Mutations of key driver genes in gastric cancer metastasis risk: a systematic review and meta-analysis

ABSTRACT

Objective: Associations between gene mutations and metastasis in gastric cancer (GC) remain contradictory, resulting in the inaccurate estimation of the magnitude of the risk associated with specific genotypes.

Methods: In this study, we first screened out four key driver genes (TP53, PIK3CA, APC and ARID1A) by jointly analyzing the mutation levels and searching the literature for genes associated with GC metastasis. We then performed a meta-analysis to demonstrate the relationship between these key driver gene mutations and GC metastasis, including lymphatic and distance metastasis.

Results: We found out four key driver genes (TP53, PIK3CA, APC and ARID1A), associated with risk of GC metastasis. The results showed that TP53 (OR 1.39, 95% CI 1.12–1.72) and APC mutations (OR 0.58, 95% CI 0.38–0.89) were associated with lymph node metastasis and distant metastasis in GC. And TP53 mutations (OR 1.65, 95% CI 1.25–2.18) were significantly related to GC metastasis in the Asian population. APC mutations (OR 0.54, 95% CI 0.29–1.00) were also related to GC metastasis in the European and American populations. There was no significant association with GC metastasis in PIK3CA or ARID1A mutations.

Expert opinion:Mutations of TP53 and APC play important roles in lymph node metastasis and distant metastasis of GC and may be potential important biomarkers of progression and therapeutic targets. These observations should be further prospectively verified.

KEYWORDS:

• Mutation
• gastric cancer
• metastasis
• meta-analysis
• TP53

Acknowledgments

The authors would like to acknowledge the Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education (China Medical University, Shenyang, China) for providing the space and equipment for conducting the experiments.

Disclosure of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability statement

All data generated or analyzed in this study are included in this published article.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work is supported by the National Natural Science Foundation of China [No.81902998], Construction Program of Clinical Cooperation Ability of Chinese and Western Medicine for Major and Difficult Diseases [No. 2018-3], Cooperation Ability of Chinese and Western Medicine for Major and Difficult Diseases [No. 2019-163], The General Projects of Liaoning Province Colleges and Universities [LFWK201706], Science and Technology Youth Projects of the Education Department of Liaoning Province [QN2019004].