Prognostic Impact of Stromal Profiles Educated by Gastric Cancer,Annals of Surgical Oncology

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Prognostic Impact of Stromal Profiles Educated by Gastric Cancer
Annals of Surgical Oncology ( IF 3.4 ) Pub Date : 2023-11-02 , DOI: 10.1245/s10434-023-14522-z
Kazunori Takahashi ₁ , Katsutoshi Shoda ₁ , Koichi Takiguchi ₁ , Yudai Higuchi ₁ , Koichi Matsuoka ₁ , Takashi Nakayama ₁ , Ryo Saito ₁ , Suguru Maruyama ₁ , Yuki Nakata ₁ , Shinji Furuya ₁ , Kensuke Shiraishi ₁ , Hidenori Akaike ₁ , Yoshihiko Kawaguchi ₁ , Hidetake Amemiya ₁ , Hiromichi Kawaida ₁ , Daisuke Ichikawa ₁

Affiliation

Background

Cancer-associated fibroblasts exhibit diversity and have several subtypes. The underlying relationship between the diversity of cancer-associated fibroblasts and their effect on gastric cancer progression remains unclear. In this study, mesenchymal stem cells were differentiated into cancer-associated fibroblasts with gastric cancer cell lines; clinical specimens were used to further investigate the impact of cancer-associated fibroblast diversity on cancer progression.

Methods

Nine gastric cancer cell lines (NUGC3, NUGC4, MKN7, MKN45, MKN74, FU97, OCUM1, NCI-N87, and KATOIII) were used to induce mesenchymal stem cell differentiation into cancer-associated fibroblasts. The cancer-associated fibroblasts were classified based on ACTA2 and PDPN expression. Cell function analysis was used to examine the impact of cancer-associated fibroblast subtypes on cancer cell phenotype. Tissue samples from 97gastric patients who underwent gastrectomy were used to examine the clinical significance of each subtype classified according to cancer-associated fibroblast expression.

Results

Co-culture of mesenchymal stem cells with nine gastric cancer cell lines revealed different subtypes of ACTA2 and PDPN expression in differentiated cancer-associated fibroblasts. Cancer-associated fibroblast subtypes with high ACTA2 plus PDPN expression levels significantly increased gastric cancer cell migration, invasion, and proliferation. The cancer-associated fibroblast subtype with ACTA2 plus PDPN expression was an independent prognostic factor along with lymph node metastasis for patients who had gastric cancer and were undergoing surgery.

Conclusions

Cancer-associated fibroblasts are educated by gastric cancer cells during the development of cancer-associated fibroblast diversity. Differentiated cancer-associated fibroblasts with distinct expression patterns could affect gastric cancer progression and enable prognostic stratification for gastric cancer.

中文翻译：

胃癌间质特征的预后影响

背景

癌症相关成纤维细胞表现出多样性并具有多种亚型。癌症相关成纤维细胞的多样性与其对胃癌进展的影响之间的潜在关系仍不清楚。在这项研究中，间充质干细胞与胃癌细胞系一起分化为癌症相关成纤维细胞；临床标本用于进一步研究癌症相关成纤维细胞多样性对癌症进展的影响。

方法

使用九种胃癌细胞系（NUGC3、NUGC4、MKN7、MKN45、MKN74、FU97、OCUM1、NCI-N87 和 KATOIII）诱导间充质干细胞分化为癌症相关成纤维细胞。根据ACTA2和PDPN表达对癌症相关成纤维细胞进行分类。细胞功能分析用于检查癌症相关成纤维细胞亚型对癌细胞表型的影响。使用来自 97 名接受胃切除术的胃患者的组织样本来检查根据癌症相关成纤维细胞表达分类的每种亚型的临床意义。

结果

间充质干细胞与九种胃癌细胞系的共培养揭示了分化的癌症相关成纤维细胞中ACTA2和PDPN表达的不同亚型。具有高ACTA2加PDPN表达水平的癌症相关成纤维细胞亚型显着增加胃癌细胞迁移、侵袭和增殖。对于患有胃癌并接受手术的患者来说，具有 ACTA2 加 PDPN 表达的癌症相关成纤维细胞亚型与淋巴结转移一起是一个独立的预后因素。