Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Effector Function Characteristics of Exhausted CD8+ T-Cell in Microsatellite Stable and Unstable Gastric Cancer: Dong-Seok Han, Yoonjin Kwak, Seungho Lee, Soo Kyung Nam, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Nak-Jung Kwon, Hye Seung Lee, Han-Kwang Yang; Cancer Res Treat. 2024;56(4):1146-1163. Published online April 12, 2024; DOI: https://doi.org/10.4143/crt.2024.317

Purpose
Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability–high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors, presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential.
Materials and Methods
We explored the molecular characteristics of CD8+ T-cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis.
Results
In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T cell and natural killer T cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The interferon γ (IFN-γ) signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer.
Conclusion
Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.

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Simvastatin induces ferroptosis and activates anti-tumor immunity to sensitize anti-PD-1 immunotherapy in microsatellite stable gastric cancer
Yumei Ning, Shilin Fang, Runan Zhang, Jun Fang, Kun Lin, Yang Ding, Haihang Nie, Jingkai Zhou, Qiu Zhao, Hengning Ke, Haizhou Wang, Fan Wang
International Immunopharmacology.2024; 142: 113244. CrossRef

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Identification of New Pathogenic Variants of Hereditary Diffuse Gastric Cancer: Seung-Young Oh, Giyong Jang, Jaeryuk Kim, Kyoung-Yun Jeong, Hyun Myong Kim, Yoon Jin Kwak, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Sung-Yup Cho, Jong-Il Kim, Han-Kwang Yang; Cancer Res Treat. 2024;56(4):1126-1135. Published online April 11, 2024; DOI: https://doi.org/10.4143/crt.2024.328

Abstract PDF PubReader ePub

Purpose
Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression.
Materials and Methods
Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation, and enrichment analysis were performed.
Results
As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in-silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the Rhoa^R129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked Rhoa^R129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families.
Conclusion
The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.

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Current advances and challenges in Managing Hereditary Diffuse Gastric Cancer (HDGC): a narrative review
L. van der Sluis, J.M. van Dieren, R.S. van der Post, T.M. Bisseling
Hereditary Cancer in Clinical Practice.2024;[Epub] CrossRef

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Gastrointestinal Cancer

Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy: Bang Wool Eom, Joongyub Lee, In Seob Lee, Young-Gil Son, Keun Won Ryu, Sung Geun Kim, Hyoung-Il Kim, Young-Woo Kim, Seong-Ho Kong, Oh Kyoung Kwon, Ji-Ho Park, Ji Yeong An, Chang Hyun Kim, Byoung-Jo Suh, Hong Man Yoon, Myoung Won Son, Ji Yeon Park, Jong-Min Park, Sang-Ho Jeong, Moon-Won Yoo, Geum Jong Song, Han-Kwang Yang, Yun-Suhk Suh, Ki Bum Park, Sang-Hoon Ahn, Dong Woo Shin, Ye Seob Jee, Hye-Seong Ahn, Sol Lee, Jae Seok Min, Haejin In, Ahyoung Kim, Hoon Hur, Hyuk-Joon Lee, on behalf of KOrean QUality of life in Stomach cancer patients Study group (KOQUSS); Cancer Res Treat. 2021;53(3):763-772. Published online December 29, 2020; DOI: https://doi.org/10.4143/crt.2020.1270

Abstract PDF Supplementary Material PubReader ePub

Purpose
Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity.
Results
The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.

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Global status of research on gastrointestinal cancer patients’ quality of life: A bibliometric and visual analysis from 2003 to 2023
Xiaoqin Wang, Caihua Wang, Wenjin Han, Jiaru Sun, Zhaozhao Hui, Shuangyan Lei, Huili Wu, Xiaohong Liu
Heliyon.2024; 10(1): e23377. CrossRef
Development and Feasibility Assessment of Mobile Application-Based Digital Therapeutics for Postoperative Supportive Care in Gastric Cancer Patients Following Gastrectomy
Ji-Hyeon Park, Hyuk-Joon Lee, JeeSun Kim, Yo-Seok Cho, Sunjoo Lee, Seongmin Park, Hwinyeong Choe, Eunhwa Song, Youngran Kim, Seong-Ho Kong, Do Joong Park, Byung-Ho Nam, Han-Kwang Yang
Journal of Gastric Cancer.2024; 24(4): 420. CrossRef
Effect of Four Main Gastrectomy Procedures for Proximal Gastric Cancer on Patient Quality of Life: A Nationwide Multi-Institutional Study
Koji Nakada, Akitoshi Kimura, Kazuhiro Yoshida, Nobue Futawatari, Kazunari Misawa, Kuniaki Aridome, Yoshiyuki Fujiwara, Kazuaki Tanabe, Hirofumi Kawakubo, Atsushi Oshio, Yasuhiro Kodera
Journal of Gastric Cancer.2023; 23(2): 275. CrossRef
Quality of life after gastric cancer surgery
Jae Kyun Park, Hyuk-Joon Lee
Foregut Surgery.2023; 3(2): 27. CrossRef
Long-term Functional and Patient-reported Outcomes Between Intra-corporeal Delta-shaped Gastroduodenostomy and Gastrojejunostomy After Laparoscopic Distal Gastrectomy
Sin Hye Park, Hong Man Yoon, Keun Won Ryu, Young-Woo Kim, Mira Han, Bang Wool Eom
Journal of Gastric Cancer.2023; 23(4): 561. CrossRef
Potential Applicability of Local Resection With Prophylactic Left Gastric Artery Basin Dissection for Early-Stage Gastric Cancer in the Upper Third of the Stomach
Yoshimasa Akashi, Koichi Ogawa, Katsuji Hisakura, Tsuyoshi Enomoto, Yusuke Ohara, Yohei Owada, Shinji Hashimoto, Kazuhiro Takahashi, Osamu Shimomura, Manami Doi, Yoshihiro Miyazaki, Kinji Furuya, Shoko Moue, Tatsuya Oda
Journal of Gastric Cancer.2022; 22(3): 184. CrossRef
Systematic review of health-related quality of life (HRQoL) issues associated with gastric cancer: capturing cross-cultural differences
Alison Rowsell, Samantha C. Sodergren, Vassilios Vassiliou, Anne-Sophie Darlington, Marianne G. Guren, Bilal Alkhaffaf, Chantelle Moorbey, Kristopher Dennis, Mitsumi Terada
Gastric Cancer.2022; 25(4): 665. CrossRef
Patient-reported gastrointestinal symptoms following surgery for gastric cancer and the relative risk factors
Rui Xu, Qiong Gu, Shuomeng Xiao, Ping Zhao, Zhi Ding
Frontiers in Oncology.2022;[Epub] CrossRef
Prospective multicentre randomised clinical trial comparing survival rates, quality of life and nutritional status between advanced gastric cancer patients with different follow-up intensities: study protocol for the STOFOLUP trial
Bang Wool Eom, Dong-Hoe Koo, Ji Yeong An, Han Hong Lee, Hyoung-Il Kim, Hoon Hur, Moon-Won Yoo, Min-Hee Ryu, Hyuk-Joon Lee, Su Mi Kim, Ji-Ho Park, Jae Seok Min, Kyung Won Seo, Sang-Ho Jeong, Oh Jeong, Oh Kyoung Kwon, Seung Wan Ryu, Chang Hak Yoo, Jae Moon
BMJ Open.2021; 11(12): e056187. CrossRef

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Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis: Yun-Suhk Suh, Jieun Yu, Byung Chul Kim, Boram Choi, Tae-Su Han, Hye Seong Ahn, Seong-Ho Kong, Hyuk-Joon Lee, Woo Ho Kim, Han-Kwang Yang; Cancer Res Treat. 2015;47(4):718-726. Published online February 2, 2015; DOI: https://doi.org/10.4143/crt.2014.064

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis.
Materials and Methods
Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed ≥ 2-fold differential expression and were significant by Welch's t test (p < 0.05) between highN and lowN. Those selected genes were validated independently by reverse- transcriptase–polymerase chain reaction (RT-PCR) using five AGC patients, and tissue- microarray (TMA) comprising 47 AGC patients.
Results
CFTR, LAMC2, SERPINE2, F2R, MMP7, FN1, TIMP1, plasminogen activator inhibitor-1 (PAI- 1), ITGB8, SDS, and TMPRSS4 were commonly up-regulated over 2-fold in highN. REG3A, CD24, ITLN1, and WBP5 were commonly down-regulated over 2-fold in lowN. Among these genes, overexpression of PAI-1 was validated by RT-PCR, and TMA showed 16.7% (7/42) PAI-1 expression in T3N3, but none (0/5) in T4N0 (p=0.393).
Conclusion
DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC.

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Expression of Serpin Family E Member 1 (SERPINE1) Is Associated with Poor Prognosis of Gastric Adenocarcinoma
Jie Lv, Chunyang Yu, Hanhan Tian, Tao Li, Changhua Yu
Biomedicines.2023; 11(12): 3346. CrossRef
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Wei Cheng, Yonghui Liao, Yuan Xie, Qinrong Wang, Leilei Li, Yuanjia Chen, Yan Zhao, Jianjiang Zhou
Cancer Cell International.2023;[Epub] CrossRef
Analysis of CFTR gene expression as an immunological and prognostic biomarker in pan-cancers
Qi Wang, Shubing Jia, Jie Zheng, Rongwu Xiang, Yong Cui, Jinghai Zhang, Yijia Xu, Mingyi Zhao
Computers in Biology and Medicine.2022; 146: 105614. CrossRef
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Xueshu Chen, Wei Chen, Yan Zhao, Qinrong Wang, Wenling Wang, Yining Xiang, Hang Yuan, Yuan Xie, Jianjiang Zhou
Journal of Translational Medicine.2022;[Epub] CrossRef
SERBP1 affects the apoptotic level by regulating the expression and alternative splicing of cellular and metabolic process genes in HeLa cells
Junjie Zhou, Wenhao Chen, Qianwen He, Dong Chen, Chunguang Li, Congqing Jiang, Zhao Ding, Qun Qian
PeerJ.2022; 10: e14084. CrossRef
A qualitative transcriptional signature of recurrence risk for stages II–III gastric cancer patients after surgical resection
Huarong Zhang, Xiangyu Li, Junling Wu, Jiahui Zhang, Haiyan Huang, Yawei Li, Meifeng Li, Shanshan Wang, Jie Xia, Lishuang Qi, Ting Chen, Lu Ao
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Qiaoyun Zhao, Jun Xie, Jinliang Xie, Rulin Zhao, Conghua Song, Huan Wang, Jianfang Rong, Lili Yan, Yanping Song, Fangfei Wang, Yong Xie
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C.R. Akshatha, Smitha Bhat, R. Sindhu, Dharini Shashank, Sarana Rose Sommano, Wanaporn Tapingkae, Ratchadawan Cheewangkoon, Shashanka K. Prasad
Saudi Journal of Biological Sciences.2021; 28(9): 5371. CrossRef
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Gary Tincknell, Ann-Katrin Piper, Morteza Aghmesheh, Therese Becker, Kara Lea Vine, Daniel Brungs, Marie Ranson
Cancers.2021; 13(16): 4097. CrossRef
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H.M.C. Kumara, Addison Poppy, Dasuni Gamage, Erica Pettke, Abhinit Shah, Xiaohong Yan, Vesna Cekic, Richard Whelan
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C. Ward, P. Cauchy, P. Garcia, J. Frampton, M. A. Esteban, G. Volpe
Scientific Reports.2020;[Epub] CrossRef
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Journal of Cellular Biochemistry.2020; 121(2): 1911. CrossRef
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Si-Jing Li, Xiao-Hui Wei, Xiao-Man Zhan, Jin-Yong He, Yu-Qi Zeng, Xue-Mei Tian, Sheng-Tao Yuan, Li Sun
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Bodong Xu, Zhigang Bai, Jie Yin, Zhongtao Zhang
PeerJ.2019; 7: e7091. CrossRef
Role of ion channels in gastrointestinal cancer
Kyle J Anderson, Robert T Cormier, Patricia M Scott
World Journal of Gastroenterology.2019; 25(38): 5732. CrossRef
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Yangyang Qian, Zongfu Pan, Zhenying Guo, Xinyang Ge, Guowan Zheng, Jun Cao, Ping Huang, Xin Zhu, Xuhang Zhu, Qingliang Wen, Minghua Ge
BioMed Research International.2019; 2019: 1. CrossRef
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Jieting Zhang, Yan Wang, Xiaohua Jiang, Hsiao Chang Chan
Cellular and Molecular Life Sciences.2018; 75(10): 1737. CrossRef
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Journal of Pharmaceutical and Biomedical Analysis.2018; 160: 344. CrossRef
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Arseniy E. Yuzhalin, Su Yin Lim, Anton G. Kutikhin, Alex N. Gordon-Weeks
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Hengchun Zhang, Zhiguo Sun, Yan Li, Dong Fan, Hao Jiang
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