|Table of Contents|

Expression of high-temperature requirement factor A1 in medullary thyroid carcinoma tissues and its clinical significance

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2025 01
Page:
38-45
Research Field:
Publishing date:

Info

Title:
Expression of high-temperature requirement factor A1 in medullary thyroid carcinoma tissues and its clinical significance
Author(s):
SUI YiqunXIA Wei
Department of Pathology,the Second Affiliated Hospital of Soochow University,Jiangsu Suzhou 215000,China.
Keywords:
HTRA1medullary thyroid carcinomatumor immunityextracellular matrix
PACS:
R736.1
DOI:
10.3969/j.issn.1672-4992.2025.01.007
Abstract:
Objective:To evaluate the expression of high-temperature requirement factor A1(HTRA1) in medullary thyroid carcinoma(MTC) tissues and to explore its relationship with clinicopathological features,prognosis and tumor immunity.Methods:The expression of HTRA1 protein in 26 cases of MTC tissue was detected by immunohistochemistry.The correlations between HTRA1 protein expression and clinicopathological features and prognosis were analyzed.The relationship between HTRA1 expression and tumor immunity was revealed through bioinformatics.Results:HTRA1 proteins were mainly localized in the cytoplasm in MTC tissues,whereas they were mainly localized in the nucleus in normal thyroid tissues.HTRA1 protein expression was up-regulated in MTC tissues compared with normal thyroid tissues.Clinicopathological analysis showed that the expression of HTRA1 protein was associated with extrathyroidal extension,Hashimoto's thyroiditis and recurrence-free survival.The combined detection of HTRA1 protein,preoperative serum calcitonin and carcinoembryonic antigen had a higher value in predicting extrathyroidal extension,tumor size,tumor T stage and recurrence-free survival.Immunoinfiltration analysis showed that HTRA1 expression was mainly related to immunosuppressive cells.The tumor immune dysfunction and exclusion(TIDE) algorithm revealed that HTRA1 expression in MTC was positively correlated with TIDE score,immune dysfunction,immune exclusion and cancer-associated fibroblast,while it was negatively correlated with microsatellite instability.Gene set enrichment analysis showed that in MTC,HTRA1 expression was mainly associated with gene sets of extracellular matrix and its related signaling pathways.Conclusion:HTRA1 may serve as a new therapeutic target for MTC.The association of HTRA1 with tumor immune function may be helpful for immunotherapy of MTC.

References:

[1]PELIZZO MR,MAZZA EI,MIAN C,et al.Medullary thyroid carcinoma[J].Expert Rev Anticancer Ther,2023,23(9):943-957.
[2]OKA C,SALEH R,BESSHO Y,et al.Interplay between HTRA1 and classical signalling pathways in organogenesis and diseases[J].Saudi J Biol Sci,2022,29(4):1919-1927.
[3]ZHAO W,WU Y,WANG S,et al.HTRA1 promotes EMT through the HDAC6/Ac-α-tubulin pathway in human GBM cells[J].CNS Neurosci Ther,2024,30(2):e14605.
[4]ZHAO Z,LI H,WANG C,et al.Serine protease HtrA1 as an inhibitor on proliferation invasion and migration of gastric cancer[J].Med Oncol,2015,32(4):112.
[5]ZHAO D,LI W,WANG Y,et al.HTRA1 expression is associated with immune-cell infiltration and survival in breast cancer[J].Transl Cancer Res,2023,12(12):3503-3521.
[6]XIA J,WANG F,WANG L,et al.Elevated serine protease HtrA1 inhibits cell proliferation,reduces invasion,and induces apoptosis in esophageal squamous cell carcinoma by blocking the nuclear factor-κB signaling pathway[J].Tumour Biol,2013,34(1):317-328.
[7]WU H,MA S,XIANG M,et al.HTRA1 promotes transdifferentiation of normal fibroblasts to cancer-associated fibroblasts through activation of the NF-κB/bFGF signaling pathway in gastric cancer[J].Biochem Biophys Res Commun,2019,514(3):933-939.
[8]KLOSE R,ADAM MG,WEIS EM,et al.Inactivation of the serine protease HTRA1 inhibits tumor growth by deregulating angiogenesis[J].Oncogene,2018,37(31):4260-4272.
[9]WANG W,ZHAO M,CUI L,et al.Characterization of a novel HDAC/RXR/HtrA1 signaling axis as a novel target to overcome cisplatin resistance in human non-small cell lung cancer[J].Mol Cancer,2020,19(1):134.
[10] LI T,FU J,ZENG Z,et al.TIMER2.0 for analysis of tumor-infiltrating immune cells[J].Nucleic Acids Res,2020,48(W1):W509-W514.
[11] MIAO YR,ZHANG Q,LEI Q,et al.ImmuCellAI:A unique method for comprehensive T-cell subsets abundance prediction and its application in cancer immunotherapy[J].Adv Sci(Weinh),2020,7(7):1902880.
[12] CHEN B,KHODADOUST MS,LIU CL,et al.Profiling tumor infiltrating immune cells with CIBERSORT[J].Methods Mol Biol,2018,1711:243-259.
[13] JIANG P,GU S,PAN D,et al.Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response[J].Nat Med,2018,24(10):1550-1558.
[14] ZURAWA-JANICKA D,KOBIELA J,GALCZYNSKA N,et al.Changes in expression of human serine protease HtrA1,HtrA2 and HtrA3 genes in benign and malignant thyroid tumors[J].Oncol Rep,2012,28(5):1838-1844.
[15] LORENZI T,LORENZI M,ALTOBELLI E,et al.HtrA1 in human urothelial bladder cancer:A secreted protein and a potential novel biomarker[J].Int J Cancer,2013,133(11):2650-2661.
[16] GAGNE A,TETU B,ORAIN M,et al.HtrA1 expression and the prognosis of high-grade serous ovarian carcinoma:A cohort study using digital analysis[J].Diagn Pathol,2018,13(1):57.
[17] KANG I,KIM Y,LEE HK.γδ T cells as a potential therapeutic agent for glioblastoma[J].Front Immunol,2023,14:1273986.
[18] SARKAR I,PATI S,DUTTA A,et al.T-memory cells against cancer:Remembering the enemy[J].Cell Immunol,2019,338:27-31.
[19] ZHANG X,JIANG D,LI S,et al.A signature-based classification of lung adenocarcinoma that stratifies tumor immunity[J].Front Oncol,2023,12:1023833.
[20] POZDEYEV N,ERICKSON TA,ZHANG L,et al.Comprehensive immune profiling of medullary thyroid cancer[J].Thyroid,2020,30(9):1263-1279.
[21] ERDOGAN B,WEBB DJ.Cancer-associated fibroblasts modulate growth factor signaling and extracellular matrix remodeling to regulate tumor metastasis[J].Biochem Soc Trans,2017,45(1):229-236.
[22]DE MARTINOD,BRAVO-CORDERO JJ.Collagens in cancer:Structural regulators and guardians of cancer progression[J].Cancer Res,2023,83(9):1386-1392.
[23] MASON JA,HAGEL KR,HAWK MA,et al.Metabolism during ECM detachment:Achilles heel of cancer cells[J].Trends Cancer,2017,3(7):475-481.
[24] HWANG HJ,OH MS,LEE DW,et al.Multiplex quantitative analysis of stroma-mediated cancer cell invasion,matrix remodeling,and drug response in a 3D co-culture model of pancreatic tumor spheroids and stellate cells[J].J Exp Clin Cancer Res,2019,38(1):258.
[25] MOHAN V,DAS A,SAGI I.Emerging roles of ECM remodeling processes in cancer[J].Semin Cancer Biol,2020,62:192-200.
[26]FLIES DB,LANGERMANN S,JENSEN C,et al.Regulation of tumor immunity and immunotherapy by the tumor collagen extracellular matrix[J].Front Immunol,2023,14:1199513.

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