Cancer Research and Treatment

Original Articles

Microbial Dynamics Across Molecular Subtypes and Prognostic Significance of Lactobacillus in Gastric Cancer: Soo Kyung Nam, Juhyeong Park, Sujin Oh, Yoonjin Kwak, Cheol Min Shin, Kyoung Un Park, Nak-Jung Kwon, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee; Received April 25, 2025 Accepted July 16, 2025 Published online July 17, 2025; DOI: https://doi.org/10.4143/crt.2025.449 [Accepted]

Abstract PDF: Purpose
Recent studies have revealed a diverse gastric microbiota beyond Helicobacter pylori, suggesting a role in gastric cancer (GC). We aimed to investigate the composition and characteristics of the microbiota in GC and non-cancerous gastric mucosa (NC), with a particular focus on their relationship to molecular subtypes.
Materials and Methods
We conducted 16S rRNA sequencing and whole transcriptomic analysis on fresh-frozen GC and NC tissue samples from 192 GC patients, as well as saliva samples from 12 GC patients and 18 healthy individuals. Microsatellite instability (MSI), Epstein-Barr virus (EBV) in situ hybridization, and immunohistochemistry for p53 and E-cadherin were used to define molecular subtypes.
Results
GC tissues exhibited significantly higher diversity compared to matched NC tissues, with microbial profiles marked by decreased Helicobacter and increased Streptococcus, Prevotella, and Lactobacillus. Saliva samples predominantly contained oral bacteria and exhibited distinct microbial profiles from gastric tissues. In GC tissue, Helicobacter abundance was negatively correlated with key immune checkpoint genes (CTLA-4, PDCD1, CD274, and LAG3), whereas Prevotella, Streptococcus, and Fusobacterium were positively correlated. MSI-high and EBV-positive subtypes showed lower levels of Helicobacter but higher levels of Lactobacillus, Prevotella, and Streptococcus compared to the epithelial-mesenchymal transition (EMT)-like subtype. Notably, within MSI-H GC, a subgroup characterized by Lactobacillus-enriched and otherwise microbiota-depleted profiles was significantly associated with poorer overall and disease-free survival.
Conclusion
These findings underscore distinct microbial patterns across GC molecular subtypes, suggesting potential biomarkers for GC diagnosis and treatment.

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Gastrointestinal cancer

Detection Ability of Quality of Life Changes and Responsiveness of the KOQUSS-40 and the EORTC QLQ-C30/STO22 in Patients Who Underwent Gastrectomy: A Prospective Comparative Study: Bang Wool Eom, Keun Won Ryu, Ji Yeong An, Yun-Suhk Suh, In Cho, Sung Geun Kim, Ji-Ho Park, Hoon Hur, Hyung-Ho Kim, Sang-Hoon Ahn, Sun-Hwi Hwang, Hong Man Yoon, Ki Bum Park, Hyoung-Il Kim, In-Gyu Kwon, Han-Kwang Yang, Byoung-Jo Suh, Sang-Ho Jeong, Tae-Han Kim, Oh Kyoung Kwon, Hye-Seong Ahn, Ji Yeon Park, Ki Young Yoon, Myoung Won Son, Seong-Ho Kong, Young-Gil Son, Geum Jong Song, Jong Hyuk Yun, Jung-Min Bae, Do Joong Park, Sol Lee, Jun-Young Yang, Kyung Won Seo, You-Jin Jang, So Hyun Kang, Joongyub Lee, Hyuk-Joon Lee, on behalf of KOrean QUality of life in Stomach cancer patients Study group (KOQUSS); Cancer Res Treat. 2026;58(1):221-231. Published online March 5, 2025; DOI: https://doi.org/10.4143/crt.2024.1104

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Purpose
The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ).
Materials and Methods
A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire.
Results
Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ.
Conclusion
KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

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The efficacy of early progressive resistance exercise in the postoperative management of pancreaticoduodenectomy for pancreatic cancer: a randomized controlled trial
Xuexue Liu, Neng Shi, Rui Li, Yuan Song
Frontiers in Surgery.2025;[Epub] CrossRef
Improvement in Quality of Life After Early Interactive Human Coaching via a Mobile App in Postgastrectomy Patients With Gastric Cancer: Prospective Randomized Controlled Trial
Bang Wool Eom, Mira Han, Hong Man Yoon, Young-Woo Kim, So Young Kim, Jin Myoung Oh, Gyung Ah Wie, Keun Won Ryu
JMIR mHealth and uHealth.2025; 13: e75445. CrossRef

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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

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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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Gallic acid potentiates the tumour-killing function of CD8+ T cells in gastric cancer
Si Chen, HaiBin Wang, Meixu Lei, Yumin Li, Qi Wang, Hengxin Wang, Yifei Shen, Xuejie Su, Yali Zhou
Journal of Pharmacy and Pharmacology.2026;[Epub] CrossRef
Neurogranin facilitates maintaining the immunosuppressive state of hepatocellular carcinoma by promoting TGF-β1 secretion
Dongjie Ye, Zhu Zhang, Yuxin Yao, Banglun Pan, Hao Wu, Xinyu Zhang, Xiaoqian Wang, Nanhong Tang
International Journal of Biological Macromolecules.2025; 311: 143716. CrossRef
T-cell senescence: Unlocking the tumor immune “Dark Box” - A multidimensional analysis from mechanism to tumor immunotherapeutic intervention
Jia Cheng, Jian Zheng, Chen Ma, Yongzhang Li, Hua Hao
Seminars in Cancer Biology.2025; 113: 190. CrossRef
Hybrid model for predicting microsatellite instability in colorectal cancer using hematoxylin & eosin-stained images and clinical features
Hangping Wei, Xiaowei Zhang, Zhen Zhou, Jianbin Xie, Weidong Han, Xiaofang Dong
Frontiers in Oncology.2025;[Epub] CrossRef
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

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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.

Citations

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Hereditary diffuse gastric cancer: the evolution of a cancer syndrome
Lyvianne Decourtye-Espiard, Tanis Godwin, Parry Guilford
Journal of the Royal Society of New Zealand.2025; 55(6): 2636. CrossRef
A Comprehensive Review of Genetic Mutations Occurring in the Development and Progression of Gastric Cancer
Yalan Li, Qianqian Xu, Zhuo Chen, Mengting Chen, Kunyu Han, Zhuqing Zhang, Aling Shen, Xiaoyan Fu
Digestive Diseases.2025; 43(6): 630. CrossRef
Helicobacter pylori infection status and evolution of gastric cancer
Wenlin Zhang, Yuxin Zhang, Jing Ning, Weiwei Fu, Shigang Ding
Chinese Medical Journal.2025; 138(23): 3083. CrossRef
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

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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.

Citations

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Detection Ability of Quality of Life Changes and Responsiveness of the KOQUSS-40 and the EORTC QLQ-C30/STO22 in Patients Who Underwent Gastrectomy: A Prospective Comparative Study
Bang Wool Eom, Keun Won Ryu, Ji Yeong An, Yun-Suhk Suh, In Cho, Sung Geun Kim, Ji-Ho Park, Hoon Hur, Hyung-Ho Kim, Sang-Hoon Ahn, Sun-Hwi Hwang, Hong Man Yoon, Ki Bum Park, Hyoung-Il Kim, In-Gyu Kwon, Han-Kwang Yang, Byoung-Jo Suh, Sang-Ho Jeong, Tae-Han
Cancer Research and Treatment.2026; 58(1): 221. CrossRef
Function Preserving Gastrectomy and Quality of Life
Jeesun Kim, Hyuk-Joon Lee
Journal of Gastric Cancer.2025; 25(1): 247. CrossRef
Is Braun Jejunojejunostomy Necessary? Comparison Between Billroth-II Alone and Billroth-II With Braun Anastomosis After Distal Gastrectomy
Jane Chungyoon Kim, Min Jung Lee, Hyuk-Joon Lee, Kyoyoung Park, Min Kyu Kang, Sa-Hong Kim, Chun Zhuang, Abdullah Almayouf, Ma. Jeanesse C. Bernardo, Jeesun Kim, Yo-Seok Cho, Seong-Ho Kong, Soo-Jeong Cho, Do Joong Park, Han-Kwang Yang
Journal of Gastric Cancer.2025; 25(2): 318. CrossRef
Laparoscopic Pylorus-preserving Gastrectomy Versus Distal Gastrectomy for Early Gastric Cancer
Hyuk-Joon Lee, Young-Woo Kim, Do Joong Park, Sang Uk Han, Keun Won Ryu, Hyung-Ho Kim, Woo Jin Hyung, Ji-Ho Park, Yun-Suhk Suh, Oh-Kyung Kwon, Wook Kim, Young-Kyu Park, Hong Man Yoon, Sang-Hoon Ahn, Seong-Ho Kong, Han-Kwang Yang
Annals of Surgery.2025; 281(4): 573. CrossRef
Prospective Multicenter Observational Study on Postoperative Quality of Life According to Type of Gastrectomy for Gastric Cancer
Sung Eun Oh, Yun-Suhk Suh, Ji Yeong An, Keun Won Ryu, In Cho, Sung Geun Kim, Ji-Ho Park, Hoon Hur, Hyung-Ho Kim, Sang-Hoon Ahn, Sun-Hwi Hwang, Hong Man Yoon, Ki Bum Park, Hyoung-Il Kim, In Gyu Kwon, Han-Kwang Yang, Byoung-Jo Suh, Sang-Ho Jeong, Tae-Han Ki
Journal of Gastric Cancer.2025; 25(2): 382. CrossRef
The efficacy of a symptom management platform among gastric cancer survivors: a study protocol for a randomized controlled trial
Jeong Ho Song, Joongyub Lee, Jae Seok Min, Hyungkook Yang, Jong Hyuk Yun, Hayemin Lee, Eun Young Kim, Su Mi Kim, Sol Lee, Ki Bum Park, Geum Jong Song, Ji Ho Park, Bang Wool Eom, Hoon Hur, Sang Ho Jeong
International Journal of Surgery Protocols.2025; 29(3): 73. CrossRef
Gastrointestinal Sistem Kanserli Hastalarda Öz Yeterlilik İle Yaşam Kalitesi Arasındaki İlişki
Ezgi Karadağ, Yağmur Yaşa, Özlem Uğur
Etkili Hemşirelik Dergisi.2025; 18(4): 593. CrossRef
Symptoms, nutritional outcomes and quality of life after total gastrectomy with Roux-en-Y reconstruction: results of a cross-sectional study conducted on 80 long-term survivors
Annamaria Agnes, Alberto Biondi, Marina Carannante, Antonia Strippoli, Francesco Belia, Laura Lorenzon, Roberto Pezzuto, Flavio Tirelli, Lorenzo Ferri, Ilaria Neri, Domenico D’Ugo, Roberto Persiani
Updates in Surgery.2025;[Epub] CrossRef
Validation of a dietary intake questionnaire through nutritional markers and clinical outcomes in patients with gastric cancer following gastrectomy
Tae-Han Kim, Ji-Ho Park, Eun-Jung Jung, Taejin Park, Jin-Kwon Lee, Young-Hye Kim, Young-Joon Lee, Sang-Ho Jeong
Medicine.2025; 104(50): e46469. CrossRef
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
REsolution of Symptoms afTer Oesophago-gastric cancer REsection delphi (RESTOREd)—standardizing the definition, investigation and management of gastrointestinal symptoms and conditions after surgery
Ben E Byrne, Kwabena Siaw-Acheampong, Orla Evans, Joanna Taylor, Fiona Huddy, Magnus Nilsson, Ewen A Griffiths, Donald Low, James Gossage, Jason Dunn, Sebastian Zeki, Sheraz Markar, Kerry Avery, Jane M Blazeby, Andrew Cockbain, Charlotte Moss, Mieke van H
British Journal of Surgery.2024;[Epub] CrossRef
Surgical decisions and quality of life after gastrectomy for gastric cancer: update from Asian studies
Jia-yi Xu, Dong-yi Yan, Ren-hao Hu, Shun Zhang, Xiao-hua Jiang
Gastrointestinal Tumors.2024;[Epub] 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
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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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