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Gastric tubular adenocarcinoma with diffuse neutrophils infiltrating: characteristics and probable treatment strategy

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Abstract

Background

Gastric adenocarcinoma is a highly heterogeneous malignancy with varying prognoses. In clinicopathological practice, we noticed a special tubular adenocarcinoma with diffuse neutrophils infiltrating (TADNI). However, the proportion and characteristics of TADNI remain unclear. This study aimed to evaluate the features of TADNI and explore probable treatments.

Methods

We divided 289 tubular adenocarcinoma cases into the TADNI and non-TADNI (nTADNI) groups by histological neutrophil quantity and performed immunohistochemistry of treatment-associated markers (CXCR1, CXCR2, PD-L1, CD8, HER2 and VEGFR2). Then we evaluated the clinical and morphological features in these cases. We also compared the value of histological features and peripheral blood neutrophil test. In addition, multiomics bioinformatic analyses were performed using the public datasets.

Results

In our cohort, TADNI accounted for 10.4% of all tubular adenocarcinoma cases. These cases had worse prognoses (especially the neutrophils mainly outside the tubes) than nTADNI cases. The histological identification of TADNI had more prognostic value than peripheral blood neutrophils. CXCR1/CXCR2 expression was significantly high in TADNI group which indicated that CXCR1/CXCR2 inhibitors might be beneficial for TADNI patients. There were no significant differences in the expression of PD-L1, CD8, HER2 and VEGFR2. The analyses of TCGA data confirmed that TADNI cases had poorer prognoses and higher CXCR1/CXCR2 expression. Bioinformatic results also revealed molecular features (more hsa-mir-223 expression, fewer CD8-positive T cells and regulatory T cells, tighter communication between tumor cells’ CXCR1/CXCR2 and neutrophils’ CXCL5/CXCL8) of this type.

Conclusions

TADNI is a special morphological subtype with poorer prognoses and unique molecular characteristics, which might benefit from CXCR1/CXCR2 inhibitors.

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Availability of data and material

Available. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the CAMS Innovation Fund for Medical Sciences (CIFMS) (Grant No. 2021-I2M-1-067) and the Beijing Hope Run Special Fund (No. LC2021A20 and No. LC2021B16).

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Author notes

  1. Bingzhi Wang and Yongjian Zhu contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Bingzhi Wang, Zhuo Li, Long Wang, Wei Rao, Na Cheng, Rongshan Chen, Jianming Ying & Liyan Xue

  2. Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Yongjian Zhu

  3. Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Shaoming Wang

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  1. Bingzhi Wang
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Contributions

LX performed the study concept and design; JY made the major revision for this manuscript; BW, YZ, ZL and WR performed the development of methodology and writing, review and revision of the paper; SW review the statistical methods in this research; NC and RC provided acquisition, analysis and interpretation of data, and statistical analysis; LW provided technical and material support. All authors read and approved the final paper.

Corresponding author

Correspondence to Liyan Xue.

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Ethical approval and consent to participate

Ethical approval was approved by the CICAMS ethics committee prior to commencing this study (No. 21/105-2776). All methods were carried out in accordance with relevant guidelines and regulations, and informed consent was obtained from all participants.

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Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1Supplementary Fig. 1. The flowchart of this study (PDF 294 KB) (PDF 293 kb)

10120_2023_1446_MOESM2_ESM.pdf

Supplementary file2Supplementary Fig. 2. The survival curves of outside pattern and other 2 patterns cases in TADNI group (PDF 24 kb)

Supplementary file3Supplementary Fig. 3. Additional IHC staining. Markers and clones were shown (PDF 1108 kb)

10120_2023_1446_MOESM4_ESM.pdf

Supplementary file4Supplementary Fig. 4. (a) Multiplex IHC sections show that CXCR1 co-located with AE1/AE3 while CXCL8 co-located with CD66b. (b) Spatial distance analyses show the distance between of CD8+ cells / CD66b+ cells and tumor cells (PDF 414 kb)

10120_2023_1446_MOESM5_ESM.xlsx

Supplementary file5Supplementary Table 1. Detailed information of TADNI cases in our research. Supplementary Table 2. Antibodies' information. Supplement Table 3. TCGA cases grouping by TADNI vs nTADNI. Supplement Table 4. Nanostring RNA expression results. Supplement Table 5. Neutrophils percentage for each tumor samples in GSM7446522 dataset. Supplement Table 6. Spatial analyses results in five recent TADNI cases (XLSX 24 kb)

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Wang, B., Zhu, Y., Wang, S. et al. Gastric tubular adenocarcinoma with diffuse neutrophils infiltrating: characteristics and probable treatment strategy. Gastric Cancer 27, 86–101 (2024). https://doi.org/10.1007/s10120-023-01446-6

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