Identification of a prognostic index system and tumor immune infiltration characterization for lung adenocarcinoma based on mRNA molecular of pyroptosis.

Background And Purpose: Pyroptosis is a form of programmed cell death, which plays an important role in tumorigenesis, progression, and regulation of the tumor microenvironment. It can affect lung adenocarcinoma (LUAD) progression. This study aimed to construct a pyroptosis-related mRNA prognostic index (PRMPI) for LUAD and clarify the tumor microenvironment infiltration characterization of LUAD.

Materials And Methods: We performed a univariate Cox regression analysis for pyroptosis-related mRNAs in the TCGA cohort. Then, we used LASSO Cox regression to establish a PRMPI. The quantitative real time polymerase chain reaction (qRT-PCR) was used to quantify the relative expression of pyroptosis-related mRNAs. The CPTAC cohort was used to confirm the stability and wide applicability of the PRMPI. The single-sample gene set enrichment analysis (ssGSEA) was performed to assess the tumor microenvironment infiltration characterization.

Results: A total of 36 pyroptosis-related mRNAs were identified. The PRMPI was established based on five pyroptosis-related mRNAs. The expression patterns of these mRNAs were verified in LUAD samples from our medical center by qRT-PCR. High-PRMPI patients had worse overall survival than low-PRMPI patients. The result was validated in the CPTAC cohort. The comprehensive analysis indicated that the high-PRMPI patients exhibited lower immune activity, more aggressive immunophenotype, lower expression of immune checkpoint molecule, higher TP53 mutation rate, and higher tumor stemness than low-PRMPI patients. Low-PRMPI patients may be more sensitive to immunotherapy, while high-PRMPI patients may benefit more from chemotherapy and targeted therapy.

Conclusions: The PRMPI may be a promising biomarker to predict the prognosis, tumor microenvironment infiltration characterization, and the response to adjuvant therapy in LUAD.