Divide and conquer: subproteomic approaches toward gastric cancer biomarker and drug target discovery

Lin, Fan; Tan, Hock Jin; Guan, Jye Swei; Lim, Yoon Pin

doi:10.1586/14789450.2014.904751

Cited by 5 publications

(4 citation statements)

References 114 publications

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“…Fourth, some of the studies had a case-control design, which may be prone to overstating the accuracy of a diagnostic trial [ 66 ]. Fifth, even though increasing the detection rate of early GC could improve the overall prognosis[ 67 ], only 2 studies in the present analysis focused on the early detection of GC. There is a great need to conduct clinical trials to better identify the validity of SPG in the early detection of GC in the future.…”

Section: Discussionmentioning

confidence: 99%

Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis

et al. 2015

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BackgroundHuman pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection.MethodsWe searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I2 statistics and publication bias was assessed using Begg and Mazumdar’s test. Meta-regression and subgroup analyses were performed to explore study heterogeneity.ResultsIn total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60–0.76), 0.73 (95% CI: 0.62–0.82), 2.57 (95% CI: 1.82–3.62), and 0.43 (95% CI: 0.34–0.54), 0.76 (95% CI: 0.72–0.80) and 6.01 (95% CI: 3.69–9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55–0.80), 0.88 (95% CI: 0.77–0.94), 5.80 (95% CI: 3.06–10.99), and 0.35 (95% CI: 0.24–0.51), 0.85 (95% CI: 0.82–0.88) and 16.50 (95% CI: 8.18–33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66–0.75), specificity of 0.79 (95% CI: 0.79–0.80), DOR of 6.92 (95% CI: 4.36–11.00), and AUC of 0.78 (95% CI: 0.72–0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51–0.60), specificity of 0.79 (95% CI: 0.76–0.82), DOR of 6.88 (95% CI: 2.30–20.60), and AUC of 0.77 (95% CI: 0.73–0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52–0.83), specificity of 0.84 (95% CI: 0.68–0.93), DOR of 11.51 (95% CI: 6.14–21.56), and AUC of 0.83 (95% CI: 0.80–0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72–0.85), specificity of 0.89 (95% CI: 0.85–0.93), DOR of 24.64 (95% CI: 6.95–87.37), and AUC of 0.87 (95% CI: 0.81–0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38–0.54), specificity of 0.93 (95% CI: 0.91–0.95), DOR of 19.86 (95% CI: 0.86–456.91), and AUC of 0.86 (95% CI: 0.52–1.00).ConclusionSPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential p...

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Section: Discussionmentioning

confidence: 99%

Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis

et al. 2015

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“…HER2 is currently the only clear therapeutic target for gastric cancer, and the ToGA trial is the first large-scale phase III clinical trial in the world to prove that targeted therapy for gastric cancer can prolong survival, making trastuzumab combined with first-line chemotherapy agents the standard first-line treatment for HER2 -positive advanced gastroesophageal adenocarcinoma[ 76 - 80 ]. However, targeting HER2 has achieved significant efficacy in the treatment of breast cancer, such as trastuzumab combined with paclitaxel or pertuzumab, the combination therapy of lapatinib and the combination therapy of the antibody coupling drug T-DM1, etc.…”

Section: Targeted Therapy For Patients With Her2 G...mentioning

confidence: 99%

Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

Jiang,

Li,

Qiu

et al. 2024

World J Gastrointest Oncol

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Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance. Human epidermal growth factor receptor 2 (HER2 ) is one of the most important targets in targeted therapy for gastric cancer. Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer. The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified. However, monoclonal antibodies, due to their large molecular weight, inability to penetrate the blood-brain barrier, and drug resistance, lead to decreased therapeutic efficacy, so it is necessary to explore the efficacy of other HER2 -targeting therapies in gastric cancer. Small-molecule tyrosine kinase inhibitors, such as lapatinib and pyrrotinib, have the advantages of small molecular weight, penetrating the blood-brain barrier and high oral bioavailability, and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future. Antibo-drug conjugate, such as T-DM1 and T-DXd, can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing, and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab. Therefore, after more detailed stratification of gastric cancer patients, various gastric cancer drugs targeting HER2 are expected to play a more significant role.

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“…Although surgical resection is still often the mainstay of treatment in gastric cancer, increasingly both neoadjuvant and adjuvant therapies are being employed and there is also a growing number of targeted drugs entering the oncology arena [62,63]. It will be important in the future to identify predictive makers of gastric cancer in an era of increasingly tailored therapies and personalised or stratified medicine [64].…”

Section: Predictive Biomarkers In Gastric Cancermentioning

confidence: 99%

Progress in the development of protein biomarkers of oesophageal and gastric cancers

Coghlin

Murray

2016

Proteomics Clinical Apps

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Upper gastrointestinal cancers originating in the oesophagus and stomach often present late and have a very poor prognosis. Treatment options include surgery for localised disease but, increasingly, neoadjuvant chemotherapy and radiotherapy are being employed to improve outcome. There is often a variable response to neoadjuvant treatment between individual patients and side effects are relatively common. There is an urgent need for novel biomarkers of upper gastrointestinal cancer, not only to improve screening and early diagnosis of the oesophageal and gastric cancers when treatment options are potentially more effective, but also to accurately guide therapy in more advanced disease. The development of predictive biomarkers will also help to more effectively identify those patients that will benefit from targeted therapies. Although many promising results have been derived from these studies there remains a lack of validated clinically applicable biomarkers available for translation into routine clinical use. This review will provide an overview of the recent proteomic research on upper gastrointestinal cancer protein biomarker identification and validation. The challenges faced in the development of validated, clinically acceptable and accurate protein biomarkers will also be discussed, along with possible areas of future progress.

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Divide and conquer: subproteomic approaches toward gastric cancer biomarker and drug target discovery

Cited by 5 publications

References 114 publications

Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis

Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis

Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

Progress in the development of protein biomarkers of oesophageal and gastric cancers

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