Biomarkers in Gastric Cancer: Pioneering Advances in Diagnosis, Personalized Treatment Strategies, and Screening for Improved Patient Prognosis

*Dr. Ummed kumar, ¹Juhi Rawal
*Researcher Scientist, Aligarh College of Pharmacy
¹Research Scholar, Aligarh College of Pharmacy

Article Details

Title: Biomarkers in Gastric Cancer: Pioneering Advances in Diagnosis, Personalized Treatment Strategies, and Screening for Improved Patient Prognosis

Authors: Dr. Ummed Kumar, Juhi Rawa

Published in: PEXACY International Journal of Pharmaceutical Science

Volume/Issue: 2(12)

Pages: 167-185

Publication Date: 09/12/2023

DOI: 10.5281/zenodo.10314129

ISSN: 2584-024X

Language: English

Publisher: PEXACY International Journal of Pharmaceutical Science

PDF Download: Access Full Paper

Abstract: Biomarkers in Gastric Cancer: This review focus into the recent advancements in the identification and application of biomarkers for gastric cancer, exploring their pivotal role in enhancing early diagnosis, prognosis, and the development of personalized treatment strategies. This review synthesizes recent advancements in understanding the molecular pathogenesis of gastric cancer, which involves a myriad of genetic, epigenetic, and environmental factors, including Helicobacter pylori infection. Novel biomarkers such as lncRNAs, circRNAs, and exosomal RNAs have emerged as potential tools for early diagnosis and prognosis. The review also highlights the revolution in gastric cancer treatment brought about by personalized medicine, particularly through immunotherapy and genomic profiling. Additionally, it discusses the shift in prevention strategies towards H. pylori eradication and risk stratification, and the development of novel diagnostic methods offering potential for non-invasive and accurate detection. The evolving landscape of gastric cancer research underscores the importance of a multifaceted approach that encompasses molecular biology, personalized therapy, and prevention strategies. The review emphasizes the necessity of continued research and innovation for translating these findings into clinical practice and improving patient outcomes globally.

Keywords: Gastric Cancer, Molecular Mechanisms, Biomarkers, Helicobacter pylori, Genomic Profiling, Early Detection, lncRNAs, circRNAs, Exosomal RNAs, Prevention Strategies, Screening Programs, Therapeutic Targets, Non-invasive Diagnosis.

Article can be accessed online on: PEXACY International Journal of Pharmaceutical Science
DOI: 10.5281/zenodo.10314129
Corresponding Author- *Dr. Ummed kumar
Update: Received on 05/11/2023; Accepted; 07/12/2023, Published on; 09/12/2023

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Cite As: kumar, U., & Rawal, J. (2023). Biomarkers in Gastric Cancer: Pioneering Advances in Diagnosis, Personalized Treatment Strategies, and Screening for Improved Patient Prognosis. PEXACY International Journal of Pharmaceutical Science, 2(12), 167–185. https://doi.org/10.5281/zenodo.10314129

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INTRODUCTION TO BIOMARKERS IN GASTRIC CANCER

Gastric cancer remains a significant global health challenge, ranking as the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. The complexity and heterogeneity of gastric cancer necessitate the identification and utilization of biomarkers for early detection, prognosis, and personalized therapeutic strategies. Biomarkers in gastric cancer encompass a broad range of biological molecules that are indicative of the pathophysiological state of the disease.

Recent advancements in molecular biology and bioinformatics have led to the discovery of numerous potential biomarkers. These biomarkers include genetic, epigenetic, proteomic, and metabolomic signatures that can provide critical insights into the molecular mechanisms underlying gastric cancer development and progression. For instance, Röcken (2023) emphasizes the importance of predictive biomarkers in gastric cancer, highlighting their role in guiding therapeutic decisions and improving patient outcomes. Similarly, Szász et al. (2016) underscore the significance of survival-associated biomarkers, validated through transcriptomic data of over a thousand patients, in understanding the prognosis of gastric cancer.

The integration of bioinformatic analysis has been pivotal in identifying and verifying potential biomarkers. Sun et al. (2022) demonstrate this approach by integrating bioinformatic analysis for the identification of biomarkers in gastric cancer. Furthermore, Xie et al. (2022) developed a web portal, OSgc, to assess the performance of prognostic biomarkers in gastric cancer, showcasing the utility of digital tools in biomarker research.

Long non-coding RNAs (lncRNAs) have also emerged as potential diagnostic and prognostic biomarkers. Fattahi et al. (2020) discuss the role of lncRNAs in gastric cancer, proposing a novel approach to personalized medicine. Additionally, Liu et al. (2021) conducted a comprehensive analysis of insulin-like growth factor-binding proteins (IGFBPs) as biomarkers in gastric cancer, further expanding the biomarker repertoire.

The critical review of current and potential biomarkers by de Mello et al. (2021) provides a comprehensive overview of the landscape of biomarkers in gastric cancer. Similarly, novel prognostic biomarkers such as CGB5, MKNK2, and PAPPA2 have been identified by Qin et al. (2021), offering new avenues for research and clinical application.

Yuan et al. (2022) focused on platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patients, highlighting the intersection of biomarker research and immune response. Lastly, the study by Liu et al. (2021) on macrophage M2 infiltration in gastric cancer identifies potential prognostic biomarkers associated with the tumor microenvironment.

In conclusion, the exploration of biomarkers in gastric cancer is a rapidly evolving field, offering promising avenues for early detection, prognosis, and personalized treatment strategies. The integration of molecular biology, bioinformatics, and clinical research continues to unveil new biomarkers, enhancing our understanding and management of gastric cancer.

MOLECULAR MECHANISMS OF GASTRIC CANCER

Understanding the molecular mechanisms underlying gastric cancer is crucial for developing effective diagnostic and therapeutic strategies. Gastric cancer is a multifactorial disease influenced by genetic, epigenetic, and environmental factors. The molecular pathogenesis of gastric cancer involves various pathways and mechanisms, including genetic mutations, epigenetic alterations, dysregulation of non-coding RNAs, and aberrant signaling pathways.

One of the key factors in the initiation and progression of gastric cancer is the infection with Helicobacter pylori. Servetas et al. (2016) discuss the molecular mechanisms of gastric cancer initiation and progression by H. pylori, highlighting the bacterium’s role in inducing genetic and epigenetic changes that contribute to gastric carcinogenesis. Additionally, the differences in prognosis among gastric cancer patients of different sexes and races, as well as the molecular mechanisms involved, are explored by H. Li et al. (2019), indicating the influence of genetic diversity and environmental factors on the disease’s pathogenesis.

Long non-coding RNAs (lncRNAs) have been identified as critical regulators in gastric cancer. T. Li et al. (2016) delve into the molecular mechanisms of lncRNAs in gastric cancer, revealing their role in gene regulation and their potential as therapeutic targets. The molecular mechanisms of peritoneal dissemination in gastric cancer, a major route of metastasis, are elaborated by Kanda & Kodera (2016), providing insights into the complex process of cancer cell invasion and metastasis.

Chemoresistance is a significant challenge in the treatment of gastric cancer. Shi & Gao (2016) discuss the molecular mechanisms of chemoresistance in gastric cancer, shedding light on the genetic and epigenetic changes that contribute to the resistance to chemotherapy. The role of microRNAs (miRNAs) in drug resistance and their theranostic potential are explored by Yang et al. (2017), emphasizing the importance of miRNAs in the modulation of drug response and as potential biomarkers.

Nuclear magnetic resonance-based tissue metabolomic analysis has been used to clarify the molecular mechanisms of gastric carcinogenesis. Gu et al. (2020) demonstrate how metabolomic profiling can provide insights into the metabolic alterations associated with gastric cancer. The lncRNA SMARCC2/miR-551b-3p/TMPRSS4 axis in gastric cancer, as investigated by Yuan et al. (2018), represents a novel molecular mechanism that contributes to the disease’s progression.

Tetraspanins, a family of membrane proteins, have been identified as novel molecular regulators of gastric cancer. Deng et al. (2021) discuss the role of tetraspanins in gastric cancer, highlighting their involvement in cell adhesion, migration, and signaling. Lastly, the inverse association between Bmi-1 and RKIP, affecting the clinical outcome of gastric cancer and revealing potential molecular mechanisms underlying tumor metastasis and chemotherapy resistance, is presented by Chen et al. (2016).

In summary, the molecular mechanisms of gastric cancer are diverse and complex, involving a multitude of genetic, epigenetic, and environmental factors. Understanding these mechanisms is essential for the development of targeted therapies and improving patient outcomes.

THERAPEUTIC STRATEGIES IN GASTRIC CANCER

The therapeutic landscape of gastric cancer has evolved significantly over the years, with a shift towards more personalized and targeted approaches. The complexity of gastric cancer, characterized by its heterogeneity and varied molecular profiles, necessitates a multifaceted approach to therapy, encompassing surgery, chemotherapy, targeted therapy, immunotherapy, and novel pharmacological interventions.

Surgical resection remains the cornerstone of curative treatment for gastric cancer. Wong et al. (2003) discuss various therapeutic strategies in gastric cancer, emphasizing the role of surgery in early-stage disease. However, the majority of patients present with advanced disease, requiring a combination of systemic therapies.

The emergence of immunotherapy has revolutionized the treatment landscape for gastric cancer. Ma et al. (2022) explore immune evasion mechanisms and therapeutic strategies in gastric cancer, highlighting the potential of immunotherapies in overcoming tumor immune escape. The integration of genomic biology into therapeutic strategies, particularly for gastric cancer peritoneal metastasis, is discussed by Gwee et al. (2022), illustrating the importance of personalized medicine based on genomic profiling.

Autophagy, a cellular degradation process, has been identified as a potential therapeutic target in gastric cancer. Rahman et al. (2021) delve into the potential therapeutic action of autophagy in gastric cancer management, suggesting novel treatment strategies and pharmacological interventions that target this pathway.

Proteomic characterization has also been instrumental in understanding the response of gastric cancer to chemotherapy and targeted therapy. Li et al. (2022) demonstrate how proteomic analysis can reveal new therapeutic strategies and improve the efficacy of existing treatments. Personalized therapeutic strategies in HER2-driven gastric cancer are discussed by Ughetto et al. (2021), emphasizing the importance of molecular characterization in guiding therapy selection.

The role of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in gastric cancer and its potential as a therapeutic target is explored by Farkhondeh et al. (2021). Targeting this pathway could offer new avenues for treatment, particularly in overcoming drug resistance. Zhao et al. (2022) focus on therapeutic strategies targeting immune cells in gastric cancer, providing insights into future directions for immunotherapy.

Seeneevassen et al. (2021) provide a comprehensive overview of advances in carcinogenesis research and new therapeutic strategies in gastric cancer, highlighting the rapid progress in understanding the disease’s biology and translating this knowledge into clinical practice. Finally, Ji et al. (2022) discuss a prognostic gene-based signature that can identify subgroups of gastric cancer patients with different clinical outcomes and therapeutic needs, underscoring the move towards precision oncology.

In conclusion, the therapeutic strategies in gastric cancer are diverse and continually evolving, with a growing emphasis on personalized medicine and targeted therapies. Understanding the molecular and cellular mechanisms of gastric cancer is key to developing effective treatments and improving patient outcomes.

GASTRIC CANCER PREVENTION AND SCREENING

The prevention and early detection of gastric cancer are critical components in reducing the global burden of this disease. Gastric cancer prevention strategies primarily focus on identifying and mitigating risk factors, including Helicobacter pylori infection, dietary factors, and genetic predispositions. Screening programs aim to detect gastric cancer at an early stage, where treatment is more likely to be successful.

The role of real-world practice in gastric cancer prevention and screening, particularly the need for practical prediction models, is highlighted by He et al. (2023). These models can help identify high-risk individuals and guide targeted screening efforts. Hamashima (2022) discusses the forthcoming steps in gastric cancer prevention, exploring how risk stratification can be combined with endoscopic screening to enhance the effectiveness of early detection programs.

A paradigm shift in gastric cancer prevention from endoscopic screening to Helicobacter pylori eradication is proposed by Kim & Choi (2022), especially in regions like Korea where gastric cancer prevalence is high. This approach aligns with the Taipei global consensus on screening and eradication of H. pylori for gastric cancer prevention, as outlined by Liou et al. (2020). The consensus emphasizes the importance of a comprehensive approach that includes both screening and treatment of H. pylori infection.

Chiang et al. (2022) advocate for mass screening and eradication of H. pylori as policy recommendations for gastric cancer prevention, particularly in high-risk populations. The cost-effectiveness of screening for H. pylori in the context of gastric cancer prevention is analyzed by Tumanbaev et al. (2022) and Sarmasti et al. (2022), providing insights into the economic feasibility of such programs.

The clinical value of pepsinogen in the screening, prevention, and diagnosis of gastric cancer is explored by Han et al. (2022). Pepsinogen levels can serve as a biomarker for gastric mucosal health and cancer risk, offering a non-invasive screening option. Lim (2021) also emphasizes the importance of screening and eradication of H. pylori for gastric cancer prevention, reinforcing the global consensus on this strategy.

Finally, Wang et al. (2022) present a decision analysis on the effect, affordability, and cost-effectiveness optimization of nationwide gastric cancer prevention in China, a country with a high incidence of gastric cancer. This study provides a model for other countries to develop and implement effective gastric cancer prevention strategies.

In conclusion, gastric cancer prevention and screening are evolving fields, with a growing emphasis on risk stratification, H. pylori eradication, and cost-effective screening methods. These strategies hold the promise of reducing the incidence and mortality of gastric cancer globally.

NOVEL DIAGNOSTIC METHODS IN GASTRIC CANCER

The development of novel diagnostic methods in gastric cancer is crucial for early detection and improved patient outcomes. Recent advancements in molecular biology and technology have led to the discovery of various biomarkers and techniques that offer potential for non-invasive, sensitive, and specific diagnosis of gastric cancer.

RPP30 has been identified as a novel diagnostic and prognostic biomarker for gastric cancer. Kan et al. (2022) discuss the significance of RPP30, highlighting its potential in improving the accuracy of gastric cancer diagnosis. Similarly, Huang et al. (2021) elucidate the role of serum tRF-31-U5YKFN8DYDZDD as a novel diagnostic biomarker in gastric cancer, offering insights into the molecular mechanisms of the disease.

Long non-coding RNAs (lncRNAs) have emerged as significant biomarkers in gastric cancer. Chen et al. (2021) report that lncRNA-HEIH is a novel diagnostic and predictive biomarker, providing a new avenue for non-invasive diagnosis. The role of HKDC1 in gastric cancer as a new diagnostic, prognostic biomarker, and novel therapeutic target is explored by Hu et al. (2023), further expanding the biomarker repertoire.

Circulating exosomal long non-coding RNA H19 has been identified by Zhou et al. (2020) as a potential novel diagnostic and prognostic biomarker for gastric cancer. This discovery underscores the importance of exosomal RNAs in cancer diagnostics. CircRNA CDR1as is another novel diagnostic and prognostic biomarker for gastric cancer, as presented by Li et al. (2023), demonstrating the emerging role of circular RNAs in cancer biology.

Wang et al. (2023) introduce circRNA circSLIT2 as a novel diagnostic and prognostic biomarker for gastric cancer. This finding highlights the potential of circRNAs as biomarkers in gastric cancer. Plasma exosomal long noncoding RNA lnc-SLC2A12-10:1 has been proposed by Zheng et al. (2020) as a novel diagnostic biomarker for gastric cancer, further emphasizing the role of exosomal RNAs in the disease.

Xu et al. (2020) provide a comprehensive assessment of plasma circ_0004771 as a novel diagnostic and dynamic monitoring biomarker in gastric cancer. This study suggests the utility of circulating RNAs in monitoring disease progression. Lastly, Cheng et al. (2020) identify circulating miR-19a-3p and miR-483-5p as novel diagnostic biomarkers for the early diagnosis of gastric cancer, offering a potential for early detection through blood-based biomarkers.

In conclusion, novel diagnostic methods in gastric cancer, particularly those based on molecular biomarkers such as lncRNAs, circRNAs, and exosomal RNAs, are showing promising results. These advancements hold the potential to revolutionize gastric cancer diagnostics, enabling earlier detection and more effective treatment strategies.

DISCUSSION

The exploration of gastric cancer, from its molecular mechanisms to novel diagnostic methods, presents a comprehensive understanding of this complex and lethal disease. The integration of advanced molecular biology techniques and bioinformatics has significantly contributed to the identification of novel biomarkers and therapeutic targets, paving the way for more effective and personalized treatment strategies.

Molecular Mechanisms and Biomarkers

The molecular mechanisms underlying gastric cancer involve a myriad of genetic, epigenetic, and environmental factors. The role of Helicobacter pylori infection in gastric carcinogenesis, as discussed by Servetas et al. (2016), highlights the importance of understanding pathogen-host interactions. The emergence of lncRNAs and circRNAs as potential diagnostic and prognostic biomarkers, as reported by Fattahi et al. (2020) and Li et al. (2023), respectively, underscores the complexity of gastric cancer’s molecular landscape. These discoveries not only enhance our understanding of the disease’s pathophysiology but also open new avenues for targeted therapies.

Therapeutic Strategies

The shift towards personalized medicine in gastric cancer treatment is evident in the current therapeutic landscape. The role of immunotherapy, as explored by Ma et al. (2022), and the importance of genomic profiling in guiding treatment, as discussed by Gwee et al. (2022), are indicative of a more tailored approach to cancer treatment. The potential of autophagy as a therapeutic target, highlighted by Rahman et al. (2021), and the exploration of Nrf2 pathway by Farkhondeh et al. (2021) further illustrate the diverse and evolving nature of gastric cancer therapeutics.

Prevention and Screening

Prevention and early detection remain key in reducing gastric cancer mortality. The emphasis on H. pylori eradication, as advocated by Kim & Choi (2022) and Liou et al. (2020), reflects a shift in prevention strategies. The economic feasibility of such programs, analyzed by Tumanbaev et al. (2022) and Sarmasti et al. (2022), is crucial for their implementation on a larger scale. The use of biomarkers like pepsinogen, as discussed by Han et al. (2022), in screening programs, offers a non-invasive method for early detection.

Novel Diagnostic Methods

The development of novel diagnostic methods, such as those based on circulating exosomal RNAs and circRNAs, represents a significant advancement in the early detection of gastric cancer. The studies by Zhou et al. (2020) and Wang et al. (2023) on exosomal RNAs, and the comprehensive assessment of plasma circ_0004771 by Xu et al. (2020), demonstrate the potential of these biomarkers in improving diagnostic accuracy and patient monitoring.

CONCLUSION

The advancements in understanding the molecular mechanisms, development of novel diagnostic methods, and the evolution of therapeutic strategies in gastric cancer are promising. However, challenges remain, particularly in translating these findings into clinical practice and ensuring equitable access to these advancements globally. Continued research, coupled with an emphasis on prevention and early detection, is essential for improving the prognosis and quality of life for patients with gastric cancer.

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