Identification of lactate metabolism-related subtypes and development of a lactate-related prognostic indicator of lung adenocarcinoma

Abstract

Background: Increasing evidence supports that lactate plays an important role in tumor proliferation, invasion and within the tumor microenvironment (TME). This is particularly relevant in lung adenocarcinoma (LUAD). Therefore, there is a current need to investigate lactate metabolism in LUAD patients and how lactate metabolism is affected by different therapies.Methods: Data from LUAD patients were collected from The Cancer Genome Atlas (TCGA) and patients were divided into two subtypes according to 12 lactate metabolism-related genes to explore the effect of lactate metabolism in LUAD. We established a lactate-related prognostic indicator (LRPI) based on different gene expression profiles. Subsequently, we investigated associations between this LRPI and patient survival, molecular characteristics and response to therapy. Some analyses were conducted using the Genomics of Drug Sensitivity in Cancer (GDSC) database.Results: The two LUAD subtypes exhibited different levels of lactate metabolism, in which patients that displayed high lactate metabolism also had a worse prognosis and a poorer immune environment. Indeed, LRPI was shown to accurately predict the prognosis of LUAD patients. Patients with a high LRPI showed a poor prognosis coupled with high sensitivity to chemotherapy using GDSC data. Meanwhile, these patients exhibited a high responsiveness to immunotherapy in TMB (Tumor mutation burden) and TIDE (Tumor Immune Dysfunction and Exclusion) analyses.Conclusion: We validated the effect of lactate metabolism on the prognosis of LUAD patients and established a promising biomarker. LRPI can predict LUAD patient survival, molecular characteristics and response to therapy, which can aid the individualized treatment of LUAD patients.

Both In Situ and Circulating SLC3A2 Could Be Used as Prognostic Markers for Human Lung Squamous Cell Carcinoma and Lung Adenocarcinoma

“…Primary bronchogenic carcinoma is a malignant tumor that originates from the trachea, bronchus, and lung [ 1 , 2 , 3 ]. Lung cancer is a bronchogenic cancer, examples of which include lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), small-cell carcinoma, and large-cell carcinoma [ 4 , 5 , 6 ]. Lung cancer has a high incidence and mortality worldwide [ 7 ].…”

The mitotic cell cycle‐associated nomogram predicts overall survival in lung adenocarcinoma

“…In addition to relying on the well‐known “Warburg effect” for energy production to support tumor cell growth, 12 tumor cells also use lactic acid to promote their own proliferation and evade immune responses. Elevated levels of lactic acid are strongly associated with tumor metastasis, recurrence, and drug resistance 13,14 . Similarly, tumor cells use glutamine to suppress oxidative stress, maintain mitochondrial membrane integrity, and support the survival of proliferating cells.…”

“…Elevated levels of lactic acid are strongly associated with tumor metastasis, recurrence, and drug resistance. 13 , 14 Similarly, tumor cells use glutamine to suppress oxidative stress, maintain mitochondrial membrane integrity, and support the survival of proliferating cells. Glutamine metabolism also plays a role in enhancing anti‐tumor inflammatory immune responses and participating in the activation of effector T cells.…”