We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Recent progress in biomarker-based diagnostics of Helicobacter pylori, gastric cancer-causing bacteria

    Kirti Saxena

    Amity Institute of Nanotechnology (AINT), Amity University Uttar Pradesh (AUUP), Sector 125, Noida, 201313, India

    ,
    Akanksha Deshwal

    Amity Institute of Nanotechnology (AINT), Amity University Uttar Pradesh (AUUP), Sector 125, Noida, 201313, India

    ,
    Ramesh Namdeo Pudake

    Amity Institute of Nanotechnology (AINT), Amity University Uttar Pradesh (AUUP), Sector 125, Noida, 201313, India

    ,
    Utkarsh Jain

    School of Health Sciences & Technology (SoHST), University of Petroleum & Energy Studies (UPES), Bidholi, Dehradun, 248007, India

    &
    Ravi Mani Tripathi

    *Author for correspondence: Tel.: +91 120 4392 128;

    E-mail Address: rmtripathi@amity.edu

    Amity Institute of Nanotechnology (AINT), Amity University Uttar Pradesh (AUUP), Sector 125, Noida, 201313, India

    Published Online:https://doi.org/10.2217/bmm-2023-0316

    The progression of any disease and its outcomes depend on the complicated interaction between pathogens, host and environmental factors. Thus, complete knowledge of bacterial toxins involved in pathogenesis is necessary to develop diagnostic methods and alternative therapies, including vaccines. This review summarizes recently employed biomarkers to diagnose the presence of Helicobacter pylori bacteria. The authors review distinct types of disease-associated biomarkers such as urease, DNA, miRNA, aptamers and bacteriophages that can be utilized as targets to detect Helicobacter pylori and, moreover, gastric cancer in its early stage. A detailed explanation is also given in the context of the recent utilization of these biomarkers in the development of a highly specific and sensitive biosensing platform.

    References

    • 1. Tripathi RM, Chung SJ. Phytosynthesis of palladium nanoclusters: an efficient nanozyme for ultrasensitive and selective detection of reactive oxygen species. Molecules 25(15), 3349 (2020).
    • 2. Tripathi RM, Pudake RN, Shrivastav BR, Shrivastav A. Antibacterial activity of poly (vinyl alcohol)–biogenic silver nanocomposite film for food packaging material. Adv. Nat. Sci. Nanosci. Nanotechnol. 9(2), 025020 (2018). https://iopscience.iop.org/article/10.1088/2043-6254/aac4ec/meta
    • 3. Mehrotra N, Tripathi RM. Short interfering RNA therapeutics: nanocarriers, prospects and limitations. IET Nanobiotechnol. 9(6), 386–395 (2015).
    • 4. Tripathi RM, Shrivastav BR, Shrivastav A. Antibacterial and catalytic activity of biogenic gold nanoparticles synthesised by Trichoderma harzianum. IET Nanobiotechnol. 12(4), 509–513 (2018).
    • 5. Claros J, Tocino RV, Fonseca E et al. Gastric cancer. Medicine 13, 1328–1334 (2021).
    • 6. Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag. Res. 10, 239 (2018).
    • 7. Polk DB, Peek RM. Helicobacter pylori: gastric cancer and beyond. Nat. Rev. Cancer 10(6), 403–414 (2010).
    • 8. Pucułek M, Machlowska J, Wierzbicki R, Baj J, Maciejewski R, Sitarz R. Helicobacter pylori associated factors in the development of gastric cancer with special reference to the early-onset subtype. Oncotarget 9(57), 31146–31162 (2018).
    • 9. Chauhan N, Tay ACY, Marshall BJ, Jain U. Helicobacter pylori VacA, a distinct toxin exerts diverse functionalities in numerous cells: an overview. Helicobacter 24(1), e12544 (2019).
    • 10. Ansari S, Yamaoka Y. Helicobacter pylori BabA in adaptation for gastric colonization. World J. Gastroenterol. 23(23), 4158–4169 (2017).
    • 11. Teymournejad O, Mobarez AM, Hassan ZM, Talebi Bezmin Abadi A. Binding of the Helicobacter pylori OipA causes apoptosis of host cells via modulation of Bax/Bcl-2 levels. Sci. Rep. 7(1), 1–8 (2017).
    • 12. Yamaoka Y, Ojo O, Fujimoto S et al. Helicobacter pylori outer membrane proteins and gastroduodenal disease. Gut 55(6), 775–781 (2006).
    • 13. Kienesberger S, Zechner EL. Helicobacter pylori. In: Encyclopedia of Microbiology. Academic Press, MA, USA (2019).
    • 14. Kao CY, Sheu BS, Wu JJ. Helicobacter pylori infection: an overview of bacterial virulence factors and pathogenesis. Biomedical Journal 39(1), 14–23 (2016).
    • 15. Hirschl AM, Makristathis A. Methods to detect Helicobacter pylori: from culture to molecular biology. Helicobacter 12, 6–11 (2007).
    • 16. Granstrom M, Lehours P, Bengtsson C, Mégraud F. Diagnosis of Helicobacter pylori. Helicobacter 13(Suppl. 1), 7–12 (2008).
    • 17. Mentis A, Lehours P, Mégraud F. Epidemiology and diagnosis of Helicobacter pylori infection. Helicobacter 20, 1–7 (2015).
    • 18. Cheng XJ, Lin JC, Tu SP. Etiology and prevention of gastric cancer. Gastrointest. Tumors 3(1), 25 (2016).
    • 19. Wang YK, Kuo FC, Liu CJ et al. Diagnosis of helicobacter pylori infection: current options and developments. World J. Gastroenterol. 21(40), 11221–11235 (2015).
    • 20. Rotimi O, Cairns A, Gray S, Moayyedi P, Dixon MF. Histological identification of Helicobacter pylori: comparison of staining methods. J. Clin. Pathol. 53(10), 756–759 (2000).
    • 21. Mobed A, Baradaran B, de la Guardia M et al. Advances in detection of fastidious bacteria: from microscopic observation to molecular biosensors. Trends Anal. Chem. 113, 157–171 (2019).
    • 22. Jain U, Saxena K. Smart nanobiosensors. In: Nanosensors for Smart Manufacturing. Elsevier, 231–245 (2021).
    • 23. Nosrati R, Golichenari B, Nezami A et al. Helicobacter pylori point-of-care diagnosis: nano-scale biosensors and microfluidic systems. Trends Anal. Chem. 97, 428–444 (2017).
    • 24. Saxena K, Chauhan N, Jain U. Advances in diagnosis of Helicobacter pylori through biosensors: point of care devices. Anal. Biochem. 630, 114325 (2021).
    • 25. Waskito LA, Salama NR, Yamaoka Y. Pathogenesis of Helicobacter pylori infection. Helicobacter 23, e12516 (2018).
    • 26. Marshall BJ. One hundred years of discovery and rediscovery of Helicobacter pylori and its association with peptic ulcer disease. Helicobacter pylori: physiology and genetics Wiley Online Library, 19–24 (2001).
    • 27. Bimczok D, Müller A, Smith PD. Helicobacter pylori infection. In: Principle of Mucosal Immunology. Taylor and Francis, Garland Science, 415–426 (2020).
    • 28. Sankararaman S, Moosavi L. Urea Breath Test. In: InStatPearls. StatPearls Publishing, 135–143 (2021).
    • 29. Dechant FX, Dechant R, Kandulski A et al. Accuracy of different rapid urease tests in comparison with histopathology in patients with endoscopic signs of gastritis. Digestion 101(2), 184–190 (2020).
    • 30. Alzoubi H, Al-Mnayyis A, Al Rfoa I et al. The use of 13C-Urea Breath Test for non-invasive diagnosis of Helicobacter pylori infection in comparison to endoscopy and stool antigen test. Diagnostics 10(7), 448 (2020).
    • 31. Zhang L, Cao D, Tang T, Zuo Z, Huang J, Duan L. A label-free fluorescence method for detection of ureC gene and diagnosis of Helicobacter pylori infection. Luminescence 33(5), 941–946 (2018).
    • 32. Xiao S, Shang K, Li W, Wang X. An efficient biosensor based on the synergistic catalysis of Helicobacter pylori urease b subunit and nanoplatinum for urease inhibitors screening and antagonistic mechanism analyzing. Sens. Actuators B Chem. 355, 131284 (2022).
    • 33. Shahrashoob M, Mohsenifar A, Tabatabaei M et al. Detection of Helicobacter pylori genome with an optical biosensor based on hybridization of urease gene with a gold nanoparticles-labeled probe. J. Appl. Spectrosc. 83, 322–329 (2016).
    • 34. Xu C, Soyfoo DM, Wu Y, Xu S. Virulence of Helicobacter pylori outer membrane proteins: an updated review. Eur. J. Clin. Microbiol. Infect. Dis. 39(10), 1821–1830 (2020).
    • 35. Kim A, Servetas SL, Kang J et al. Helicobacter pylori outer membrane protein, HomC, shows geographic dependent polymorphism that is influenced by the Bab family. J. Microbiol. 54(12), 846–852 (2016).
    • 36. Gupta S, Jain U, Murti BT, Putri AD, Tiwari A, Chauhan N. Nanohybrid-based immunosensor prepared for Helicobacter pylori BabA antigen detection through immobilized antibody assembly with @ Pd nano/rGO/PEDOT sensing platform. Sci. Rep. 10(1), 21217 (2020).
    • 37. Xiao S, Shang K, Zhang L, Li W, Wang X. A rapid anti-Helicobacter pylori biofilm drug screening biosensor based on AlpB outer membrane protein and colloidal gold/nanoporous gold framework. Biosens. Bioelectron. 215, 114599 (2022).
    • 38. Kalali B, Mejías-Luque R, Javaheri A, Gerhard M. H. pylori virulence factors: influence on immune system and pathology. Mediators Inflamm. 2014, 426309 (2014).
    • 39. Gupta S, Tiwari A, Jain U, Chauhan N. Synergistic effect of 2D material coated Pt nanoparticles with PEDOT polymer on electrode surface interface for a sensitive label free Helicobacter pylori CagA(Ag-Ab) immunosensing. Mater. Sci. Eng. C 103, 109733 (2019).
    • 40. Jain U, Gupta S, Soni S, Khurana MP, Chauhan N. Triple-nanostructuring-based noninvasive electro-immune sensing of CagA toxin for Helicobacter pylori detection. Helicobacter 25(4), 1–11 (2020).
    • 41. Chauhan N, Gupta S, Avasthi DK, Adelung R, Mishra YK, Jain U. Zinc oxide tetrapods based biohybrid interface for voltammetric sensing of Helicobacter pylori. ACS Appl. Mater. Interfaces 10(36), 30631–30639 (2018).
    • 42. Saxena K, Kumar A, Chauhan N, Khanuja M, Malhotra BD, Jain U. Electrochemical immunosensor for detection of H. pylori secretory protein VacA on g-C3N4/ZnO nanocomposite-modified au electrode. ACS Omega 7(36), 32292–32301 (2022).
    • 43. Saxena K, Chauhan N, Malhotra BD, Jain U. A molecularly imprinted polymer-based electrochemical biosensor for detection of VacA virulence factor of H. pylori causing gastric cancer. Process Biochem. 130, 87–95 (2023).
    • 44. Saxena K, Murti BT, Yang PK, Malhotra BD, Chauhan N, Jain U. Fabrication of a molecularly imprinted nano-interface-based electrochemical biosensor for the detection of CagA virulence factors of H. pylori. Biosensors 12(12), 1066 (2022).
    • 45. Asadzadeh-Firouzabadi A, Zare HR. An electrochemical nanogenosensor for label based and label free detection of H. pylori cagE gene and evaluation of DNA damage induced by UVC radiation. J. Electrochem. Soc. 164(2), B1–B9 (2017).
    • 46. Asadzadeh-Firouzabadi A, Zare HR, Nasirizadeh N. Electrochemical biosensor for detection of target DNA sequence and single-base mismatch related to Helicobacter pylori using chlorogenic acid as hybridization indicator. J. Electrochem. Soc. 163, B43 (2016).
    • 47. Wang L, Cui K, Wang P, Pei M, Guo W. A sensitive electrochemical DNA sensor for detecting Helicobacter pylori based on accordion-like Ti3C2Tx: a simple strategy. Anal. Bioanal. Chem. 413(16), 4353–4362 (2021).
    • 48. Del Pozo MV, Alonso C, Pariente F, Lorenzo E. DNA biosensor for detection of Helicobacter pylori using phen-dione as the electrochemically active ligand in osmium complexes. Anal. Chem. 77(8), 2550–2557 (2005).
    • 49. Lv MM, Fan SF, Wang QL, Lv QY, Song X, Cui HF. An enzyme-free electrochemical sandwich DNA assay based on the use of hybridization chain reaction and gold nanoparticles: application to the determination of the DNA of Helicobacter pylori. Microchim. Acta 187, 73 (2020).
    • 50. Shanehsaz M, Mohsenifar A, Hasannia S, Pirooznia N, Samaei Y, Shamsipur M. Detection of Helicobacter pylori with a nanobiosensor based on fluorescence resonance energy transfer using CdTe quantum dots. Microchim. Acta 180, 195–202 (2013).
    • 51. Zhang W, Liu QX, Guo ZH, Lin JS. Practical application of aptamer-based biosensors in detection of low molecular weight pollutants in water sources. Molecules 23(2), 344 (2018).
    • 52. Yadav AK, Verma D, Chaudhary N, Kumar A, Solanki PR. Aptamer based switches: a futuristic approach for Helicobacter pylori detection. Mater. Lett. 308, 131239 (2022).
    • 53. Wu H, Gu L, Ma X et al. Rapid detection of Helicobacter pylori by the naked eye using DNA aptamers. ACS Omega 6(5), 3771–3779 (2021).
    • 54. Yan W, Gu L, Ren W et al. Recognition of Helicobacter pylori by protein-targeting aptamers. Helicobacter 24(3), e12577 (2019).
    • 55. Zou H, Lin C, Zan H et al. A novel fluorescent aptasensor for ultrasensitive detection of Helicobacter pylori in stool samples based on catalytic hairpin assembly cascade hybridization chain reaction. Sens. Actuators B Chem. 368, 132157 (2022).
    • 56. Roushani M, Sarabaegi M, Hosseini H, Pourahmad F. Gold nanostructures integrated on hollow carbon N-doped nanocapsules as a novel high-performance aptasensing platform for Helicobacter pylori detection. J. Mater. Sci. 57(1), 589–597 (2022).
    • 57. Wang Z, Wang H, Cheng X et al. Aptamer-superparamagnetic nanoparticles capture coupling siderophore-Fe3+ scavenging actuated with carbon dots to confer an “off-on” mechanism for the ultrasensitive detection of Helicobacter pylori. Biosens. Bioelectron. 193, 113551 (2021).
    • 58. Fei Y, Fang R, Xiao L et al. The development of a colorimetric biosensing assay for the detection of Helicobacter pylori in feces. Anal. Biochem. 651, 114737 (2022).
    • 59. Isaka Y. DNAzymes as potential therapeutic molecules. Curr. Opin. Mol. Ther. 9(2), 132–136 (2007).
    • 60. Khan S, Burciu B, Filipe CDM, Li Y, Dellinger K, Didar TF. DNAzyme-based biosensors: immobilization strategies, applications, and future prospective. ACS Nano 15(9), 13943–13969 (2021).
    • 61. Ali MM, Wolfe M, Tram K et al. A DNAzyme-based colorimetric paper sensor for Helicobacter pylori. Angew. Chemie Int. Ed. 131(29), 10012–10016 (2019).
    • 62. Liu Z, Yao C, Wang Y, Zheng W. Visual diagnostic of Helicobacter pylori based on a cascade amplification of PCR and G-quadruplex DNAzyme as a color label. J. Microbiol. Methods 146, 46–50 (2018).
    • 63. Butcher LD, den Hartog G, Ernst PB, Crowe SE. Oxidative stress resulting from Helicobacter pylori infection contributes to gastric carcinogenesis. Cell. Mol. Gastroenterol. Hepatol. 3(3), 316–322 (2017).
    • 64. Jain U, Saxena K, Chauhan N. Helicobacter pylori induced reactive oxygen Species: a new and developing platform for detection. Helicobacter 26(3), e12796 (2021).
    • 65. Hahm KB, Lee KJ, Kim JH, Cho SW, Chung MH. Helicobacter pylori infection, oxidative DNA damage, gastric carcinogenesis, and reversibility by rebamipide. Dig. Dis. Sci. 43(Suppl. 9), S72–S77 (1998).
    • 66. Raza Y, Khan A, Farooqui A et al. Oxidative DNA damage as a potential early biomarker of Helicobacter pylori associated carcinogenesis. Pathol. Oncol. Res. 20(4), 839–846 (2014).
    • 67. Parizadeh SM, Jafarzadeh-Esfehani R, Avan A, Ghandehari M, Goldani F, Parizadeh SM. The prognostic and predictive value of microRNAs in patients with H. pylori-positive gastric cancer. Curr. Pharm. Des. 24(39), 4639–4645 (2018).
    • 68. Yu J, Xu Q, Zhang X, Zhu M. Circulating microRNA signatures serve as potential diagnostic biomarkers for Helicobacter pylori infection. J. Cell. Biochem. 120(2), 1735–1741 (2018).
    • 69. Yang J, Song H, Cao K, Song J, Zhou J. Comprehensive analysis of Helicobacter pylori infection-associated diseases based on miRNA-mRNA interaction network. Brief. Bioinform. 20(4), 1492–1501 (2019).
    • 70. Mahboobi R, Fallah F, Yadegar A et al. Expression analysis of miRNA-155 level in Helicobacter pylori related inflammation and chronic gastritis. Iran. J. Microbiol. 14(4), 495 (2022).
    • 71. Khayam N, Nejad HR, Ashrafi F, Abolhassani M. Expression profile of miRNA-17-3p and miRNA-17-5p genes in gastric cancer patients with Helicobacter pylori infection. J. Gastrointest. Cancer 52, 130–137 (2021).
    • 72. Iwasaki H, Shimura T, Yamada T et al. A novel urinary microRNA biomarker panel for detecting gastric cancer. J. Gastroenterol. 54(12), 1061–1069 (2019).
    • 73. Stransky B, de Souza SJ. Gene expression biomarkers. Encyclopedia of Systems Biology Springer, NY, USA, 791–792 (2013).
    • 74. Segundo-Val IS, Sanz-Lozano CS. Introduction to the gene expression analysis. Methods Mol. Biol. 1434, 29–43 (2016).
    • 75. Sun H. Identification of key genes associated with gastric cancer based on DNA microarray data. Oncol. Lett. 11(1), 525–530 (2016).
    • 76. McLean MH, El-Omar EM. Genetics of gastric cancer. Nat. Rev. Gastroenterol. Hepatol. 11(11), 664–674 (2014).
    • 77. Yang T, Zeng H, Chen W et al. Helicobacter pylori infection, H19 and LINC00152 expression in serum and risk of gastric cancer in a Chinese population. Cancer Epidemiol. 44, 147–153 (2016).
    • 78. Fattahi S, Kosari-Monfared M, Golpour M et al. LncRNAs as potential diagnostic and prognostic biomarkers in gastric cancer: a novel approach to personalized medicine. J. Cell. Physiol. 235(4), 3189–3206 (2020).
    • 79. Li N, Ouyang Y, Chen S et al. Integrative analysis of differential lncRNA/mRNA expression profiling in Helicobacter pylori infection-associated gastric carcinogenesis. Front. Microbiol. 11, 880 (2020).
    • 80. Rajabi A, Riahi A, Shirabadi-Arani H, Moaddab Y, Haghi M, Safaralizadeh R. Overexpression of HOXA-AS2 lncRNA in patients with gastric cancer and its association with Helicobacter pylori infection. J. Gastrointest. Cancer 53(1), 72–77 (2022).
    • 81. Pérez-Rodríguez M, Partida-Rodríguez O, Camorlinga-Ponce M et al. Polymorphisms in HLA-DQ genes, together with age, sex, and Helicobacter pylori infection, as potential biomarkers for the early diagnosis of gastric cancer. Helicobacter 22(1), e12326 (2017).
    • 82. Gao J, Yu T, Xuan Y, Zhu Z. High expression of GNB4 predicts poor prognosis in patients with Helicobacter pylori-positive advanced gastric cancer. Transl. Cancer Res. 9(7), 4224 (2020).
    • 83. Liu D, Ma X, Yang F, Xiao D, Jia Y, Wang Y. Discovery and validation of methylated-differentially expressed genes in Helicobacter pylori-induced gastric cancer. Cancer Gene Ther. 27(6), 473–485 (2020).
    • 84. Ding W, Jiang H, Ye N et al. Identification and analysis of crucial genes in H. pylori-associated gastric cancer using an integrated bioinformatics approach. J. Oncol. 1, 2023 (2023).