Spinster Homologue 2 Expression Correlates With Improved Patient Survival in Hepatocellular Carcinoma Despite Association With Lymph-Angiogenesis.

IF 2.1 Q3 ONCOLOGY

World Journal of Oncology Pub Date : 2024-04-01 Epub Date: 2024-03-21 DOI:10.14740/wjon1732

Joy Sarkar, Masanori Oshi, Vikas Satyananda, Kohei Chida, Li Yan, Aparna Maiti, Nitai Hait, Itaru Endo, Kazuaki Takabe

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引用次数: 0

Abstract

Background: Spinster homologue 2 (SPNS2) is a transporter of sphingosine-1-phosphate (S1P), a bioactive lipid linked to cancer progression. We studied the link between SPNS2 gene expression, tumor aggressiveness, and outcomes in patients with hepatocellular carcinoma (HCC).

Methods: Gene expression in patients with HCC was analyzed from the Cancer Genome Atlas (TCGA) (n = 350) and GSE76427 (n = 115) as a validation cohort, as well as liver tissue cohort GSE6764 (n = 75).

Results: High-SPNS2 HCC was significantly associated with high level of lymph-angiogenesis-related factors. SPNS2 expression was significantly higher in normal liver and early HCC versus advanced HCC (P < 0.02). High SPNS2 levels enriched immune response-related gene sets; inflammatory, interferon (IFN)-α, IFN-γ responses, and tumor necrosis factor (TNF)-α, interleukin (IL)-6/Janus kinase/signal transducer and activator of transcription (JAK/STAT3) signaling, complement and allograft rejection, but did not significantly infiltrate specific immune cells nor cytolytic activity score. High-SPNS2 HCC enriched tumor aggravating pathway gene sets such as KRAS (Kirsten rat sarcoma virus) signaling, but inversely correlated with Nottingham histological grade, MKI67 (marker of proliferation Ki-67) expression, and cell proliferation-related gene sets. Further, high-SPNS2 HCC had significantly high infiltration of stromal cells, showing that low-SPNS2 HCC is highly proliferative. Finally, high-SPNS2 HCC was associated with better disease-free, disease-specific, and overall survival (P = 0.031, 0.046, and 0.040, respectively).

Conclusions: Although SPNS2 expression correlated with lymph-angiogenesis and other cancer-promoting pathways, it also enriched immune response. SPNS2 levels were higher in normal liver compared to HCC, and inversely correlated with cancer cell proliferation and better survival. SPNS2 expression may be beneficial in HCC patients despite detrimental in-vitro effects.

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Spinster Homologue 2 的表达与肝细胞癌患者生存率的提高有关，尽管它与淋巴-血管生成有关。

背景：鞘氨醇同源物 2（SPNS2）是鞘氨醇-1-磷酸（S1P）的转运体，S1P是一种与癌症进展相关的生物活性脂质。我们研究了 SPNS2 基因表达、肿瘤侵袭性和肝细胞癌（HCC）患者预后之间的联系：分析了癌症基因组图谱（TCGA）（n = 350）和作为验证队列的 GSE76427（n = 115）以及肝组织队列 GSE6764（n = 75）中 HCC 患者的基因表达：结果：高SPNS2 HCC与高水平的淋巴-血管生成相关因子显著相关。正常肝脏和早期 HCC 中 SPNS2 的表达明显高于晚期 HCC（P < 0.02）。高水平的SPNS2富集了免疫反应相关基因集；炎症、干扰素（IFN）-α、IFN-γ反应、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6/破伤风激酶/信号转导和转录激活因子（JAK/STAT3）信号转导、补体和异体移植排斥反应，但对特异性免疫细胞的浸润和细胞溶解活性评分无明显影响。高SPNS2 HCC富集了肿瘤恶化通路基因集，如KRAS（Kirsten大鼠肉瘤病毒）信号转导，但与诺丁汉组织学分级、MKI67（增殖标志物Ki-67）表达和细胞增殖相关基因集成反比。此外，高SPNS2 HCC的基质细胞浸润明显较高，这表明低SPNS2 HCC具有高度增殖性。最后，高SPNS2 HCC与较好的无病生存率、疾病特异性生存率和总生存率相关（P = 0.031、0.046 和 0.040）：结论：尽管SPNS2的表达与淋巴管生成和其他促癌通路相关，但它也丰富了免疫反应。与 HCC 相比，SPNS2 在正常肝脏中的水平更高，并且与癌细胞增殖和更好的生存率成反比。尽管SPNS2的表达对体外实验有不利影响，但它可能对HCC患者有益。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Journal of Oncology ONCOLOGY-

CiteScore

6.10

自引率

15.40%

发文量

期刊介绍： World Journal of Oncology, bimonthly, publishes original contributions describing basic research and clinical investigation of cancer, on the cellular, molecular, prevention, diagnosis, therapy and prognosis aspects. The submissions can be basic research or clinical investigation oriented. This journal welcomes those submissions focused on the clinical trials of new treatment modalities for cancer, and those submissions focused on molecular or cellular research of the oncology pathogenesis. Case reports submitted for consideration of publication should explore either a novel genomic event/description or a new safety signal from an oncolytic agent. The areas of interested manuscripts are these disciplines: tumor immunology and immunotherapy; cancer molecular pharmacology and chemotherapy; drug sensitivity and resistance; cancer epidemiology; clinical trials; cancer pathology; radiobiology and radiation oncology; solid tumor oncology; hematological malignancies; surgical oncology; pediatric oncology; molecular oncology and cancer genes; gene therapy; cancer endocrinology; cancer metastasis; prevention and diagnosis of cancer; other cancer related subjects. The types of manuscripts accepted are original article, review, editorial, short communication, case report, letter to the editor, book review.