High expressions of LDHA and AMPK as prognostic biomarkers for breast cancer

Huang, Xiaojia; Li, Xing; Xie, Xinhua; Ye, Feng; Chen, Bin; Song, Cailu; Tang, Hailin

doi:10.1016/j.breast.2016.08.014

Cited by 107 publications

(74 citation statements)

References 37 publications

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“…Lactate dehydrogenase A (LDHA) catalyzes the step of aerobic glycolysis converting pyruvate to lactate in the cytoplasm. Compared to luminal breast cancer cells, TNBC cells exhibit higher LDHA levels and lower oxygen consumption rates (51). MiR-34a dampens the function of both programmed cell death receptor ligand 1 (PDL1) and LDHA.…”

Section: Glycolysismentioning

confidence: 99%

Metabolic Reprogramming in Triple-Negative Breast Cancer

et al. 2020

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Metabolic reprogramming is an emerging hallmark of cancer cells, in which cancer cells exhibit distinct metabolic phenotypes to fuel their proliferation and progression. The significant advancements made in the area of metabolic reprogramming make possible new strategies for overcoming malignant cancer, including triple-negative breast cancer. Triple-negative breast cancer (TNBC) is associated with high histologic grade, aggressive phenotype, and poor prognosis. Even though triple-negative breast cancer patients benefit from standard chemotherapy, they still face high recurrence rates and are more likely to develop resistance to chemotherapeutic drugs. Therefore, there is an urgent need to explore vulnerabilities of triple-negative breast cancer and develop novel therapeutic drugs to improve clinical outcomes for triple-negative breast cancer patients. Metabolic reprogramming may provide promising therapeutic targets for the treatment of triple-negative breast cancer. In this paper, we primarily discuss how triple-negative breast cancer cells reprogram their metabolic phenotype and that of stromal cells in the microenvironment to survive under nutrient-poor conditions. Considering that metastasis and chemoresistance are the main contributors to mortality in triple-negative breast cancer patients, we also focus on the role of metabolic adaption in mediating metastasis and chemoresistance of triple-negative breast cancer tumors.

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Section: Glycolysismentioning

confidence: 99%

Metabolic Reprogramming in Triple-Negative Breast Cancer

et al. 2020

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“…Breast cancer, a highly heterogeneous disease, is one of the most commonly diagnosed types of cancer and the second most common cause of cancer-associated mortality in women globally ( 1 , 2 ). Breast cancer metastasizes to the distant organs and an increased number of patients with breast cancer with earlier stages survive their disease for at least 5 years compared with patients diagnosed with cancer metastasis ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

miR-96 promotes breast cancer metastasis by suppressing MTSS1

2018

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Novel, non-invasive biomarkers with high sensitivity and specificity are critical for breast cancer treatment, and prognosis. MicroRNA (miR)-96 has been demonstrated to be highly expressed in several solid malignancies, including breast cancer. However, its expression and function in the metastasis and prognosis of breast cancer have not been fully explored, and its regulation mechanisms remain unclear. In the present study, the serum miR-96 expression in healthy controls, benign and malignant breast cancer types was compared by using reverse transcription-quantitative polymerase chain reaction. The effect of chemotherapy on miR-96 expression in breast cancer was also investigated. Result revealed that miR-96 expression was increased in malignant breast cancer types and reduced in patients following chemotherapy treatment. The effect of miR-96 manipulation on the migration of breast cancer cells was also investigated by using wound healing, and Transwell migration assays. These results revealed that the induced expression of miR96 led to enhanced wound closing and trans-membrane cell numbers. By using bioinformatics analysis, western blotting and immunohistochemical staining, the metastasis suppressor-1 (MTSS1) gene was identified to be the functional target of miR-96 in the promotion of cell migration. In conclusion, it was identified that miR-96 exhibited an increased level in serum samples of patients with malignant breast cancer in comparison with benign breast tumor types and health controls and may be substantially reduced by chemotherapy treatment, implying that it may be used as a prognostic marker in breast cancer. miR-96 overexpression may inhibit migration of breast cancer cells by downregulating MTSS1 expression.

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“…However, whether that meant that HK2, PKM2 and LDHA were not prognostic factors for mCRC treated with cetuximab remained unknown. Many studies have reported that high expression of HK2 was associated with poor survival outcomes in some tumor types, such as breast cancer ( 21 ), gastric cancer ( 15 ), non-small-cell lung cancer ( 22 ), non-Hodgkin lymphoma ( 23 ), nasopharyngeal carcinoma ( 13 ), hepatocellular carcinoma ( 17 ), cervical squamous cell carcinoma ( 24 ), and pancreatic cancer ( 25 ), among others. A meta-analysis revealed that HK2 overexpression was significantly associated with a worse OS and PFS in solid tumors ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of HK2, PKM2 and LDHA on Cetuximab efficacy in metastatic colorectal cancer

et al. 2018

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Although hexokinase (HK) 2, pyruvate kinase muscle (PKM) isozyme 2 and lactate dehydrogenase (LDH) A predict the efficacy of medicines in various solid tumors, their ability to predict the efficacy of cetuximab in metastatic colorectal cancer (mCRC) remains unclear. mCRC patients with pathological specimens who received cetuximab and chemotherapy from 2005 to 2015 in the present institution were enrolled. Immunohistochemistry was used to detect HK2, PKM2 and LDHA expression. SPSS20 was used for statistical analysis. A total of 68 patients were included; 33 received cetuximab plus chemotherapy as first-line therapy, and the rest, as second- or later-line therapy. HK2 expression levels were increased in cancer compared with normal tissue (75.4% vs. 40%; P<0.001), however PKM2 (P=0.243) and LDHA (P=0.067) expression levels were not. For progression-free survival (PFS) with first-line cetuximab plus chemotherapy, patients with high HK2 expression exhibited longer PFS compared with those with low HK2 expression (23.9 months vs. 6.9 months; P=0.021). However, this positive association was absent in 35 cases administered first-line chemotherapy alone (13.4 months vs. 13.5 months; P=0.539). LDHA expression was associated with the PFS of patients receiving first-line chemotherapy (18.3 and 10.1 months for high and low expression, respectively; P=0.005), whereas this association was absent in cetuximab plus chemotherapy cases (19.9 months vs. 12 months; P=0.522). Furthermore, high LDHA expression correlated with high overall response rate (ORR) (72.2% vs. 15.4%, P=0.006) for chemotherapy, however not disease control rate (DCR) (P=0.074). Neither DCR nor ORR were associated with HK2 expression. PKM2 expression did not affect PFS, DCR or ORR. LDHA expression (P=0.005), pathological differentiation (P=0.019) and synchronous/metachronous metastasis (P=0.014) were independent predictive factors of PFS for all first-line patients, and tumor differentiation (P=0.002) was associated with overall survival (OS) in multivariate analysis. HK2, PKM2 and LDHA did not impact OS. It was concluded that HK2 expression was increased in colorectal cancer tissue and may predict cetuximab efficacy and LDHA for chemotherapy treatment of mCRC.

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High expressions of LDHA and AMPK as prognostic biomarkers for breast cancer

Cited by 107 publications

References 37 publications

Metabolic Reprogramming in Triple-Negative Breast Cancer

Metabolic Reprogramming in Triple-Negative Breast Cancer

miR-96 promotes breast cancer metastasis by suppressing MTSS1

Effect of HK2, PKM2 and LDHA on Cetuximab efficacy in metastatic colorectal cancer

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