Abstract
Objective At present, the relationship between autophagosomes and the prognosis of various cancers has become a subject of active investigation. A series of studies have demonstrated the correlation between autophagy microtubule-associated protein light chain 3 (LC-3), Beclin-1, and colorectal cancer (CRC). Since autophagy has dual regulatory roles in tumors, the results of this correlation are also uncertain. Hence, we summarized the relationship between Beclin-1, LC-3, and CRC using systematic reviews and meta-analysis to clarify their prognostic significance in it. Methods PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched online up to April 1, 2019. The quality of the involving studies was assessed against the Newcastle-Ottawa Scale (NOS). Pooled hazard ratio (HR) and 95% confidence interval (CI) in a fixed or random effects model were used to assess the strength of correlation between Beclin-1, LC-3, and CRC. Results A total of 9 articles were collected, involving 2,297 patients. Most literatures scored more than 6 points, suggesting that the quality of our including research was acceptable. Our finding suggested that the expression of Beclin-1 was not associated with overall survival (HR = 0.68, 95% CI (0.31–1.52), P=0.351). Nonetheless, LC-3 expression exerted significant impact on OS (HR = 0.51, 95% CI (0.35–0.74), P < 0.05). Subgroup analysis exhibited that Beclin-1 expression was associated with OS at TNM stage III (HR = 0.04, 95% CI = 0.02–0.08, P < 0.05), surgical treatment (HR = 1.53, 95% CI (1.15–2.02), P=0.003), and comprehensive treatment (HR = 0.27 95% CI (0.08–0.92), P=0.036), respectively. Similarly, the results showed the increased LC-3 expression in CRC was related to OS in multivariate analyses (HR = 0.44, 95% CI (0.34–0.57), P < 0.05), stages (HR = 0.51, 95% CI (0.35–0.74), P < 0.05), and comprehensive treatment (HR = 0.44, 95% CI (0.34–0.57), P < 0.05). Conclusions Autophagy-related proteins of LC-3 might be an important marker of CRC progression. However, since the number of the original studies was limited, more well-designed, large-scale, high-quality studies are warranted to provide more convincing and reliable information.
Highlights
Colorectal cancer (CRC), with its mortality rate occupying the third place, represents the third most common malignancy in men and women worldwide [1]
The title and abstract of relevant articles were read by two authors (Jinxiao Li and Qian Yan) independently, and 444 citations were excluded after the first screening, with 26 included for fulltext review
We found that Beclin-1 overexpression was associated with reduced survival in the surgically-treated CRC patients, while in the patients treated with comprehensive treatment, elevated Beclin-1 levels was associated with prolonged overall survival (OS)
Summary
Colorectal cancer (CRC), with its mortality rate occupying the third place, represents the third most common malignancy in men and women worldwide [1]. It is estimated that by 2030, the number of newly diagnosed cases and cancer-related deaths of CRC will reach more than 2.2 million and 1.1 million, respectively. The global burden is expected to increase by 60% [2]. Despite the substantial development in the diagnosis and treatment of CRC, such as surgery and neoadjuvant and palliative care, the 5-year overall survival (OS) rate for CRC reportedly was still as low as 23.2% and the 5-year cumulative mortality rate stood at 71.3% [3, 4]. It is necessary to look for an effective biomarker to predict the prognosis of CRC.
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