Serum lactate dehydrogenase is a predictive biomarker in patients with oropharyngeal cancer undergoing radiotherapy: Retrospective study on predictive factors

Uehara, Takuya; Doi, Hiroshi; Ishikawa, Kazuki; Inada, Masahiro; Tatsuno, Saori; Wada, Yutaro; Oguma, Y.; Kawakami, Hisato; Nakamatsu, Kiyoshi; Hosono, Makoto; Nishimura, Yasumasa

doi:10.1002/hed.26814

Cited by 8 publications

(9 citation statements)

References 38 publications

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“… 23 , 24 More limited studies have found LDH to have prognostic significance in head and neck cancers as well. 25 , 26 , 27 , 28 LDH is a key enzyme in anaerobic glycolysis through conversion of pyruvate to lactate and is thought to reflect more aggressive cancers, which are able to proliferate under hypoxic conditions. 25 , 29 Hypoxic tumor conditions are well‐known to lead to resistance to radiation and chemotherapy, indicating that elevated LDH may be an indirect marker of resistance to these treatment modalities.…”

Section: Discussionmentioning

confidence: 99%

“… 25 , 26 , 27 , 28 LDH is a key enzyme in anaerobic glycolysis through conversion of pyruvate to lactate and is thought to reflect more aggressive cancers, which are able to proliferate under hypoxic conditions. 25 , 29 Hypoxic tumor conditions are well‐known to lead to resistance to radiation and chemotherapy, indicating that elevated LDH may be an indirect marker of resistance to these treatment modalities. 30 Our novel findings suggest that elevated serum LDH may also represent resistance to ICIs as well.…”

Section: Discussionmentioning

confidence: 99%

“…Serum LDH has been well‐studied as an important biomarker in certain solid tumors, most notably in non‐Hodgkin's lymphoma and metastatic melanoma, where it is used in staging 23,24 . More limited studies have found LDH to have prognostic significance in head and neck cancers as well 25–28 . LDH is a key enzyme in anaerobic glycolysis through conversion of pyruvate to lactate and is thought to reflect more aggressive cancers, which are able to proliferate under hypoxic conditions 25,29 .…”

Section: Discussionmentioning

confidence: 99%

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Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors

Pan

Voutsinas

et al. 2023

Cancer Medicine

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Background Little is known regarding associations between peripheral blood biomarkers (PBBMs) and survival, response, and toxicity in recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs). Methods In this single‐institution retrospective cohort study, a dataset of patients with R/M HNSCC treated with ICIs between 08/2012–03/2021 was established, including demographic and clinicopathologic characteristics. Pretreatment PBBMs were collected and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv5, objective response (ORR) by RECIST 1.1, overall survival (OS), and progression‐free survival (PFS). Multivariable models for each outcome were created using elastic net variable selection. Results Our study included 186 patients, with 51 (27%) demonstrating complete or partial response to immunotherapy. Multivariable models adjusted for ECOG performance status (PS), p16, and smoking demonstrated that pretreatment higher LDH and absolute neutrophils, as well as lower percent lymphocytes correlated with worse OS and PFS. Higher LDH and lower % lymphocytes also correlated with worse ORR. Conclusions In the largest study to date examining PBBMs in ICI‐treated R/M HNSCCs, our variable selection method revealed PBBMs prognostic for survival and response to immunotherapy. These biomarkers warrant further investigation in a prospective study along with validation with CPS biomarker.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors

Pan

Voutsinas

et al. 2023

Cancer Medicine

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“…For cancer cells that survived in a TME of intermittently hypoxia and starvation, glucose metabolism transforms to glycolysis even in an aerobic environment is ubiquitous ( 5 , 12 ). Metabolites produced by glycolysis support the excessive proliferation and metastasis of cancer cells, such as secreted lactate creates an acidic microenvironment which promoted cancer cells invasion abilities and absconding from chemotherapy ( 13 , 14 ). Therefore, aberrantly elevated glycolysis in cancer cells was thought to be closely related to poor prognosis in malignancies, including ccRCC ( 6 , 15 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Three-Glycolysis-Related lncRNA Signature Correlated With Prognosis and Metastasis in Clear Cell Renal Cell Carcinoma

Tong

Zhu

et al. 2022

Front. Med.

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The clear cell renal cell carcinoma (ccRCC) is not only a malignant disease but also an energy metabolic disease, we aimed to identify a novel prognostic model based on glycolysis-related long non-coding RNA (lncRNAs) and explore its mechanisms. With the use of Pearson correlation analysis between the glycolysis-related differentially expressed genes and lncRNAs from The Cancer Genome Atlas (TCGA) dataset, we identified three glycolysis-related lncRNAs and successfully constructed a prognostic model based on their expression. The diagnostic efficacy and the clinically predictive capacity of the signature were evaluated by univariate and multivariate Cox analyses, Kaplan–Meier survival analysis, and principal component analysis (PCA). The glycolysis-related lncRNA signature was constructed based on the expressions of AC009084.1, AC156455.1, and LINC00342. Patients were grouped into high- or low-risk groups according to risk score demonstrated significant differences in overall survival (OS) period, which were validated by patients with ccRCC from the International Cancer Genome Consortium (ICGC) database. Univariate Cox analyses, multivariate Cox analyses, and constructed nomogram-confirmed risk score based on our signature were independent prognosis predictors. The CIBERSORT algorithms demonstrated significant correlations between three-glycolysis-related lncRNAs and the tumor microenvironment (TME) components. Functional enrichment analysis demonstrated potential pathways and processes correlated with the risk model. Clinical samples validated expression levels of three-glycolysis-related lncRNAs, and LINC00342 demonstrated the most significant aberrant expression. in vitro, the general overexpression of LINC00342 was detected in ccRCC cells. After silencing LINC00342, the aberrant glycolytic levels and migration abilities in 786-O cells were decreased significantly, which might be explained by suppressed Wnt/β-catenin signaling pathway and reversed Epithelial mesenchymal transformation (EMT) process. Collectively, our research identified a novel three-glycolysis-related lncRNA signature as a promising model for generating accurate prognoses for patients with ccRCC, and silencing lncRNA LINC00342 from the signature could partly inhibit the glycolysis level and migration of ccRCC cells.

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“…Previous studies have hypothesized that the metabolic cause of elevated LDH levels in patients with poorer outcomes is related to the presence of increased hypoxia due to the enzyme's function in anaerobic conditions. 34 , 36 …”

Section: Discussionmentioning

confidence: 99%

Age-Dependent Hematologic Toxicity Profiles and Prognostic Serologic Markers in Postoperative Radiochemotherapy Treatment for Uterine Cervical Cancer

Meixner

Hoeltgen

Hoegen

et al. 2022

Technol Cancer Res Treat

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Introduction: In the adjuvant setting for cervical cancer, classical risk factors for postoperative radiochemotherapy have been established. However, data on laboratory changes during therapy and the prognostic value of serological markers are limited and further knowledge is needed to optimize the toxic trimodal regimen. Methods: We retrospectively identified 69 women who underwent weekly postoperative radiochemotherapy with 40 mg/m2 of cisplatin for cervical cancer between 2010 and 2021 at a single center. Laboratory parameters were recorded before, at each cycle and after radiochemotherapy. Kaplan-Meier and log-rank analyses were used to calculate and compare survival, groups were compared using the Mann–Whitney U, χ2, and variance tests. Results: With a median follow-up of 17.7 months, the 1- and 5-year local control rates were 94.0% and 73.7%, respectively, with significantly better rates for more chemotherapy cycles and negative resection margins. Only 68.1% of patients completed all cycles. The most common reasons for early discontinuation were persistent asymptomatic leukopenia in women aged ≤ 50 years, and limiting infections in women aged > 50 years. Leukopenia was more likely to occur after the third cycle. Significantly worse survival was observed for post-radiochemotherapy elevated C-reactive-protein and lactate dehydrogenase levels, low pre-radiochemotherapy nutritional index, and raised C-reactive-protein-levels; the latter were also predictable for local control. The Glasgow prognostic score did not reliably predict survival. Conclusion: Incomplete application of simultaneous chemotherapy leads to inferior local control, and age-dependent limiting factors should be identified at an early stage. In addition to classical risk factors, serological markers (C-reactive-protein, lactate dehydrogenase, nutritional index) show prognostic significance.

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Serum lactate dehydrogenase is a predictive biomarker in patients with oropharyngeal cancer undergoing radiotherapy: Retrospective study on predictive factors

Cited by 8 publications

References 38 publications

Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors

Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors

Identification of a Three-Glycolysis-Related lncRNA Signature Correlated With Prognosis and Metastasis in Clear Cell Renal Cell Carcinoma

Age-Dependent Hematologic Toxicity Profiles and Prognostic Serologic Markers in Postoperative Radiochemotherapy Treatment for Uterine Cervical Cancer

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