Cancer Research and Treatment

Original Articles

Lipid Metabolism Related Gene ACSL3 as a Biomarker for Predicting Immunotherapy Outcomes in Lung Adenocarcinoma: Taiping He, Jinhan Hu, Haoyue Guo, Meng Diao, Yuanyuan Wang, Yuhan Wu, Lei Cheng, Chao Zhao, Xuefei Li, Caicun Zhou; Received November 22, 2024 Accepted January 16, 2025 Published online January 20, 2025; DOI: https://doi.org/10.4143/crt.2024.1119 [Accepted]

Abstract PDF: Purpose
Investigate the role of lipid metabolism in the tumor immune microenvironment (TIME) of lung adenocarcinoma (LUAD) and identify vital lipid metabolism-related genes (LMRGs) that contribute to immunotherapy outcomes.
Materials and Methods
1130 LUAD patients were acquired utilizing public databases. Multiple algorithms were used to analyze the contribution of lipid metabolism in TIME. Importantly, cell lines, clinical samples (52 patients in surgery cohort and 36 in immunotherapy cohort), animal models, RNA-seq, experiments in protein and mRNA levels were conducted for identifying and validating key biomarker in LUAD immunotherapy.
Results
A prognostic signature comprising 33 LMRGs was developed and validated as an effective predictor of prognosis and TIME, with a C-index of 0.766 (95% CI: 0.729-0.804). Additionally, we identified Acyl-CoA Synthetase Long Chain Family Member 3 (ACSL3) as a potential biomarker for immunotherapy prognosis. The expression of ACSL3 was verified in 88 clinical tissues from LUAD patients, which indicated that elevated ACSL3 expression was correlated with worse progression-free survival (PFS) (p<0.001) and overall survival (OS) (p=0.008). Subsequent experiments revealed that knockdown of ACSL3 in vivo enhanced the efficacy of immunotherapy, potentially through increasing interferon α secretion, as indicated by Bulk RNA-seq and ELISA analysis, thereby promoting the infiltration of anti-tumor immune cells.
Conclusion
The study established a model that accurately predicts immunotherapy response, prognosis, and TIME dynamics in LUAD patients. Notably, the pivotal role of ACSL3 in driving tumor progression and immune evasion was uncovered, offering novel insights into the optimization of immunotherapy strategies for LUAD.

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Intercalated Treatment Following Rebiopsy Is Associated with a Shorter Progression-Free Survival of Osimertinib Treatment: Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kuo-Hsuan Hsu, Yen-Hsiang Huang, Kang-Yi Su, Sung-Liang Yu, Gee-Chen Chang; Cancer Res Treat. 2018;50(4):1164-1174. Published online December 11, 2017; DOI: https://doi.org/10.4143/crt.2017.460

Abstract PDF Supplementary Material PubReader ePub

Purpose
Epidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment.
Materials and Methods
Advanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients’ characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription.
Results
A total of 91 patients were enrolled, including 14 (15.4%) with primary and 77 (84.6%) with acquired T790M mutation. The objective response rate and disease controlratewere 60.9% and 85.1%, respectively. The median progression-free survival (PFS) and overall survival were 11.5 months (95% confidence interval [CI], 9.0 to 14.0) and 30.4 months (95% CI, 11.3 to 49.5), respectively. There was no significant difference in response rate and PFS between primary and acquired T790M populations. In the acquired T790M subgroup, patientswho received osimertinib after T790M had been confirmed by rebiopsy had a longer PFS than those with intercalated treatments between rebiopsy and osimertinib prescription (14.0 months [95% CI, 9.0 to 18.9] vs. 7.2 months [95% CI, 3.7 to 10.8]; adjusted hazard ratio, 0.48 [95% CI, 0.24 to 0.98; p=0.043]). Rebiopsy timing did not influence the outcome.
Conclusion
Osimertinib prescription with intercalated treatment following rebiopsy but not the timing of T790M emergence influenced the treatment outcome. We suggest that it is better to start osimertinib treatment once T790M mutation has been confirmed by biopsy.

Citations

Citations to this article as recorded by

Real-world osimertinib pretreatment experience in patients with epidermal growth factor receptor T790M mutation-positive locally advanced or metastatic non-small cell lung cancer
Gee-Chen Chang, Jin-Yuan Shih, Chong-Jen Yu, Heng-Sheng Chao, Cheng-Ta Yang, Chien-Chung Lin, Jen-Yu Hung, Sheng-Yen Hsiao, Chin-Chou Wang, Chih-Feng Chian, Te-Chun Hsia, Yuh-Min Chen, Chien-Feng Li
PLOS ONE.2024; 19(5): e0303046. CrossRef
Primary Tumor Resection Is Associated with a Better Outcome among Advanced EGFR-Mutant Lung Adenocarcinoma Patients Receiving EGFR-TKI Treatment
Jeng-Sen Tseng, Kuo-Hsuan Hsu, Zhe-Rong Zheng, Tsung-Ying Yang, Kun-Chieh Chen, Yen-Hsiang Huang, Kang-Yi Su, Sung-Liang Yu, Gee-Chen Chang
Oncology.2021; 99(1): 32. CrossRef
Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI
Chi-Lu Chiang, Hsu-Ching Huang, Chia-I Shen, Yung-Hung Luo, Yuh-Min Chen, Chao-Hua Chiu
Targeted Oncology.2020; 15(4): 503. CrossRef
Prior EGFR-TKI Treatment in EGFR-Mutated NSCLC Affects the Allele Frequency Fraction of Acquired T790M and the Subsequent Efficacy of Osimertinib
Chih-Hsi Scott Kuo, Chi-Hsien Huang, Chien-Ying Liu, Stelios Pavlidis, Ho-Wen Ko, Fu-Tsai Chung, Tin-Yu Lin, Chih-Liang Wang, Yi-Ke Guo, Cheng-Ta Yang
Targeted Oncology.2019; 14(4): 433. CrossRef

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EGFR Mutation Status in Lung Adenocarcinoma-Associated Malignant Pleural Effusion and Efficacy of EGFR Tyrosine Kinase Inhibitors: Jiyoul Yang, Ok-Jun Lee, Seung-Myoung Son, Chang Gok Woo, Yusook Jeong, Yaewon Yang, Jihyun Kwon, Ki Hyeong Lee, Hye Sook Han; Cancer Res Treat. 2018;50(3):908-916. Published online September 19, 2017; DOI: https://doi.org/10.4143/crt.2017.378

Abstract PDF PubReader ePub

Purpose
Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy.
Materials and Methods
Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKI‒treated patients were analyzed retrospectively.
Results
EGFR mutations were detected in 72.5% of LA-MPE cell blocks (29/40). The median progression-free survival for patients with EGFR mutations in LA-MPEs was better than that for patients with wild-type EGFR (7.33 months vs. 2.07 months; hazard ratio, 0.486; 95% confidence interval, 0.206 to 1.144; p=0.032). The objective response rate (ORR) of 26 patients with EGFR mutations in LA-MPEs among the 36 patients with measurable lesions was 80.8%, while the ORR of the 10 patients with wild-type EGFR in LA-MPEs was 10% (p < 0.001). Among the 26 patients with EGFR mutations in LA-MPEs, the ORR of target lesions and LA-MPEs were 88.5% and 61.5%, respectively (p=0.026).
Conclusion
EGFR mutation status in cell blocks of LA-MPEs confirmed by pathologic diagnosis is highly predictive of EGFR TKI efficacy. For patients with EGFR mutations in LA-MPEs, the response to EGFR TKIs seems to be worse for pleural effusions than for solid tumors.

Citations

Citations to this article as recorded by

Cancer‐associated fibroblast‐derived colony‐stimulating factor 2 confers acquired osimertinib resistance in lung adenocarcinoma via promoting ribosome biosynthesis
Yutang Huang, Xiaoqing Wang, Chunjie Wen, Jingchan Wang, Honghao Zhou, Lanxiang Wu
MedComm.2024;[Epub] CrossRef
Effect of chemotherapy, immunotherapy, and targeted therapies on removal of indwelling pleural catheters in non-small cell lung cancer patients with malignant pleural effusions
Melissa Wang, Kaitlin Sparrow, Chrystal Chan, Ashley Gillson, Daniel Stollery, Pen Li
Respiratory Medicine.2023; 206: 107093. CrossRef
Malignant pleural effusion diagnosis and therapy
Liangliang Yang, Yue Wang
Open Life Sciences.2023;[Epub] CrossRef
Failure pattern and radiotherapy exploration in malignant pleural effusion non-small cell lung cancer treated with targeted therapy
Qingsong Li, Cheng Hu, Shengfa Su, Zhu Ma, Yichao Geng, Yinxiang Hu, Huiqin Li, Bing Lu
Frontiers in Oncology.2023;[Epub] CrossRef
Impact of thoracic tumor radiotherapy on survival in non‐small‐cell lung cancer with malignant pleural effusion treated with targeted therapy: Propensity score matching study
Qingsong Li, Cheng Hu, Shengfa Su, Zhu Ma, Yichao Geng, Yinxiang Hu, Haijie Jin, Huiqin Li, Bing Lu
Cancer Medicine.2023; 12(14): 14949. CrossRef
EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery
Toshiya Fujiwara, Kazuhiko Shien, Motoki Matsuura, Junichi Soh, Hiromasa Yamamoto, Soshi Takao, Yuho Maki, Tsuyoshi Ueno, Ryujiro Sugimoto, Ken Suzawa, Mikio Okazaki, Hiroyuki Tao, Makio Hayama, Masafumi Kataoka, Yoshifumi Sano, Hidetoshi Inokawa, Motohir
Annals of Surgical Oncology.2023; 30(11): 6697. CrossRef
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Zihui Li, Jie Deng, Fei Yan, Li Liu, Yanling Ma, Jianhai Sun
Scientific Reports.2023;[Epub] CrossRef
Establishment of prognostic nomograms for predicting the progression free survival of EGFR‐sensitizing mutation, advanced lung cancer patients treated with EGFR‐TKIs
Xinyang Du, Hua Bai, Zhijie Wang, Jianchun Daun, Zheng Liu, Jiachen Xu, Geyun Chang, Yixiang Zhu, Jie Wang
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Wei Zhang, Wenjuan Han, Bo Yu, Xin Zhao, Gaojun Lu, Wendy Wu, Yi Zhang
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Julien Guinde, Hervé Dutau, Philippe Astoul
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Non-Small Cell Lung Cancer with Malignant Pleural Effusion May Require Primary Tumor Radiotherapy in Addition to Drug Treatment
Qingsong Li, Cheng Hu, Shengfa Su, Zhu Ma, Yichao Geng, Yinxiang Hu, Huiqin Li, Bing Lu
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Xinyi Li, Cong Huang, Xiaohui Xie, Ziyang Wu, Xia Tian, Yibo Wu, Xin Du, Luwen Shi
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Risk Factors for and Time to Recurrence of Symptomatic Malignant Pleural Effusion in Patients With Metastatic Non-Small Cell Lung Cancer with EGFR or ALK Mutations
Audra J. Schwalk, David E. Ost, Sahara N. Saltijeral, Henriette De La Garza, Roberto F. Casal, Carlos A. Jimenez, Georgie A. Eapen, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Jack Lee, Yasir Elamin, Jianjun Zhang, Jack A. Roth, Stephen S
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