Molecular profile of poorly cohesive gastric carcinoma with special reference to survival

Koseki, Yusuke; Hatakeyama, Keiichi; Terashima, Masanori; Nagashima, Takeshi; Urakami, Kenichi; Ohshima, Keiichi; Aizawa, Daisuke; Sugino, Takashi; Furukawa, Katsunori; Fujiya, Keiichi; Tanizawa, Yutaka; Bando, Etsuro; Okamura, Yukiyasu; Akiyama, Yasuto; Yamaguchi, Ken

doi:10.1007/s10120-023-01390-5

Cited by 6 publications

(1 citation statement)

References 33 publications

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“…As a highly phenotypically and molecularly heterogeneous disease, the intra-tumor heterogeneity of GC is a major obstacle to precision therapy [ 60 , 61 ]. PCC is a distinct histological subtype of GC that tends to metastasize and often results in low survival [ 62 ]. Currently, immunotherapy targeting the PD-1/PDL1 pathway is one of the most effective therapeutic options, but its efficacy in PCC is unsatisfactory, partly due to the highly immunosuppressive state of PCC [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

IFIT1 + neutrophil is a causative factor of immunosuppressive features of poorly cohesive carcinoma (PCC)

Liu,

Li,

Han

et al. 2024

J Transl Med

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The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.

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Section: Discussionmentioning

confidence: 99%

IFIT1 + neutrophil is a causative factor of immunosuppressive features of poorly cohesive carcinoma (PCC)

Liu,

Li,

Han

et al. 2024

J Transl Med

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Diagnostic value of dual-source, dual-energy computed tomography combined with the neutrophil-lymphocyte ratio for discriminating gastric signet ring cell from mixed signet ring cell and non-signet ring cell carcinomas

Song,

Wang,

Zhu

et al. 2024

Abdom Radiol

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Purpose To explore the diagnostic value of dual-source computed tomography (DSCT) and neutrophil to lymphocyte ratio (NLR) for differentiating gastric signet ring cell carcinoma (SRC) from mixed SRC (mSRC) and non-SRC (nSRC). Methods This retrospective study included patients with gastric adenocarcinoma who underwent DSCT between August 2019 and June 2021 at our Hospital. The iodine concentration in the venous phase (ICvp), standardized iodine concentration (NICVP), and the slope of the energy spectrum curve (kVP) were extracted from DSCT data. NLR was determined from laboratory results. DSCT (including ICVP, NICVP, and kVP) and combination (including DSCT model and NLR) models were established based on the multinomial logistic regression analysis. The receiver operator characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic value. Results A total of 155 patients (SRC [n = 45, aged 61.22 ± 11.4 years], mSRC [n = 60, aged 61.09 ± 12.7 years], and nSRC [n = 50, aged 67.66 ± 8.76 years]) were included. There were significant differences in NLR, ICVP, NICVP, and kVP among the SRC, mSRC, and nSRC groups (all P < 0.001). The AUC of the combination model for SRC vs. mSRC + nSRC was 0.964 (95% CI: 0.923-1.000), with a sensitivity of 98.3% and a specificity of 86.7%, higher than with DSCT (AUC: 0.959, 95% CI: 0.919–0.998, sensitivity: 90.0%, specificity: 89.9%) or NLR (AUC: 0.670, 95% CI: 0.577–0.768, sensitivity: 62.2%, specificity: 61.8%). Conclusion DSCT combined with NLR showed high diagnostic efficacy in differentiating SRC from mSRC and nSRC.

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Macroscopic type is implicated in the prognostic impact of initial chemotherapy on peritoneal lavage cytology-positive gastric cancer with no other noncurative factors

Kano,

Ichikawa,

Aizawa

et al. 2024

Int J Clin Oncol

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BackgroundInitial chemotherapy (Initial-C) followed by surgery is a promising treatment strategy for peritoneal lavage cytology-positive gastric cancer (CY1 GC) with no other noncurative factors. The aim of this study was to investigate the survival advantage of Initial-C compared to initial surgery (Initial-S) for this disease according to the macroscopic type, which was associated with prognosis and the e cacy of chemotherapy in GC. MethodsOne hundred eighty-nine patients who were diagnosed with CY1 GC with no other noncurative factors at four institutions from January 2007 to December 2018 were enrolled. The patients were divided into a macroscopic type 4 group (N = 48) and a non-type 4 group (N = 141). The in uence of initial treatment on overall survival (OS) in each group was evaluated. ResultsIn the type 4 group, the 5-year OS rates of Initial-C (N = 35) and Initial-S (N = 13) were 11.6% and 0%, respectively (P = 0.801). The multivariate analysis could not show the survival advantage of Initial-C. In the non-type 4 group, the 5-year OS rates of Initial-C (N = 41) and Initial-S (N = 100) were 48.4% and 29.0%, respectively (P = 0.020). The multivariate analysis revealed that Initial-C was independently associated with prolonged OS (hazard ratio, 0.591; 95% con dence interval, 0.375-0.933: P = 0.023). ConclusionsInitial-C improves the prognosis of non-type 4 CY1 GC with no other noncurative factors. On the other hand, further development of effective chemotherapeutic regimens and innovative treatment strategies are required for type 4 CY1 GC.

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Molecular profile of poorly cohesive gastric carcinoma with special reference to survival

Cited by 6 publications

References 33 publications

IFIT1 + neutrophil is a causative factor of immunosuppressive features of poorly cohesive carcinoma (PCC)

IFIT1 + neutrophil is a causative factor of immunosuppressive features of poorly cohesive carcinoma (PCC)

Diagnostic value of dual-source, dual-energy computed tomography combined with the neutrophil-lymphocyte ratio for discriminating gastric signet ring cell from mixed signet ring cell and non-signet ring cell carcinomas

Macroscopic type is implicated in the prognostic impact of initial chemotherapy on peritoneal lavage cytology-positive gastric cancer with no other noncurative factors

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