Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Discrepancy between Genetically Predicted and Observed Alcohol Intake and Its Impact on Gastric Cancer Susceptibility: Ga-Eun Yie, Cheol Min Shin, Kyungtaek Park, Jinyeon Jo, Ah Ra Do, Sungkyoung Choi, Jung Hun Ohn, Sejoon Lee, Jeongseon Kim, Sun Ha Jee, Seung Joo Kang, Nayoung Kim, Sungho Won; Cancer Res Treat. 2026;58(2):563-572. Published online May 30, 2025; DOI: https://doi.org/10.4143/crt.2025.109

Abstract PDF Supplementary Material PubReader ePub: Purpose
We aimed to investigate how genetic predisposition to drinking and gastric cancer (GC) modifies the association between alcohol consumption and GC risk in the Korean population.
Materials and Methods
Polygenic risk scores for GC (PRS-GC) and alcohol consumption (PRS-Alcohol) were formulated using genome-wide association results from BioBank Japan. Validation was performed using Korean cohorts (SNUBH-GENIE cohort), incorporating 8,846 controls and 531 patients with GC. Subsequently, these PRSs were applied to an independent Korean cohort of 67,771 participants, including 313 patients with GC during the follow-up for 14 years (KoGES cohort).
Results
In KoGES cohort, the influence of alcohol consumption on GC risk was significantly altered by the PRS-GC and exhibited a synergistic interaction effect. PRS-Alcohol itself shows a negative correlation with GC risk. However, when actual alcohol consumption significantly exceeded genetically predicted levels, the risk of alcohol-related GC was notably increased (adjusted hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.72). Heavy drinkers in the high–PRS-GC/low–PRS-Alcohol group had a 2.16 times higher risk of GC than non-to-light drinkers, which was prominent in males.
Conclusion
Korean drinkers with higher PRS-GC who consume alcohol more than genetically predicted levels are susceptible to GC. PRS-GC and PRS-Alcohol may be beneficial for assessing the impact of alcohol consumption on GC risk in Koreans.

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Lung and Thoracic cancer

Association of TP53 Mutation Status and Sex with Clinical Outcome in Non–Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study: Songji Choi, Se Hyun Kim, Sejoon Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jin Won Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee; Cancer Res Treat. 2025;57(1):70-82. Published online August 7, 2024; DOI: https://doi.org/10.4143/crt.2024.046

Abstract PDF Supplementary Material PubReader ePub

Purpose
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results
In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Citations

Citations to this article as recorded by

Unraveling the nexus: Tumor mutational burden, PD‐L1 expression, and oncogenic alterations in non–small cell lung cancer cytology specimens
Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P. Patel, Asif Rashid, Shun Rao, Mark J. Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy‐Chowd
Cancer Cytopathology.2026;[Epub] CrossRef
TP53 MUTATIONAL STATUS AND SMOKING HISTORY AS PREDICTORS OF THE EFFICACY OF IMMUNOTHERAPY AND CHEMOIMMUNOTHERAPY IN METASTATIC NON-SMALL CELL LUNG CANCER
V. V. Budko, V. Y. Prostatina, Y. V. Moskalenko
Актуальні проблеми сучасної медицини: Вісник Української медичної стоматологічної академії.2026; 26(2): 5. CrossRef
Association Between TP53 Mutations and Platinum Resistance in a Cohort of High-Grade Serous Ovarian Cancer Patients: Novel Implications for Personalized Therapeutics
Clelia Madeddu, Eleonora Lai, Manuela Neri, Elisabetta Sanna, Giulia Gramignano, Sonia Nemolato, Mario Scartozzi, Sabrina Giglio, Antonio Macciò
International Journal of Molecular Sciences.2025; 26(5): 2232. CrossRef
Prognostic and predictive implications of tumor suppressor gene alterations in non-small cell lung cancer
Marco Sposito, Lorenzo Belluomini, Riccardo Nocini, Jessica Insolda, Ilaria Mariangela Scaglione, Jessica Menis, Michele Simbolo, Antonio Lugini, Federica Buzzacchino, Francesco Verderame, Francesca Spinnato, Giuseppe Aprile, Lorenzo Calvetti, Mario Occhi
Scientific Reports.2025;[Epub] CrossRef
Enhanced tumor heterogeneity mediates poor prognosis in females with TP53 mutation in lung adenocarcinoma
Liudan Mai, Xinxin Yang, Chen Shao, Hongwei Yu, Fenqi Du, Jialu Liu, Yue Guan, Hao Li, Maopeng Yang, Hongxue Meng, Qiuju Zhang
International Journal of Biological Macromolecules.2025; 334: 149083. CrossRef

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Genomic Landscape of Pulmonary Sarcomatoid Carcinoma: Hyun Jung Kwon, Sejoon Lee, Yeon Bi Han, Jeonghyo Lee, Soohyeon Kwon, Hyojin Kim, Jin-Haeng Chung; Cancer Res Treat. 2024;56(2):442-454. Published online November 14, 2023; DOI: https://doi.org/10.4143/crt.2023.764

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pulmonary sarcomatoid carcinoma (PSC) is a rare aggressive subtype of non–small cell lung cancer (NSCLC) with limited therapeutic strategies. We attempted to elucidate the evolutionary trajectories of PSC using multiregional and longitudinal tumor samples.
Materials and Methods
A total of 31 patients were enrolled in this study and 11 longitudinal samples were available from them. Using whole exome sequencing data, we analyzed the mutational signatures in both carcinomatous and sarcomatous areas in primary tumors of the 31 patients and longitudinal samples obtained from 11 patients. Furthermore, digital droplet polymerase chain reaction (ddPCR), and programmed death-ligand 1 (PD-L1) immunohistochemistry using the Ventana SP263 assay were performed.
Results
TP53 was identified as the most frequently altered gene in the primary (74%) and metastatic (73%) samples. MET exon 14 skipping mutations, confirmed by ddPCR, and TP53 mutations were mutually exclusive; whereas, MET exon 14 skipping mutations frequently co-occurred with MDM2 amplification. Metastatic tumors showed dissimilar genetic profiles from either primary component. During metastasis, the signatures of APOBEC decreased in metastatic lesions compared with that in primary lesions. PSC showed higher MET and KEAP1 mutations and stronger PD-L1 protein expression compared with that recorded in other NSCLCs.
Conclusion
Decreased APOBEC signatures and subclonal diversity were detected during malignant progression in PSC. Frequent MET mutations and strong PD-L1 expression distinguished PSC from other NSCLCs. The aggressiveness and therapeutic difficulties of PSC were possibly attributable to profound intratumoral and intertumoral genetic diversity. Next-generation sequencing could suggest the appropriate treatment strategy for PSC.

Citations

Citations to this article as recorded by

A Phase II Study of Durvalumab, Doxorubicin, and Ifosfamide in Recurrent and/or Metastatic Pulmonary Sarcomatoid Carcinoma (KCSG LU-19-24)
Miso Kim, Jeonghwan Youk, Tae Min Kim, Gyeong-Won Lee, Dong-Wan Kim, Bhumsuk Keam
Clinical Lung Cancer.2026; 27(3): 58. CrossRef
Genomic characterization of pulmonary sarcomatoid adenocarcinoma: a paired whole-exome sequencing study of carcinomatous and sarcomatous components
Jing Lin, Yuzhong Yang, Mengqing Liu, Fan Yang, Shaofeng Jiang, Longkuan Xu, Xiang Zheng, Hui Wei, Xuyan Wen, Guining Xu, Ruolan Weng, Jinhua Zheng, Shengjun Xiao
Frontiers in Oncology.2026;[Epub] CrossRef
Prevalence of High Programmed Death-Ligand 1 Expression in Pulmonary Sarcomatoid Carcinoma: A Systematic Review and Meta-Analysis
Yusuke Hamakawa, Aya Shiba, Yohei Noguchi, Hiroyuki Shinohara, Yuko Higashi, Masaharu Aga, Kazuhito Miyazaki, Yuri Taniguchi, Yuki Misumi, Yoko Agemi, Tsuneo Shimokawa, Hiroaki Okamoto, Nobuyuki Horita, Yukiko Nakamura
JTO Clinical and Research Reports.2026; 7(10): 101046. CrossRef
Pulmonary pleomorphic carcinoma associated with cystic airspace and recurrent spontaneous pneumothorax: A case report
Qiangsheng Li, Jing Zhang, Youjie Gong, Xudong Wan, Song Zhang, Zhongwang Li, Jun Liu
Oncology Letters.2025; 30(1): 1. CrossRef
Combination of epirubicin and cyclophosphamide for the treatment of advanced pulmonary sarcomatoid carcinoma: A case report and literature review
Ruoyu Deng, Jialing Lv, Fang Wang, Yanqiong Chen, Junfeng Wang, Lin Wang, Lixia Mu, Zhijun Zhang, Wen Zhang, Chao Zhang
Journal of Cancer Research and Therapeutics.2025; 21(2): 512. CrossRef
Challenges in the Recognition and Management of Metastatic Sarcomatoid Carcinoma Masquerading As Post-traumatic Hematoma
Abigayle Wyer, Mena Louis, Richard Adams, Raven Richardson, Ezra Ellis, Brian Gibson
Cureus.2025;[Epub] CrossRef
Distinct Clinicogenomic Features and Immunotherapy Associations in Pulmonary Sarcomatoid Carcinoma: A Multicenter Retrospective Study
Lingzhi Hong, Alessandro Di Federico, Bolun Liu, Alissa J. Cooper, Joao V. Alessi, Phoebe Clark, Waree Rinsurongkawong, Chingyi Young, Hui Li, Kang Qin, Muhammad Aminu, Valentina Santo, Yasir Elamin, Boris Sepesi, Jeff Lewis, Don L. Gibbons, Ara A. Vaporc
Journal of Thoracic Oncology.2025; 20(12): 1763. CrossRef
Exceptional Response to Immunotherapy-based Treatment in Compound EGFR-Mutated Oligometastatic Pulmonary Sarcomatoid Carcinoma: A Case Report
Ayushi Gianchandani, Darshana Desai, Janani Sambath, Darshana Patil, Prashant Kumar, Shambhavi Singh, Chetan Madre, Ruturaj Deshpande, Anjali Parab, Niyati Shah, Darshit Shah, Pritam Kataria, Shrikanth Atluri, Marzi Mehta, Aditya Shreenivas, Rajan Datar,
Journal of Immunotherapy and Precision Oncology.2025; 8(3): 206. CrossRef
Immune Checkpoint Inhibitor Monotherapy for Patients With Pulmonary Sarcomatoid Carcinoma—The Optimal Therapeutic Strategy for This Rare Lung Cancer Subtype?
Jennifer M. Boland, Ying-Chun Lo, Aaron S. Mansfield
Journal of Thoracic Oncology.2025; 20(12): 1735. CrossRef
PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma
Shipra Agarwal, Chan Kwon Jung, Pranitha Gaddam, Mitsuyoshi Hirokawa, Takuya Higashiyama, Jen-Fan Hang, Wei-An Lai, Somboon Keelawat, Zhiyan Liu, Hee Young Na, So Yeon Park, Junya Fukuoka, Shinya Satoh, Zhanna Mussazhanova, Masahiro Nakashima, Kennichi Ka
American Journal of Surgical Pathology.2024; 48(10): 1233. CrossRef

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