Overexpression of α3, β3 and γ2 chains of laminin‑332 is associated with poor prognosis in pancreatic ductal adenocarcinoma

Zhang, Hao; Luo, Jun; Wu, Xiaokang; Li, Xueming; Zhao, Xinyi; Zhou, Dongkai; Yu, Shian

doi:10.3892/ol.2018.8678

Cited by 13 publications

(17 citation statements)

References 33 publications

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“…Furthermore, there was no investigation into the reason that the three LM-332 subunits α3, β3 and γ2, exerted different effects on PDAC cells, nor was there any investigation into the underlying mechanism of this finding, which will form the main focus of future research. In our previous research, enhanced expression of LAMA3, LAMB3 and LAMC2 were confirmed with tissue analysis (17,20). The increased expression levels of the three subunits of LM-332 were significantly associated with worse differentiation, deeper depth of invasion, a more advanced stage and shorter survival time in PDAC.…”

Section: Discussionmentioning

confidence: 55%

“…It was recently demonstrated that upregulation of LAMA3 is associated with poor prognosis in PDAC (17). In our previous study, the increased expression of LAMA3 was significantly associated with worse differentiation, deeper depth of invasion, more advanced stage, and shorter survival time in PDAC (17). In addition, LAMA3 expression was assessed in human PDAC cells and it was revealed that it was significantly higher in PANC1 cells than in H6C7 cells.…”

Section: Discussionmentioning

confidence: 89%

“…The α3 chain of LM-332 is essential for the interaction with α3β1 integrin, which promotes cell adhesion, migration and invasion (28). It was recently demonstrated that upregulation of LAMA3 is associated with poor prognosis in PDAC (17). In our previous study, the increased expression of LAMA3 was significantly associated with worse differentiation, deeper depth of invasion, more advanced stage, and shorter survival time in PDAC (17).…”

Section: Discussionmentioning

confidence: 93%

“…It has been reported that the cytoplasmic expression of LAMC2 demonstrates high invasive potential of tumors and is correlated with distant metastasis, particularly hepatic metastasis, and poor prognosis (27). Similarly, it has recently been demonstrated that overexpression of LAMC2 is associated with poor prognosis in PDAC (17). However, the presence of γ2 appears to predict an improved prognosis in breast and colon cancer (35,36).…”

Section: Discussionmentioning

confidence: 96%

“…All qPCR analyses were performed in triplicate. Results were calculated using the 2 -ΔΔCq method (17).…”

Section: Reverse Transcription-quantitative Pcr (Rt-qpcr)mentioning

confidence: 99%

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Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Huang

2020

Mol Med Rep

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The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is primarily due to the invasive and metastatic behaviors of this disease. Laminin-332 (LM-332) is a key component of the basement membrane barrier, and is associated with tumor metastasis. The present study provides evidence towards the potential function of LM-332 in carcinoma, indicating the distinct roles of the three LM-332 subunits (α3, β3 and γ2) in cell proliferation, migration, invasion, apoptosis and the epithelial-to-mesenchymal transition (EMT) in cancer. The roles of the α3, β3 and γ2 subunits in the malignant biological behavior of PDAC were investigated in the present study. It was revealed that the α3, β3 and γ2 subunits were upregulated in PDAC. Inhibition of all LM-332 subunits abrogated the tumorigenic outcomes, which included cell proliferation, apoptosis, invasion, migration and EMT in vitro. However, the three LM-332 subunits had different degrees of effects on biological behavior. It was observed that LAMA3 (α3) had a stronger effect on cell proliferation, migration and invasion. In addition, LAMB3 (β3) knockdown significantly increased E-cadherin levels and decreased vimentin levels, indicating that LAMB3 was associated with EMT. Likewise, LAMC2 (γ2) mediated proliferation, apoptosis, invasion and migration. However, small interfering (si)-LAMC2 promoted the progression of EMT, which was the opposite effect to that of si-LAMB3. The LM-332 subunits (α3, β3 and γ2) may be novel therapeutic targets of PDAC in the future.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 96%

“…All qPCR analyses were performed in triplicate. Results were calculated using the 2 -ΔΔCq method (17).…”

Section: Reverse Transcription-quantitative Pcr (Rt-qpcr)mentioning

confidence: 99%

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Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Huang

2020

Mol Med Rep

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Cell-binding peptides on the material surface guide stem cell fate of adhesion, proliferation and differentiation

et al. 2023

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Validation of the novel GLAS algorithm as an aid in the detection of liver fibrosis and cirrhosis based on GP73, LG2m, age, and sex

Hemken,

Qin,

Sokoll

et al. 2023

Clin Proteom

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Background Diagnosis of liver disease at earlier stages can improve outcomes and reduce the risk of progression to malignancy. Liver biopsy is the gold standard for diagnosis of liver disease, but is invasive and sample acquisition errors are common. Serum biomarkers for liver function and fibrosis, combined with patient factors, may allow for noninvasive detection of liver disease. In this pilot study, we tested and validated the performance of an algorithm that combines GP73 and LG2m serum biomarkers with age and sex (GLAS) to differentiate between patients with liver disease and healthy individuals in two independent cohorts. Methods To develop the algorithm, prototype immunoassays were used to measure GP73 and LG2m in residual serum samples collected between 2003 and 2016 from patients with staged fibrosis and cirrhosis of viral or non-viral etiology (n = 260) and healthy subjects (n = 133). The performance of five predictive models using combinations of age, sex, GP73, and/or LG2m from the development cohort were tested. Residual samples from a separate cohort with liver disease (fibrosis, cirrhosis, or chronic liver disease; n = 395) and healthy subjects (n = 106) were used to validate the best performing model. Results GP73 and LG2m concentrations were higher in patients with liver disease than healthy controls and higher in those with cirrhosis than fibrosis in both the development and validation cohorts. The best performing model included both GP73 and LG2m plus age and sex (GLAS algorithm), which had an AUC of 0.92 (95% CI: 0.90–0.95), a sensitivity of 88.8%, and a specificity of 75.9%. In the validation cohort, the GLAS algorithm had an estimated an AUC of 0.93 (95% CI: 0.90–0.95), a sensitivity of 91.1%, and a specificity of 80.2%. In both cohorts, the GLAS algorithm had high predictive probability for distinguishing between patients with liver disease versus healthy controls. Conclusions GP73 and LG2m serum biomarkers, when combined with age and sex (GLAS algorithm), showed high sensitivity and specificity for detection of liver disease in two independent cohorts. The GLAS algorithm will need to be validated and refined in larger cohorts and tested in longitudinal studies for differentiating between stable versus advancing liver disease over time.

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Overexpression of α3, β3 and γ2 chains of laminin‑332 is associated with poor prognosis in pancreatic ductal adenocarcinoma

Cited by 13 publications

References 33 publications

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Cell-binding peptides on the material surface guide stem cell fate of adhesion, proliferation and differentiation

Validation of the novel GLAS algorithm as an aid in the detection of liver fibrosis and cirrhosis based on GP73, LG2m, age, and sex

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