Prognostic significance of LAT1 expression in pleural mesothelioma

Our plain-English summary of Prognostic significance of LAT1 expression in pleural mesothelioma, by R. Taguchi, K. Kaira, Y. Miura, et al (Heliyon, 2024).

The study

• Authors: R. Taguchi, K. Kaira, Y. Miura, T. Umesaki, A. Mouri, H. Imai, H. Kagamu, M. Yasuda, Y. Kanai, H. Nitanda, H. Ishida, H. Sakaguchi
• Journal: Heliyon
• Published: 2024;10(17):e37414
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The L-type amino acid transporter (LAT1) exhibits significantly increased expression within tumor cells across various neoplasms. However, the clinical significance of LAT1 expression in patients with pleural mesothelioma (PM) remains unclear.

Methods: Eighty patients diagnosed with PM between June 2007 and August 2022, were eligible for this study. LAT1, alanine-serine-cysteine transporter 2 (ASCT2), Ki-67, and VEGFR2 were evaluated by immunohistochemistry. Inflammatory and nutritional indices were also correlated with different variables, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and Glasgow prognostic score (GPS).

Results: LAT1 was highly expressed in 57.5 % of patients with PM. Among the 80 patients included in this study, 65 (81.3 %) received chemotherapy, either alone or followed by surgical resection, while 15 (18.7 %) opted for best supportive care. The level of LAT1 significantly correlated with cell proliferation and ASCT2. Factors such as performance status, histology, LAT1 expression, PNI, ALI, and GPS were significant prognostic indicators for progression-free survival (PFS), while Ki-67, LAT1, NLR, SII, PNI, ALI, and GPS were identified as significant predictors for overall survival (OS). LAT1 expression emerged as an independent prognostic factor for predicting PFS and OS in all patients, as well as in the subgroup of 65 patients receiving chemotherapy. Notably, high LAT1 expression proved to be a significant predictor of outcome, particularly in the subgroup with high PLR and SII.

Conclusion: LAT1 was a significant predictor of outcomes in patients with PM and was more predictive of worse outcomes in patients with high inflammatory and low nutritional status.

© 2024 The Authors.

In plain English

This retrospective study from one hospital in Japan examined tumor samples from 80 patients diagnosed with pleural mesothelioma between June 2007 and August 2022. The authors measured LAT1, a protein that carries amino acids into cells, and compared it with other markers, blood measures of inflammation and nutrition, and survival. Thirty-three patients had a recorded asbestos history. LAT1 levels did not differ significantly by asbestos history, and asbestos history was not a statistically significant predictor of survival. High LAT1 was found in 46 of 80 patients (57.5 %). These patients had shorter median progression-free survival (181 vs 377 days) and overall survival (476 vs 1029 days). After adjustment, in all 80 patients, high LAT1 predicted worse progression-free survival (hazard ratio 1.696, 95 % CI 1.031 to 2.785) and overall survival (2.973, 95 % CI 1.466 to 6.029). In the 65 systemically treated patients, the ratios were 1.738 (1.005 to 3.006) and 3.362 (1.505 to 7.512). The authors concluded LAT1 predicted worse outcomes, especially with high inflammation and poor nutrition. They noted varied treatments may have biased results, and LAT1's value for individual regimens remains unclear.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective single-institution clinicopathological study using immunohistochemistry on tumor specimens and survival analysis
• Who was studied: Of 85 patients histologically confirmed to have pleural mesothelioma at the authors' institution in Japan between June 2007 and August 2022, 80 had sufficient tumor specimens and were enrolled. Of these, 20 received systemic treatment followed by surgery, 45 received systemic treatment without surgery, and 15 received best supportive care.
• Exposure: The main factor studied was LAT1 expression in tumor tissue, measured by immunohistochemistry. Asbestos exposure history was recorded as a patient characteristic: 33 of 80 patients had it and 47 did not. The proportion with asbestos history did not differ significantly between the high-LAT1 group (19/27) and the low-LAT1 group (14/20) (p = 0.991).
• Main results:
  • High LAT1 expression was found in 57.5 % (46/80) of the patients' tumors.
  • In all 80 patients, LAT1 level correlated with Ki-67, a marker of cell growth (Spearman 0.258, 95 % CI 0.034–0.457, p = 0.021). It also correlated with the transporter ASCT2 (0.227, 95 % CI 0.001–0.431, p = 0.043). It did not correlate with the other markers tested.
  • Across all 80 patients, median progression-free survival was 237 days and median overall survival was 603 days.
  • In all 80 patients, high LAT1 was an independent predictor in multivariate analysis. For progression-free survival: HR 1.696, 95 % CI 1.031-2.785, p = 0.037 (median 181 vs 377 days, high vs low LAT1). For overall survival: HR 2.973, 95 % CI 1.466-6.029, p = 0.003 (median 476 vs 1029 days).
  • In the 65 patients who received systemic treatment with or without surgery, multivariate analysis found LAT1 to be an independent predictor of poor progression-free survival (HR 1.738, 95 % CI 1.005-3.006, p = 0.048). It also predicted poor overall survival (HR 3.362, 95 % CI 1.505-7.512, p = 0.003).
  • In all patients, high LAT1 predicted worse progression-free survival in several subgroups: stage III or IV disease, high PLR, high SII, low PNI, and high GPS. For example, in the high-PLR subgroup median PFS was 155 vs 403 days (p = 0.0002). High LAT1 also predicted poor overall survival in subgroups with stage III or IV disease, epithelial type, high PLR, high SII, and low ALI.
  • In all 80 patients, asbestos history (yes vs no) was not a statistically significant factor for progression-free survival in univariate analysis (median 285 vs 208 days, p = 0.773).
  • In all 80 patients, asbestos history (yes vs no) was not a statistically significant factor for overall survival in univariate analysis (median 564 vs 986 days, p = 0.242).
• The authors' conclusion: The authors concluded that LAT1 was highly expressed in pleural mesothelioma and was an independent predictor of worse outcomes following any treatment. They also concluded it was more predictive of worse outcomes in high-inflammatory and low-nutritional settings.
• Limitations the authors state:
  • The therapeutic strategies were varied (chemotherapy followed by surgery, chemotherapy alone, immunotherapy, or best supportive care), which the authors said may have introduced bias into the results.
  • Patients received varied treatments because patients were enrolled over a long period.
  • How useful LAT1 is as a predictor for individual treatment regimens remains unclear.
  • The cut-off values (medians) used for Ki-67, CD8, FOXP3 and ASCT2 may introduce bias because the study population was limited.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Neoplasm, Ki-67, Immunohistochemistry, Inflammation, Lung Cancer, Chemotherapy, Surgical Resection.

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