Increased lysyl oxidase‐like 2 associates with a poor prognosis in non‐small cell lung cancer

Zhan, Ping; Lv, Xiaojing; Ji, Yanan; Xie, Hai‐Yan; Yu, Li

doi:10.1111/crj.12584

Cited by 29 publications

(28 citation statements)

References 22 publications

(45 reference statements)

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“…It was found that LOXL2 was significantly overexpressed in NSCLC samples compared to normal tissues; cytoplasmic and nuclear LOXL2 were negligible in healthy lung tissue whereas, in NSCLC specimens, LOXL2 levels were elevated. Furthermore, this increased level of LOXL2 was associated with an increase in tumor size and stage of cancer in adenocarcinoma and squamous cell carcinoma subgroups . This is further supported by silencing of LOXL2, inhibited migration, and invasion in lung squamous cell carcinoma cell lines…”

Section: Is Loxl2 a Viable Cancer Target?mentioning

confidence: 52%

“…Furthermore, this increased level of LOXL2 was associated with an increase in tumor size and stage of cancer in adenocarcinoma and squamous cell carcinoma subgroups. [96] This is further supported by silencing of LOXL2, inhibited migration, and invasion in lung squamous cell carcinoma cell lines. [97] Investigations into the underlying mechanism involved in tumor progression in NSCLC have uncovered endogenous miRNA's (mi-Rs) to be directly involved in LOXL2 expression.…”

Section: Lung Cancermentioning

confidence: 85%

“…LOXL2 m RNA expression in human NSCLC samples were examined and compared to normal lung tissue . It was found that LOXL2 was significantly overexpressed in NSCLC samples compared to normal tissues; cytoplasmic and nuclear LOXL2 were negligible in healthy lung tissue whereas, in NSCLC specimens, LOXL2 levels were elevated.…”

Section: Is Loxl2 a Viable Cancer Target?mentioning

confidence: 99%

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Lysyl Oxidase Like‐2 (LOXL2): An Emerging Oncology Target

Chopra

Sangarappillai

Romero‐Canelón

et al. 2020

Advanced Therapeutics

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Lysyl oxidase‐like 2 (LOXL2) is an emerging drug target against metastatic disease owing to its role in the upregulation of key processes including epithelial‐mesenchymal transition (EMT) and invasion. Recent activity in the field of small molecule LOXL2 inhibitor development by pharmaceutical and academic laboratories has renewed interest in targeting LOXL2. Herein, 1) the viability of LOXL2 as a drug target for the treatment of metastatic disease through an investigation of its biological actions is determined; 2) the pitfalls of an antibody approach are considered; and 3) the small molecule approaches emerging in the scientific and patent literature are reviewed. This review identifies that LOXL2 is localized and active intracellularly and extracellularly in invasive cancer cells. LOXL2 has been implicated in a number of established signaling pathways involved in tumor progression, further highlighting its appeal as a target in metastatic disease. Previously, limited chemical inhibitors have been developed; however, their selectivity profile for the LOX family has proven controversial. Antibodies, such as simtuzumab, have been developed selectively against LOXL2. Simtuzumab, in particular, progresses into phase II trials but it was ultimately terminated. The small molecule inhibitors of LOXL2 are summarized, some of which are now in the early stages of clinical trials.

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Section: Is Loxl2 a Viable Cancer Target?mentioning

confidence: 52%

Section: Lung Cancermentioning

confidence: 85%

Section: Is Loxl2 a Viable Cancer Target?mentioning

confidence: 99%

See 1 more Smart Citation

Lysyl Oxidase Like‐2 (LOXL2): An Emerging Oncology Target

Chopra

Sangarappillai

Romero‐Canelón

et al. 2020

Advanced Therapeutics

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“…The samples were then independently analyzed by two pathologists who did not have any clinical information about the patients. The scores for protein expression were determined as previously described (14,15). Staining intensity was scored as the following: 0 (negative), 1 (weak), 2 (medium) or 3 (strong).…”

Section: Immunohistochemical Staining and Scoring In Tmasmentioning

confidence: 99%

Protein regulator of cytokinesis-1 expression: prognostic value in lung squamous cell carcinoma patients

Zhan

Liu

et al. 2017

J. Thorac. Dis.

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Background: Protein regulator of cytokinesis-1 (PRC1) has been shown to participate in the completion of cytokinesis, and it is dysregulated in cancer processes. However, its relevance in lung squamous cell carcinoma (SCC) remained largely unknown. We aimed to study the expression pattern of PRC1 and assess its clinical significance in lung SCC.Methods: PRC1 protein expression in human lung SCC and adjacent normal lung tissues was detected by immunohistochemistry. PRC1 expression was assessed in association with clinicopathological features and clinical outcomes of lung SCC patients. Results: In lung SCC tissues, PRC1 protein expression was significantly higher than those in paired normal lung tissues. The lung SCC patients with PRC1 overexpression had an advanced pathological stage (TNM stage), positive lymph node metastasis, and a shorter overall survival (OS) time more frequently than patients with low PRC1 expression. Additional, PRC1 expression was also shown to be poor as a prognostic factor for OS in patients with lung SCC. Conclusions: Our study indicated that aberrant expression of PRC1 may point to biochemical recurrence in lung SCC. This highlights its potential as a valuable prognostic marker for lung SCC.

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“…In all the kinds of lung cancers, NSCLC accounts for about 80%, and the 5-year overall survival rate of NSCLC is only 15.9% . Histologically, NSCLC is further comprised of adenocarcinoma (AC) and squamous cell carcinoma (SCC), accounting for approximately 40% and 25%-30% of all lung cancers, respectively (Zhan et al 2016). …”

Section: Introductionmentioning

confidence: 99%

High Serum HDGF Levels Are Predictive of Bone Metastasis and Unfavorable Prognosis in Non-Small Cell Lung Cancer

Zhang

Liu

Chen

et al. 2017

Tohoku J. Exp. Med.

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Hepatoma-derived growth factor (HDGF) is a heparin-binding protein possessing mitogenic activity and could be secreted from necrotic cells passively or actively, thereby functioning as a damage-associated molecular pattern (DAMP). The high expression of HDGF in non-small cell lung cancer (NSCLC) tissues is associated with unfavorable prognosis. However, the clinical significance of serum HDGF has not been elucidated in NSCLC yet. In the present study, we compared the serum levels of HDGF in 235 patients with NSCLC (141 adenocarcinoma and 94 squamous cell carcinoma cases) with those in 40 healthy subjects. Moreover, we explored the correlation between serum HDGF levels and clinicopathologic factors or the overall survival rates. We thus found that the serum HDGF levels were significantly higher in NSCLC patients than those in healthy subjects (P < 0.001). Moreover, there was no significant difference in the serum HDGF levels between adenocarcinoma and squamous cell carcinoma. Importantly, the higher serum levels of HDGF were significantly associated with bone metastasis and with lower overall survival rates. Thus, serum HDGF was identified as an independent prognostic factor indicating poor prognosis of NSCLC. Using A549 human lung adenocarcinoma cell line, we demonstrated that an autophagy inhibitor, chloroquine, could inhibit the HDGF secretion, while quercetin, an autophagy inducer derived from a traditional Chinese drug, could facilitate HDGF secretion. In conclusion, high serum levels of HDGF were significantly correlated to bone metastasis and poorer prognosis of NSCLC. We suggest that anti-HDGF therapy is potential to protect NSCLC patients with advanced stages from bone metastasis.

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Increased lysyl oxidase‐like 2 associates with a poor prognosis in non‐small cell lung cancer

Abstract: These results demonstrate that elevated LOXL2 levels are positively associated with poor prognosis in NSCLC patients. LOXL2 might, therefore, serve as a novel prognostic biomarker and potential therapeutic target in NSCLC patients.

Cited by 29 publications

References 22 publications

Lysyl Oxidase Like‐2 (LOXL2): An Emerging Oncology Target

Lysyl Oxidase Like‐2 (LOXL2): An Emerging Oncology Target

Protein regulator of cytokinesis-1 expression: prognostic value in lung squamous cell carcinoma patients

High Serum HDGF Levels Are Predictive of Bone Metastasis and Unfavorable Prognosis in Non-Small Cell Lung Cancer

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