Value of miR-2355-3p,miR-337-3p and miR-99a-5p detection in early screening of head and neck squamous cell carcinoma

  • LIU Jinghao ,
  • GUO Haiyan ,
  • GAN Guifang ,
  • CHEN Fuxiang
Expand
  • 1. Department of Clinical Laboratory, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Shanghai 200011, China
    2. College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine. Shanghai 200025, China

Received date: 2025-01-13

  Accepted date: 2025-04-02

  Online published: 2025-07-11

Abstract

Objective To explore the value of miR-2355-3p, miR-337-3p, and miR-99a-5p in the early screening of head and neck squamous cell carcinoma (HNSCC). Methods Serum samples and clinicopathological data were collected from 60 newly diagnosed HNSCC patients (HNSCC group) and 60 healthy individuals (normal control group) who visited the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between July 2023 and July 2024. The relative expression levels of miR-2355-3p, miR-337-3p, and miR-99a-5p were determined using parallel detection. The HNSCC screening and diagnostic efficacy of these three miRNAs was evaluated using receiver operating characteristic (ROC) curves. Results Compared with the normal control group, serum levels of miR-2355-3p and miR-337-3p were significantly upregulated in the HNSCC group (P<0.001), while miR-99a-5p was significantly downregulated (P=0.002). The expression levels of miR-2355-3p and miR-337-3p differed significantly among HNSCC patients with tumor size >2 cm versus ≤2 cm, clinical stage Ⅰ–Ⅱ versus stage Ⅲ–Ⅳ, and with versus without cervical lymph node metastasis (P<0.05). However, no significant differences in miRNA expression were found across different age or gender groups (P>0.05). The optimal cutoff values for diagnosing HNSCC were 0.0867 for miR-2355-3p, 0.1031 for miR-337-3p, and 0.1251 for miR-99a-5p, with corresponding areas under the curve (AUCs) of 0.892, 0.877, and 0.686, respectively. The combined detection of the three miRNAs yielded an AUC of 0.954, significantly higher than those of individual markers (P<0.05) and the combination of miR-2355-3p and miR-337-3p (AUC=0.898, P<0.05). The AUC for the combined detection in early-stage (stage Ⅰ–Ⅱ) HNSCC was 0.923. Conclusions miR-2355-3p and miR-337-3p are associated with the tumor stage, size, and lymph node metastasis of HNSCC. The combined detection of miR-2355-3p, miR-337-3p, and miR-99a-5p may serve as a potential method for early screening of HNSCC.

Cite this article

LIU Jinghao , GUO Haiyan , GAN Guifang , CHEN Fuxiang . Value of miR-2355-3p,miR-337-3p and miR-99a-5p detection in early screening of head and neck squamous cell carcinoma[J]. Journal of Diagnostics Concepts & Practice, 2025 , 24(02) : 204 -211 . DOI: 10.16150/j.1671-2870.2025.02.012

References

[1] BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. Ca-Cancer J Clin,2024,74(3):229-263.
[2] HAN B, ZHENG R, ZENG H, et al. Cancer incidence and mortality in China, 2022[J]. J Natl Cancer Ctr,2024,4(1):47-53.
[3] PAN X, XU X, WANG L, et al. BASP1 is a prognostic biomarker associated with immunotherapeutic response in head and neck squamous cell carcinoma[J]. Front Oncol, 2023,13:1021262.
[4] OLIVA M, SPREAFICO A, TABERNA M, et al. Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma[J]. Ann Oncol, 2019,30(1):57-67.
[5] KIM T, CROCE C M. MicroRNA: trends in clinical trials of cancer diagnosis and therapy strategies[J]. Exp Mol Med,2023,55(7):1314-1321.
[6] LEE Y S, DUTTA A. MicroRNAs in Cancer[J]. Annu Rev Pathol-Mech,2009,4(1):199-227.
[7] ZHAO Y, ZHANG W, YANG Y, et al. Diagnostic and prognostic value of microRNA-2355-3p and contribution to the progression in lung adenocarcinoma[J]. Bioengineered, 2021,12(1):4747-4756.
[8] MOHAMED F S, JALAL D, FADEL Y M, et al. Profiling of the serum MiRNAome in pediatric egyptian patients with wilms tumor[J]. Front Mol Biosci,2024,11:1453562.
[9] ZHUANG Q, SHEN J, CHEN Z, et al. MiR-337-3p suppresses the proliferation and metastasis of clear cell renal cell carcinoma cells via modulating Capn4[J]. Cancer Biomark,2018,23(4):515-525.
[10] ZUO X L, CHEN Z Q, WANG J F, et al. miR-337-3p suppresses the proliferation and invasion of hepatocellular carcinoma cells through targeting JAK2[J]. Am J Cancer Res, 2018,8(4):662-674.
[11] CAO X M. Role of miR-337-3p and its target Rap1A in modulating proliferation, invasion, migration and apoptosis of cervical cancer cells[J]. Cancer Biomark,2019,24(3):257-267.
[12] ZHANG R, LENG H, HUANG J, et al. miR-337 regulates the proliferation and invasion in pancreatic ductal adenocarcinoma by targeting HOXB7[J]. Diagn Pathol,2014,9(1):171.
[13] REGEV K, HEALY B C, PAUL A, et al. Identification of MS-specific serum miRNAs in an international multicenter study[J]. Neurol-Neuroimmunol,2018,5(5):e491.
[14] SAITO R, MARUYAMA S, KAWAGUCHI Y, et al. miR-99a-5p as Possible Diagnostic and Prognostic Marker in Patients With Gastric Cancer[J]. J Surg Res,2020,250:193-199.
[15] SUN X, YAN H. MicroRNA-99a-5p suppresses cell proli-feration, migration, and invasion by targeting isoprenylcysteine carboxylmethyltransferase in oral squamous cell carcinoma[J]. J Int Med Res,2021,49(5):0300060520939031.
[16] 武燃, 刘辉, 郑深, 等. MCU通过LETM1维持线粒体钙稳态调节口腔鳞状细胞癌细胞转移[J].重庆医科大学学报,2023,48(4):411-416.
  WU R, LIU H, ZHENG S, et al. MCU regulates metastasis of oral squamous cell carcinoma cells by maintaining mitochondrial calcium homeostasis through LETM1[J]. J Chong-qing Med Univ,2023,48(04):411-416.
[17] MASTRONIKOLIS N S, DELIDES A, KYRODIMOS E, et al. Insights into metastatic roadmap of head and neck cancer squamous cell carcinoma based on clinical, histopathological and molecular profiles[J]. Mol Biol Rep,2024,51(1):597.
[18] FORTERRE A, KOMURO H, AMINOVA S, et al. A Comprehensive Review of Cancer MicroRNA Therapeutic Delivery Strategies[J]. Cancers,2020,12(7):1852.
[19] MUNKER R, CALIN G A. MicroRNA profiling in cancer[J]. Clin Sci,2011,121(4):141-158.
[20] ALAHDAL M, ELKORD E. Non-coding RNAs in cancer immunotherapy: Predictive biomarkers and targets[J]. Clin Transl Med,2023,13(9):e1425.
[21] CHAKRABORTTY A, PATTON D J, SMITH B F, et al. miRNAs: potential as biomarkers and therapeutic targets for cancer[J]. Genes-Basel,2023,14(7):1375.
[22] HAO L, ZHANG Q, QIAO H Y, et al. TRIM29 alters bioe-nergetics of pancreatic cancer cells via cooperation of miR-2355-3p and DDX3X recruitment to AK4 transcript[J]. Mol Ther-Nucl Acids,2021,24:579-590.
[23] 陆开睿, 潘树矿, 胡梦甜,等. miR-2355-3p通过靶向SERPINA3增强口腔鳞状细胞癌细胞的放射敏感性[J].临床口腔医学杂志,2024,40(7):387-392.
  LU K R, PAN S K, HU M T, et al. miR-2355-3p enhances radiosensitivity of oral squamous cell carcinoma cells by targeting SERPINA3[J]. J Clin Stomatol,2024,40(7):387-392.
[24] DU L, SUBAUSTE M C, DESEVO C, et al. miR-337-3p and its targets STAT3 and RAP1A modulate taxane sensitivity in non-small cell lung cancers[J]. Plos One,2012,7(6):e39167.
[25] WANG Z, WANG J, YANG Y, et al. Loss of has-miR-337-3p expression is associated with lymph node metastasis of human gastric cancer[J]. J Exp Clin Canc Res,2013,32(1):76.
[26] TAMAI M, TATARANO S, OKAMURA S, et al. microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1[J]. Mol Oncol, 2022,16(6):1329-1346.
[27] CHEN Y, YAO J, QIN Y, et al. Biological role and clinical value of miR-99a-5p in head and neck squamous cell carcinoma ( HNSCC ): A bioinformatics-based study[J]. Febs Open Bio,2018,8(8):1280-1298.
[28] HUANG Q, SHEN Y J, HSUEH C Y, et al. Plasma extracellular vesicles-derived miR-99a-5p: A potential biomarker to predict early head and neck squamous cell carcinoma[J]. Pathol Oncol Res,2022,28:1610699.
[29] FEKETE J T, WELKER á, GY?RFFY B. miRNA expression signatures of therapy response in squamous cell carcinomas[J]. Cancers,2020,13(1):63.
[30] LUO H, YE Z. Identification of Serum miR-337-3p, miR-484, miR-582, and miR-3677 as promising biomarkers for osteosarcoma[J]. Clin Lab,2021,67(4).
[31] CHENG C, ZHANG H, DAI Z, et al. Circular RNA circVRK1 suppresses the proliferation, migration and invasion of osteosarcoma cells by regulating zinc finger protein ZNF652 expression via microRNA miR-337-3p[J]. Bioengineered,2021,12(1):5411-5427.
[32] PAN Y, LIU G, WANG D, et al. Analysis of lncRNA-mediated ceRNA crosstalk and identification of prognostic signature in head and neck squamous cell carcinoma[J]. Front Pharmacol,2019,10:150.
[33] ZHAO H, LI G, MA Q, et al. MicroRNA-99a-5p in circulating immune cells as a potential biomarker for the early diagnosis of ischemic stroke[J]. Brain Circ,2017,3(1):21.
[34] SASANO T, IHARA K, TANAKA T, et al. Risk stratification of atrial fibrillation and stroke using single nucleotide polymorphism and circulating biomarkers[J]. Plos One, 2023,18(10):e0292118.
[35] TOWLE R, DICKMAN C T D, MACLELLAN S A, et al. Identification of a serum-based microRNA signature that detects recurrent oral squamous cell carcinoma before it is clinically evident[J]. Brit J Cancer,2023,129(11):1810-1817.
[36] SHI J, BAO X, LIU Z, et al. Serum miR-626 and miR-5100 are promising prognosis predictors for oral squamous cell carcinoma[J]. Theranostics,2019,9(4):920-931.
[37] TORRES A, TORRES K, PESCI A, et al. Diagnostic and prognostic significance of miRNA signatures in tissues and plasma of endometrioid endometrial carcinoma patients[J]. Int J Cancer, 2013, 132(7): 1633-1645.
[38] SCHIFFMAN J D, FISHER P G, GIBBS P. Early detection of cancer: past, present, and future[J]. Am Soc of Cli Oncol Educ Book,2015(35):57-65.
[39] LAW H K W, YIM H C H. Early diagnosis of cancer using circulating microbial DNA[J]. Cell Rep Med,2024,5(4): 101502.
Outlines

/