LAMC2 as a prognostic biomarker in human cancer: a systematic review and meta-analysis

Our plain-English summary of LAMC2 as a prognostic biomarker in human cancer: a systematic review and meta-analysis, by T. Fu, J.X. Liu, J. Xie, et al (BMJ Open, 2022).

The study

• Authors: T. Fu, J.X. Liu, J. Xie, Z. Gao, Z. Yang
• Journal: BMJ Open
• Published: 2022;12(11):e063682
• Type of article: Meta-analysis, Systematic review
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Accumulating evidence suggested that the laminin γ2 (LAMC2) expression level was upregulated in various cancers. However, the potential prognostic value of LAMC2 in cancers remains unclear. We conducted a meta-analysis to clarify the association of LAMC2 expression with prognosis.

Design: We searched Embase, Web of Science and PubMed (up to 25 November 2021) to collect all eligible studies, and meta-analysis was performed to interpret the association of LAMC2 expression with clinicopathological parameters, overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS).

Eligibility Criteria For Including Studies: We included studies that investigate the relationship between LAMC2 and prognosis of cancers, patients were divided into two groups, and associations of LAMC2 expression with clinicopathological features were described.

Results: Seven studies were finally included. We found that increased LAMC2 expression was significantly associated with lymph node metastasis (log OR 0.88, 95% CI 0.38 to 1.38, p<0.001), tumour-node-metastasis stages (log OR: 0.95, 95% CI 0.39 to 1.50, p<0.001) and tumour status (log OR 1.26, 95% CI 0.84 to 1.68, p<0.001), but not with age (log OR -0.05, 95% CI -0.37 to 0.27, p=0.75) or gender (log OR -0.07, 95% CI -0.52 to 0.38, p=0.75). In addition, higher LAMC2 expression was found to be significantly associated with OS/PFS/DSS (HR 1.85, 95% CI 1.31 to 2.40, p<0.001). A similar result was found in The Cancer Genome Atlas database. High LAMC2 expression was significantly associated with OS in lung adenocarcinoma, mesothelioma, skin cutaneous melanoma, neck squamous cell carcinoma and brain lower grade glioma.

Conclusion: Our results suggested that higher LAMC2 expression was correlated with worse survival, lymph node metastasis, tumour-node-metastasis stages and tumour status. This study was subject to inherent limitations, but the results presented here provide insights regarding the potential use of LAMC2 as a biomarker for human cancer.

Study Registration: researchregistry.com (researchregistry1319).

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This article was a systematic review and meta-analysis, not a study of asbestos. The authors searched Embase, Web of Science and PubMed up to 25 November 2021 for studies linking expression of LAMC2 (laminin γ2) to cancer outcomes. They pooled 7 studies with 1056 patients covering six cancer types, none of them mesothelioma. Five studies were from China and two from Japan. Higher LAMC2 was significantly associated with lymph node metastasis, TNM stage and tumour status, but not with age or gender. In 5 studies with 872 patients, higher LAMC2 was associated with worse combined overall, progression-free or disease-specific survival (HR 1.85, 95% CI 1.31 to 2.40). Using The Cancer Genome Atlas database, the authors reported that LAMC2 was significantly associated with overall survival in several cancers, including mesothelioma, but not in lung squamous cell carcinoma. The text gives no mesothelioma numbers. The authors concluded LAMC2 might be a valuable prognostic biomarker, noting the few studies and possible limitation to Asian populations.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: systematic review and meta-analysis of published studies, with an additional analysis of The Cancer Genome Atlas (TCGA) data using the GEPIA web tool
• Who was studied: 7 published studies (2017 to 2021) with 1056 patients with cancer: oesophageal squamous cell carcinoma (1), pancreatic ductal adenocarcinoma (2), cholangiocarcinoma (1), papillary thyroid cancer (1), colorectal cancer (1) and penile squamous cell carcinoma (1). Five studies were from China and two from Japan. The TCGA analysis included 9502 patients.
• Exposure: Not an asbestos exposure. The factor studied was high versus low expression of LAMC2 (laminin γ2) in patients' cancers. The included studies measured it by qRT-PCR, RNA sequencing or immunohistochemistry. No asbestos or fiber exposure was studied.
• Main results:
  • Pooled across included studies, high LAMC2 expression was significantly associated with lymph node metastasis (log OR 0.88, 95% CI 0.38 to 1.38, p less than 0.001).
  • High LAMC2 expression was significantly associated with TNM stage (log OR 0.95, 95% CI 0.39 to 1.50, p less than 0.001).
  • In four studies, high LAMC2 expression was significantly associated with tumour status (log OR 1.26, 95% CI 0.84 to 1.68, p less than 0.001).
  • There was no significant association with age (log OR minus 0.05, 95% CI minus 0.37 to 0.27, p=0.75) or gender (log OR minus 0.07, 95% CI minus 0.52 to 0.38, p=0.75).
  • In 5 studies with 872 patients, higher LAMC2 expression was associated with worse combined overall, progression-free or disease-specific survival (HR 1.85, 95% CI 1.31 to 2.40, p less than 0.001).
  • The authors found no obvious publication bias (Begg's test p=0.4624; Egger's test p=0.329).
  • In the TCGA data for 9502 patients, higher LAMC2 expression was associated with poor overall survival.
  • In TCGA data by cancer type, LAMC2 expression was significantly associated with overall survival in lung adenocarcinoma, mesothelioma, skin cutaneous melanoma, head and neck squamous cell carcinoma and brain lower grade glioma, but not in lung squamous cell carcinoma. The text gives no numbers.
• The authors' conclusion: The authors concluded that LAMC2 might be a valuable biomarker for predicting prognosis in patients with cancer, and that more high-quality, larger studies are needed.
• Limitations the authors state:
  • Only seven studies were included, which might affect the reliability of the results.
  • All included studies were from China or Japan, so the results may apply only to Asian populations.
  • There was no agreed cut-off for what counts as high LAMC2 expression.
  • Some studies did not report hazard ratios, so the authors estimated them from survival curves, with possible errors.
  • The limited numbers of patients and tumour types mean the results may exaggerate the prognostic value of LAMC2.
  • Grey literature was not searched.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Systematic Review, Meta-Analysis, Prognosis, Overall Survival, Progression-Free Survival, Metastasis, Lung Adenocarcinoma.

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