High <italic style="font-style: italic">SLC35C2 </italic>expression promotes proliferation and migration of hepatocellular carcinoma and is associated with immune infiltration and drug sensitivity:<italic style="font-style: italic"> </italic>an analysis based on multi-omics database and <italic style="font-style: italic">in vitro</italic> functional verification

Zhou Fangjun; Yang Jiani; Zhang Liangjun; Chai Jin

doi:10.16016/j.2097-0927.202605003

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High SLC35C2 expression promotes proliferation and migration of hepatocellular carcinoma and is associated with immune infiltration and drug sensitivity: an analysis based on multi-omics database and in vitro functional verification

Basic Medicine | 更新时间：2026-09-16

- High SLC35C2 expression promotes proliferation and migration of hepatocellular carcinoma and is associated with immune infiltration and drug sensitivity: an analysis based on multi-omics database and in vitro functional verification
- Journal of Army Medical University Vol. 48, Issue 17, Pages: 2506-2516(2026)
- 作者机构：
  
  陆军军医大学（第三军医大学）第一附属医院消化内科，重庆
- 作者简介：
  
  Zhang Liangjun，E-mail： liangjun.zhang@cldcsw.org
  Chai Jin，E-mail：jin. chai@cldcsw.org
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82470668);the Project for New Chongqing Young Innovative Talents(CSTB2025YITP-QCRCX0099);the General Project of Natural Science Foundation of Chongqing(CSTB2023NSCQ-MSX0623)
- DOI：10.16016/j.2097-0927.202605003
  CLC： R394.3;R730.23;R735.7
- Received：06 May 2026，
  
  Revised：2026-07-15，
  
  Accepted：19 July 2026，
  
  Published：15 September 2026
- 稿件说明：
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周方军，杨佳妮，张樑君，等.SLC35C2高表达促进肝细胞癌增殖迁移且与免疫浸润及药物敏感性相关：基于多组学数据库分析及体外功能验证［J］.陆军军医大学学报，2026，48（17）：2506-2516.DOI：10.16016/j.2097-0927.202605003.

Zhou F J，Yang J N，Zhang L J，et al.High SLC35C2 expression promotes proliferation and migration of hepatocellular carcinoma and is associated with immune infiltration and drug sensitivity： an analyses based on multi-omics database and in vitro functional verification［J］.J Army Med Univ，2026，48（17）：2506-2516.DOI：10.16016/j.2097-0927.202605003.
周方军，杨佳妮，张樑君，等.SLC35C2高表达促进肝细胞癌增殖迁移且与免疫浸润及药物敏感性相关：基于多组学数据库分析及体外功能验证［J］.陆军军医大学学报，2026，48（17）：2506-2516.DOI：10.16016/j.2097-0927.202605003. DOI：

Zhou F J，Yang J N，Zhang L J，et al.High SLC35C2 expression promotes proliferation and migration of hepatocellular carcinoma and is associated with immune infiltration and drug sensitivity： an analyses based on multi-omics database and in vitro functional verification［J］.J Army Med Univ，2026，48（17）：2506-2516.DOI：10.16016/j.2097-0927.202605003. DOI：

摘要

目的

肝细胞癌（hepatocellular carcinoma，HCC）病情复杂，预后难测，识别特异性标志物，有助于临床更好地了解HCC的发生发展机制，进一步改善HCC的诊治和预后评估。本研究基于多个数据库系统评估溶质载体蛋白家族35成员C2（solute carrier family 35 member c2，

SLC35C2

）在HCC的表达模式、预后相关性、免疫浸润相关性。

方法

整合TCGA、GTEx、GEO、HPA、CellMiner、TCIA等多组学数据库，评估

SLC35C2

的临床价值，并构建HCC风险预测列线图。通过多元回归分析，识别HCC患者（

=373）总体生存相关临床特征的单变量和多变量；通过GO功能、KEGG通路富集和基因集富集分析（gene set enrichment analysis，GSEA）探索其潜在功能通路；利用ESTIMATE计算肿瘤微环境评分，包括基质评分、免疫评分和ESTIMATE评分，利用CIBERSORT评估肿瘤浸润免疫细胞的相对丰度；通过TCIA与CellMiner评估其对免疫治疗响应及药物敏感性的预测价值；在过表达

SLC35C2

的人肝癌细胞（human hepatocellular carcinoma cells G2，HepG2）中分别使用细胞计数盒-8（cell counting kit-8，CCK-8）法、Transwell法、划痕实验检测其对细胞增殖与迁移的影响。

结果

SLC35C2

在HCC中表达升高（

0.05），提示患者预后不良；基于TCGA数据的多因素Cox回归分析表明，

SLC35C2

高表达是HCC患者预后的独立危险因素（

0.05）。功能富集分析表明，

SLC35C2

与细胞周期、DNA复制和Wnt信号通路等生物学过程密切相关（

0.05）。免疫相关性分析显示，在HCC组织中，

SLC35C2

高表达组的基质评分、免疫评分和ESTIMATE评分均显著低于低表达组（均

0.05），免疫表型评分与

SLC35C2

表达水平呈负相关（

0.05）。

SLC35C2

表达与抗肿瘤药物敏感性相关，且提示对免疫治疗的反应欠佳（

0.05），具体表现为

SLC35C2

高表达与达拉非尼（dabrafenib）、R-1530、LDK-378及甲氨蝶呤（methotrexate）的半数抑制浓度（half maximal inhibitory concentration，IC

）呈正相关（

0.05），与NU-6027、泊马度胺（pomalidomide）、I-BET-762及PT-2385的IC

呈负相关（

0.05）。体外实验表明，过表达

SLC35C2

可显著增强HepG2细胞的增殖和迁移能力（

0.05）。

结论

SLC35C2

与HCC的异常免疫浸润有关，其高表达提示HCC患者的不良预后；过表达

SLC35C2

能够促进HCC细胞系的迁移和侵袭，提示

SLC35C2

可作为HCC疾病管理和干预的潜在生物标志物和靶点。

Abstract

Objective

Hepatocellular carcinoma(HCC) is a complex disease with unpredictable prognosis. Identifying specific biomarkers can facilitate a better understanding of the pathogenesis of HCC and further improve its diagnosis

treatment

and prognostic assessment. This study aims to investigate the expression pattern

prognostic relevance

and immune infiltration correlation of solute carrier family 35 member C2(

SLC35C2

) in HCC based on multiple databases.

Methods

Multi-omics databases including TCGA

GTEx

GEO

HPA

CellMiner

and TCIA were integrated to assess the clinical value of

SLC35C2

and an HCC risk prediction nomogram was constructed. Univariate and multivariate analyses were performed to identify clinical characteristics associated with overall survival in HCC patients(

=373). GO functional annotation

KEGG pathway enrichment

and gene set enrichment analysis(GSEA) were conducted to explore potential functional pathways. ESTIMATE was used to calculate tumor microenvironment scores

including stromal score

immune score and

ESTIMATE score

and CIBERSORT was employed to evaluate the relative abundance of tumor-infiltrating immune cells. The predictive value of SLC35C2 for immunotherapy response and drug sensitivity was assessed through TCIA and CellMiner. CCK-8

Transwell and wound healing assays were applied to determine the effects of

SLC35C2

overexpression on the cell proliferation and migration in human HCC cell line HepG2.

Results

SLC35C2

was highly expressed in HCC(

0.05)

suggesting poor prognosis for patients. Multivariate Cox regression analysis on TCGA data indicated that high

SLC35C2

expression was an independent risk factor for prognosis in HCC patients(

0.05). Functional enrichment analyses indicated that

SLC35C2

was closely associated with biological processes such as cell cycle

DNA replication

and Wnt signaling pathway(

0.05). Immune-related analysis showed that in HCC tissues

the stromal score

immune score

and ESTIMATE score were significantly lower in the high-expression group of

SLC35C2

than the low-expression group(all

0.05). The immunophenotype score was negatively correlated with

SLC35C2

expression level(

0.05).

SLC35C2

expression was associated with antitumor drug sensitivity

and its high expression indicated poor response to immunotherapy(

0.05). Specifically

high

SLC35C2

expression was positively correlated with the half-maximal inhibitory concentration (IC

) of dabrafenib

R-1530

LDK-378

and methotrexate(

0.05)

and negatively correlated with the IC

of NU-6027

pomalidomide

I-BET-762

and PT-2385(

0.05). In vitro experiments demonstrated that overexpression of

SLC35C2

significantly enhanced the proliferation and migration of He

pG2(

0.05).

Conclusion

SLC35C2

is associated with abnormal immune infiltration in HCC

and its high expression indicates poor prognosis for HCC patients. Overexpression of

SLC35C2

can enharce the migration and invasion of HCC cell line

suggesting that

SLC35C2

may serve as a potential biomarker and target for the management and intervention of HCC.

关键词

Keywords

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High SLC35C2 expression promotes proliferation and migration of hepatocellular carcinoma and is associated with immune infiltration and drug sensitivity: an analysis based on multi-omics database and in vitro functional verification

DOI：10.16016/j.2097-0927.202605003

摘要

Abstract

关键词

Keywords

references