Sarkar Joy, Oshi Masanori, Satyananda Vikas, Chida Kohei, Yan Li, Maiti Aparna, Hait Nitai, Endo Itaru, Takabe Kazuaki
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
These authors contributed equally to this work.
World J Oncol. 2024 Apr;15(2):181-191. doi: 10.14740/wjon1732. Epub 2024 Mar 21.
Spinster homologue 2 (SPNS2) is a transporter of sphingosine-1-phosphate (S1P), a bioactive lipid linked to cancer progression. We studied the link between gene expression, tumor aggressiveness, and outcomes in patients with hepatocellular carcinoma (HCC).
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).
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).
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 effects.
Spinster同源物2（SPNS2）是1-磷酸鞘氨醇（S1P）的转运蛋白，S1P是一种与癌症进展相关的生物活性脂质。我们研究了肝细胞癌（HCC）患者基因表达、肿瘤侵袭性和预后之间的联系。
分析癌症基因组图谱（TCGA）（n = 350）中HCC患者的基因表达情况，并将GSE76427（n = 115）作为验证队列，同时分析肝组织队列GSE6764（n = 75）。
高SPNS2水平的HCC与高水平的淋巴管生成相关因子显著相关。正常肝脏和早期HCC中SPNS2表达明显高于晚期HCC（P < 0.02）。高SPNS2水平富集了免疫反应相关基因集；炎症、干扰素（IFN）-α、IFN-γ反应以及肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6/Janus激酶/信号转导子和转录激活子（JAK/STAT3）信号传导、补体和同种异体移植排斥反应，但未显著浸润特定免疫细胞或细胞溶解活性评分。高SPNS2水平的HCC富集了肿瘤加重途径基因集，如KRAS（ Kirsten大鼠肉瘤病毒）信号传导，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呈负相关。此外，高SPNS2水平的HCC基质细胞浸润显著增加，表明低SPNS2水平的HCC具有高增殖性。最后，高SPNS2水平的HCC与更好的无病生存期、疾病特异性生存期和总生存期相关（分别为P = 0.031、0.046和0.040）。
尽管SPNS2表达与淋巴管生成和其他促癌途径相关，但它也富集了免疫反应。与HCC相比，正常肝脏中SPNS2水平更高，且与癌细胞增殖呈负相关，生存期更好。尽管存在有害影响，但SPNS2表达可能对HCC患者有益。
