The prognostic value of autophagy-related markers beclin-1 and microtubule-associated protein light chain 3B in cancers: a systematic review and meta-analysis

He, Yulong; Zhao, Xianda; Subahan, Narishka Roz; Fan, Lifang; Gao, Jun; Chen, Honglei

doi:10.1007/s13277-014-2060-4

Cited by 65 publications

(70 citation statements)

References 46 publications

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“…Several evidences suggest that some proteolytic enzymes, such as calcium-dependent cysteine proteases, are associated with the origin and development of OPIDN [8,14]. Autophagy is an evolutionarily conserved process that can lead to degradation of proteins and entire organelles in eukaryotic cells [15,16]. In response to nutrient-limiting conditions or environmental insults, the autophagy is initiated to form double-membrane autophagosomes.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

et al. 2015

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Organophosphate-induced delayed neuropathy (OPIDN) is pathologically characterized by the swollen axon containing aggregations of microtubules, neurofilaments, smooth endoplasmic reticulum and multivesicular vesicles. At present, the exact mechanism of OPIDN is unclear and the effective therapeutic methods is not available to counter this syndrome. Recent studies had shown that the autophagy was involved in OPIDN. The adipocytokine Apelin is a peptide, Apelin and its receptor are abundantly expressed in the nervous system. Recent researches illuminated that Apelin was neuroprotective factor and Apelin could regulate the autophagy in vivo and vitro model. So we investigated the effect of Apelin-13 on the OPIDN induced by Tri-ortho-cresyl phosphate (TOCP) in hens and explored the role of autophagy in Apelin-13 preventing OPIDN. Adult Roman hens were given a single dose of 750 mg/kg TOCP by gavage for 21 days to induce OPIDN, and neural dysfunction were detected, and the formation of autophagosomes in spinal cord neurons was observed by transmission electron microscopy, and the molecular markers of autophagy microtubule-associated protein light chain-3 (LC3) and the autophagy substrates p62/SQSTM1 were determined by Western blot analysis. The results demonstrated that the obvious neurological dysfunction such as hindlimb paralysis and paralysis of gait was present, the number of autophagosomes in the neurons of spinal cords was significantly increased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly increased in the OPIDN model group compared with the control group. Compared with the OPIDN model group, the neurological dysfunction of tens was obviously reduced, the clinical signs scores was significantly decreased, the number of autophagosomes in the neurons of hen spinal cords was significantly decreased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly decreased in Apelin-13 treatment group. Our results suggested that Apelin-13 prevented against the OPIDN induced by TOCP in hens, which the mechanism might be associated with regulation autophagy flux by Apelin-13.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

et al. 2015

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“…31 A recent meta-analysis confirmed that high expression of LC3B predicts adverse OS in BC. 32 However, none of the aforementioned studies was based on the quantification of LC3B C puncta, and rather scored the overall expression level of LC3B, meaning that the evaluation criteria was rather different from those reported here. We observed that the intensity of LC3B did not correlate with the presence of LC3B C puncta.…”

Section: Discussionmentioning

confidence: 85%

Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer

et al. 2015

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Abbreviations: BC, breast cancer; BCSS, breast cancer-specific survival; CI, confidence interval; HMGB1, high mobility group box 1; HR, hazard ratio; LC3B (MAP1LC3B/LC3B), microtubule-associated protein 1 light chain 3B; MFS, metastasis free survival; OS, overall survival; PBS, phosphate-buffered saline; SQSTM1/p62, sequestosome 1; TLR4, toll-like receptor 4; TMAs, tissue microarrays.In spite of adjuvant chemotherapy, a significant fraction of patients with localized breast cancer (BC) relapse after optimal treatment. We determined the occurrence of cytoplasmic MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3B)-positive puncta, as well as the presence of nuclear HMGB1 (high mobility group box 1) in cancer cells within surgical BC specimens by immunohistochemistry, first in a test cohort (152 patients) and then in a validation cohort of localized BC patients who all received adjuvant anthracycline-based chemotherapy (1646 patients). Cytoplasmic LC3BC puncta inversely correlated with the intensity of SQSTM1 staining, suggesting that a high percentage cells of LC3B C puncta reflects increased autophagic flux. After setting optimal thresholds in the test cohort, cytoplasmic LC3BC puncta and nuclear HMGB1 were scored as positive in 27.2% and 28.6% of the tumors, respectively, in the validation cohort, while 8.7% were considered as double positive. LC3BC puncta or HMGB1 expression alone did not constitute independent prognostic factors for metastasis-free survival (MFS) in multivariate analyses. However, the combined positivity for LC3B C puncta and nuclear HMGB1 constituted an independent prognostic factor significantly associated with prolonged MFS (hazard ratio: 0.49 95% confidence interval [0.26-0.89]; P D 0.02), and improved breast cancer specific survival (hazard ratio: 0.21 95% confidence interval [0.05-0.85]; P D 0.029). Subgroup analyses revealed that within patients with poor-prognosis BC, HMGB1 C LC3B C double-positive tumors had a better prognosis than BC that lacked one or both of these markers. Altogether, these results suggest that the combined positivity for LC3B C puncta and nuclear HMGB1 is a positive predictor for longer BC survival.

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“…5 High expression of the 2 autophagy-relevant proteins ATG5 and RB1CC1/FIP200 has a positive impact on breast cancer patient survival. 6 Although the absolute expression level of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 b) has no major impact on patient survival, 7 the absence of LC3B puncta, which correlates with increased levels of the autophagy receptor SQSTM1/p62 and hence indicates a reduction of autophagic flux, has a negative prognostic impact, as we have reported on 2 cohorts comprising approximately 1700 breast cancer patients who underwent adjuvant chemotherapy. 8 Risk stratification can be further improved when we measure, in addition to LC3B puncta, the nuclear expression of HMGB1.…”

Section: Introductionmentioning

confidence: 91%

The presence of LC3B puncta and HMGB1 expression in malignant cells correlate with the immune infiltrate in breast cancer

et al. 2016

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Several cell-intrinsic alterations have poor prognostic features in human breast cancer, as exemplified by the absence of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 b)-positive puncta in the cytoplasm (which indicates reduced autophagic flux) or the loss of nuclear HMGB1 expression by malignant cells. It is well established that breast cancer is under strong immunosurveillance, as reflected by the fact that scarce infiltration of the malignant lesion by CD8 C cytotoxic T lymphocytes or comparatively dense infiltration by immunosuppressive cell types (such as FOXP3 C regulatory T cells or CD68C tumor-associated macrophages), resulting in low CD8C ratios, has a negative prognostic impact. Here, we reveal the surprising finding that cell-intrinsic features may influence the composition of the immune infiltrate in human breast cancer. Thus, the absence of LC3B puncta is correlated with intratumoral (but not peritumoral) infiltration by fewer CD8C cells and more FOXP3C or CD68 C cells, resulting in a major drop in the CD8 C :FOXP3 C or CD8 C :CD68 C ratios. Moreover, absence of HMGB1 expression in nuclei correlated with a general drop in all immune effectors, in particular FOXP3C and CD68 C cells, both within the tumor and close to it. Combined analysis of LC3B puncta and HMGB1 expression allowed for improved stratification of patients with respect to the characteristics of their immune infiltrate as well as overall and metastasis-free survival. It can be speculated that blocked autophagy in, or HMGB1 loss from, cancer cells may favor tumor progression due to their negative impact on anticancer immunosurveillance.

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The prognostic value of autophagy-related markers beclin-1 and microtubule-associated protein light chain 3B in cancers: a systematic review and meta-analysis

Cited by 65 publications

References 46 publications

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer

The presence of LC3B puncta and HMGB1 expression in malignant cells correlate with the immune infiltrate in breast cancer

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