Overexpression of metabolic markers <scp>PKM</scp>2 and <scp>LDH</scp>5 correlates with aggressive clinicopathological features and adverse patient prognosis in tongue cancer

Yuan, Chunping; Li, Zhongwu; Wang, Yanling; Qi, Bin; Zhang, Wei; Ye, Jinhai; Wu, Heming; Huang, Jiang; Song, Liang‐Nian; Yang, Jianrong; Cheng, Jie

doi:10.1111/his.12441

Cited by 27 publications

(24 citation statements)

References 43 publications

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“…7 Overexpression of PKM2 significantly associated with advanced tumor stages and lymph node metastasis and poor prognosis in diverse cancers including head neck squamous cell carcinoma. 15,16 Our previous findings also revealed essential roles of PKM2 with clinical significance in tongue squamous cell carcinoma, which was the most common subtype of OSCC. Consistently, we extended our previous findings and further measured PKM2 abundance in another independent cohort of primary OSCCs.…”

Section: Discussionmentioning

confidence: 68%

“…16 To further unravel the oncogenic roles of PKM2 during oral carcinogenesis, we developed the hamster buccal pouch carcinogenesis model, which is one of the best characterized animal models for OSCC, and sought to determine the expression pattern of PKM2 during different stages of OSCC carcinogenesis. Upon animal euthanization, gross examinations of hamster buccal pouch revealed no apparent changes in mineral oil-treated control animals, while thickened mucosa with rough surface was observed in 4-week and 10-week DMBA-treated animals.…”

Section: Resultsmentioning

confidence: 99%

“…Consistent with our previous findings and others, our results further indicate that high PKM2 significantly associates with decreased patients' overall and disease-free survival in OSCC. 8,15,16 Its overexpression served as an independent prognostic factor for patients' overall survival. Therefore, PKM2 measurement in OSCC samples might offer valuable clues about patients' prognostic prediction.…”

Section: Discussionmentioning

confidence: 99%

“…16,26 Immunohistochemical staining for PKM2 was performed on 4-mm formalin-fixed, paraffin-embedded tumor specimens. Briefly, tissue sections from representative paraffin blocks were deparaffinised and rehydrated.…”

Section: Histopathological Evaluation and Immunohistochemistrymentioning

confidence: 99%

“…[14][15][16] However, the expression pattern of PKM2 and its clinicopathological significance in OSCC initiation and progression have not been well established thus far. In the present study, we aimed to analyze the PKM2 expression both in an chemical-induced OSCC animal model and primary human specimens and then investigate the relationship between its abundance and clinicopathological features and patients' prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of pyruvate kinase M2 associates with aggressive clinicopathological features and unfavorable prognosis in oral squamous cell carcinoma

Wang¹,

Zhang²,

Zhang

et al. 2015

Cancer Biology & Therapy

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Abnormal glucose metabolism mediated by pyruvate kinase M2 (PKM2) fuels cancer overgrowth and propagation. However, its expression and oncogenic roles in in oral squamous cell carcinoma (OSCC) remains incompletely known. Here, we aimed to investigate the expression of PKM2, its prognostic values and oncogenic functions using 7,12-dimethyl-1,2-bezan-tracene (DMBA)-induced hamster buccal pouch SCC model, primary OSCC specimens as well as in vitro cellular assays. We found that in DMBA-induced OSCC model, negative PKM2 expression was commonly observed in normal epithelial, while more PKM2 abundance was detected in hyperplasia, dysplasia and SCC. Overexpression of PKM2 in a major fraction of OSCC significantly associated with tumor size (P D 0.027), cervical node metastasis (P D 0.004) and clinical stages (P D 0.000). Patients with increased PKM2 had remarkably reduced overall and disease-free survival. Multivariate survival analysis further revealed that PKM served as a critical independent prognostic factor for patients' overall survival. Furthermore, impaired cell proliferation and migration, and reduced apoptosis were detected upon PKM2 knockdown in HN4 and HN12 cells. Taken together, our findings reveal that PKM2 is critically involved in OSCC initiation and progression probably by promoting cell proliferation and migration as well as reducing apoptosis. Its overexpression correlates with aggressive clinicopathological features and poor patients' outcome.

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Section: Discussionmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Histopathological Evaluation and Immunohistochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Overexpression of pyruvate kinase M2 associates with aggressive clinicopathological features and unfavorable prognosis in oral squamous cell carcinoma

Wang¹,

Zhang²,

Zhang

et al. 2015

Cancer Biology & Therapy

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Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma

Zhang

Yuan

et al. 2018

Intl Journal of Cancer

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Despite significant advances in therapy, the 5-year survival rates for patients with advanced stage oral cancers still remains poor as an appropriate treatment has not been found yet, due to side effects of chemo/radiotherapy. Verbascoside (VB), a major bioactive constituent of the Tsoong herb, displays pharmacological properties by exhibiting anti-oxidative, anti-inflammatory and anti-cancer activities. However, the underlining function and mechanism of VB in human oral squamous cell carcinoma (OSCC) remains unclear. In this study, we show that VB significantly decreased the viability and metastasis of HN4 and HN6 tumor cells, while promoting apoptosis. A xenograft OSCC mouse model further showed that intraperitoneal injection of VB strongly inhibited growth and lung metastasis of implanted tumor cells. Immunoblot analysis confirmed that VB effectively suppressed nuclear factor (NF)-κB activation and downstream Bcl-2/Bcl-XL expression, resulting in increased OSCC cell apoptosis. In addition, VB suppressed mRNA and protein expression of matrix metalloproteinase-9 via suppression of NF-κB activation, thereby inhibiting tumor cell metastasis. Inspiringly, compared to cisplatin-treated group, VB is a biocompatible agent without signficant side effects in vivo. Collectively, our results demonstrate that VB effectively inhibits OSCC tumor cell growth and metastasis via suppression of IκB kinase complex (IKK)/NF-κB-related signaling activation, suggesting that VB has potential use as a potent anticancer agent in OSCC therapeutic strategies.

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Prognostic role of glycolysis for cancer outcome: evidence from 86 studies

Chen

Hong

et al. 2019

J Cancer Res Clin Oncol

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Overexpression of metabolic markers PKM2 and LDH5 correlates with aggressive clinicopathological features and adverse patient prognosis in tongue cancer

Abstract: Our data indicate that overexpression of PKM2 and LDH5 associates with key clinicopathological features and unfavourable prognosis in TSCC.

Cited by 27 publications

References 43 publications

Overexpression of pyruvate kinase M2 associates with aggressive clinicopathological features and unfavorable prognosis in oral squamous cell carcinoma

Overexpression of pyruvate kinase M2 associates with aggressive clinicopathological features and unfavorable prognosis in oral squamous cell carcinoma

Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma

Prognostic role of glycolysis for cancer outcome: evidence from 86 studies

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