doi: 10.3969/j.issn.1006-5709.2020.02.006.

LIU Q W, LI Y, TAN B B, et al. Clinicopathological characteristics and lymph node metastasis in patients with early gastric cancer. Chin J Gen Surg, 2022, 37(4): 255–259. doi: 10.3760/cma.j.cn113855-20210831-00525.

HE W, LIANG B, WANG C, et al. MSC-regulated lncRNA MACC1-AS1 promotes stemness and chemoresistance through fatty acid oxidation in gastric cancer. Oncogene, 2019, 38(23): 4637–4654. doi: 10.1038/s41388-019-0747-0.

WEI C, LI M, LIN S, et al. Characterization of tumor mutation burden-based gene signature and molecular subtypes to assist precision treatment in gastric cancer. Biomed Res Int, 2022, 2022: 4006507. doi: 10.1155/2022/ 4006507.

DASA V, EASTWOOD J R B, PODGORSKI M, et al. Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia. Am J Med Genet A, 2019, 179(4): 534–541. doi: 10.1002/ajmg.a. 61049.

THRIFT A P, El-SERAG H B. Burden of gastric cancer. Clin Gastroenterol Hepatol, 2020, 18(3): 534–542. doi: 10.1016/j.cgh.2019.07. 045.

LUO A, ZHU X Y, HU Y D, et al. Analysis of prognosis-related genes of gastric cancer based on tumor stromal score. J Tongji Univ (Med Sci), 2020, 41(4): 418–425. doi: 10.16118/j.1008-0392.2020.04.003.

WU P L. Expression level of MATN3 in gastric cancer and its clinical prognostic significance. Hefei: Anhui Medical University, 2018. doi: 10. 7666/d.D01503271.

沿杂志(电子版), 2012, 4(5): 62–71. doi: 10.3969/j.issn.1674-7372.2012.05. 015.

Department of Medical Administration, Ministry of Health, People's Republic of China. Gastric cancer diagnosis and treatment guidelines (2011 edition). Chin J Front Med Sci (E Vers), 2012, 4(5): 62–71. doi: 10. 3969/j.issn.1674-7372.2012.05.015.

LAI M Y, KANG S Y, SUN Y T, et al. Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systemic therapy of gastric cancer. BMC Cancer, 2022, 22(1): 1031. doi: 10.1186/s12885-022-10125-1.

ZHONG L, HUANG T, XIE X H, et al. Correlation between XRCC1 gene Arg194Trp polymorphism and platinum-based chemotherapy in patients with gastric cancer. Shandong Med J, 2017, 57(8): 5–8. doi: 10.3969/j.issn. 1002-266X.2017.08.002.

WANG P, XIAO W S, LI Y H, et al. Identification of MATN3 as a novel prognostic biomarker for gastric cancer through comprehensive TCGA and GEO data mining. Dis Markers, 2021, 2021: 1769635. doi: 10.1155/ 2021/1769635.

JIA X, CHEN B, LI Z, et al. Identification of a four-gene-based SERM signature for prognostic and drug sensitivity prediction in gastric cancer. Front Oncol, 2022, 11: 799223. doi: 10.3389/fonc.2021.799223.

YUAN L, XU Z Y, RUAN S M, et al. Long non-coding RNAs towards precision medicine in gastric cancer: early diagnosis, treatment, and drug resistance. Mol Cancer, 2020, 19(1): 96. doi: 10.1186/s12943-020-01219-0.

LI D, XU J, DONG X, et al. Diagnostic and prognostic value of MATN3 expression in gastric carcinoma: TCGA database mining. J Gastrointest Oncol, 2021, 12(4): 1374–1383. doi: 10.21037/jgo-21-267.