泛癌分析SERINC2作为肿瘤预后和免疫生物标志物的潜力

doi:10.16288/j.yczz.25-090

遗传 ›› 2026, Vol. 48 ›› Issue (3): 287-300.doi: 10.16288/j.yczz.25-090

泛癌分析SERINC2作为肿瘤预后和免疫生物标志物的潜力

赵敏¹(), 应慧琪¹^,², 杨益雷¹, 陈青绿¹, 林文¹^,², 蔡振寨¹, 林李淼¹, 滕洋洋¹()

1.温州医科大学附属第二医院育英儿童医院，温州 325000
2.温州医科大学第二临床医学院，温州 325000

收稿日期:2025-06-26 修回日期:2025-09-26 出版日期:2025-10-27 发布日期:2025-10-17
通讯作者: 滕洋洋，硕士，研究员，研究方向：消化内科。E-mail: 221034@wzhealth.com
作者简介:赵敏，硕士研究生，专业方向：消化内科。E-mail: 572843113@qq.com
基金资助:
温州市科技局项目(Y2023228);浙江省基础公益研究计划(LGF21H160035)

Potential of SERINC2 as a biomarker in tumor prognosis and immunology: analysis from pan-cancer studies

Min Zhao¹(), Huiqi Ying¹^,², Yilei Yang¹, Qinglv Chen¹, Wen Lin¹^,², Zhenzhai Cai¹, Limiao Lin¹, Yangyang Teng¹()

1. The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
2. The Second Clinical Medical College of Wenzhou Medical University, Wenzhou 325000, China

Received:2025-06-26 Revised:2025-09-26 Published:2025-10-27 Online:2025-10-17
Supported by:
Wenzhou Science and Technology Bureau Project(Y2023228);Zhejiang Provincial Basic Public Welfare Research Program(LGF21H160035)

摘要/Abstract

摘要：

丝氨酸整合因子(serine incorporator，SERINC)是一种与脂质合成有关的跨膜蛋白，其中SERINC2与癌症发生进展中的多种生物学过程相关。胰腺癌(pancreatic adenocarcinoma，PAAD)作为一种高度恶性的肿瘤，预后极差且缺乏有效的生物标志物，目前尚无文献报道SERINC2与泛癌及肿瘤免疫的关系。因此，基于SERINC2预测PAAD的预后，可为开发以SERINC2为核心的肿瘤诊断标志物及免疫治疗策略奠定基础。本研究基于癌症基因组图谱(The Cancer Genome Atlas，TCGA)、基因型-组织表达(Genotype-Tissue Expression，GTEx)和人类蛋白图谱(Human Protein Atlas，HPA)数据库中SERINC2在正常和肿瘤组织中的表达水平数据，证实SERINC2在多种癌症中异常高表达，且与临床病理分期显著相关(P<0.05)。通过基因组稳定性相关癌症分析(Genomic Stability Associated Cancer Analysis，GSCA)数据库分析拷贝数变异和甲基化对SERINC2表达的影响，发现拷贝数变异与SERINC2表达呈正相关，而甲基化水平则呈负相关(P<0.05)。使用TCGA数据库进一步分析SERINC2表达水平与免疫细胞浸润和肿瘤微环境评分的相关性，发现SERINC2表达与免疫检查点基因、免疫治疗、免疫浸润显著相关，并与肿瘤微环境评分在多数癌种中负相关(P<0.05)。使用“limma”包筛选出25个差异基因，构建的PAAD预后模型可有效区分高危/低危患者的生存预后。通过54例PAAD患者的免疫组化(immunohistochemical，IHC)验证SERINC2高表达与PAAD不良预后显著相关(中位总体生存期：19.67 vs 50.52个月，P=0.029)。上述结果表明，本研究为开发以SERINC2为核心的肿瘤诊断标志物及免疫治疗策略奠定了基础。

关键词: 丝氨酸整合因子2, 癌症预后, 免疫生物标志物, 泛癌分析, 拷贝数差异

Abstract:

Serine incorporator (SERINC) is a family of transmembrane protein involved in lipid synthesis. Among its family members, SERINC2 has been implicated in tumor pathogenesis. Pancreatic carcinoma (PAAD), a highly malignant tumor characterized by an extremely poor prognosis, lacks effective biomarkers. To date, the association between SERINC2 and pan-cancer or tumor immunity remains unreported in the literature. Consequently, investigating the utility of SERINC2 for prognostic prediction in PAAD lays the groundwork for developing diagnostic biomarkers and SERINC2-targeted immunotherapy strategies. In this study, we used the transcriptional data in normal and tumor tissues from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Human Protein Atlas (HPA). Analysis of publicly available data (TCGA, GTEx, HPA) revealed significant SERINC2 overexpression in multiple cancers, which was associated with advanced clinicopathological stage (P<0.05). Analysis of the Genomic Stability Associated Cancer Analysis (GSCA) database revealed a significant positive correlation between copy number variation (CNV) and SERINC2 expression levels. Conversely, DNA methylation was inversely correlated with SERINC2 expression (P<0.05). Further investigation utilizing TCGA database demonstrated that SERINC2 expression was significantly associated with the expression of immune checkpoint molecules, response to immunotherapy, and the extent of immune cell infiltration. Notably, a negative correlation was observed between SERINC2 expression and the tumor microenvironment (TME) score in most cancer types analyzed (P<0.05). We constructed a prognostic model for PAAD based on 25 differentially expressed genes (DEGs) identified from the TCGA cohort using the “limma” package. This model effectively stratified patients into high- and low-risk groups with significantly distinct survival outcomes. Immunohistochemical (IHC) analysis of 54 PAAD patient samples validated that high SERINC2 expression was significantly associated with poorer prognosis; patients with high expression had a significantly shorter median overall survival (19.67 vs 50.52 months, P=0.029). Collectively, our findings provide a rationale for developing SERINC2-based diagnostic biomarkers and immunotherapeutic strategies.

Key words: SERINC2, cancer prognosis, immunological biomarker, pan-cancer analysis, copy number variation

赵敏, 应慧琪, 杨益雷, 陈青绿, 林文, 蔡振寨, 林李淼, 滕洋洋. 泛癌分析SERINC2作为肿瘤预后和免疫生物标志物的潜力[J]. 遗传, 2026, 48(3): 287-300.

Min Zhao, Huiqi Ying, Yilei Yang, Qinglv Chen, Wen Lin, Zhenzhai Cai, Limiao Lin, Yangyang Teng. Potential of SERINC2 as a biomarker in tumor prognosis and immunology: analysis from pan-cancer studies[J]. Hereditas(Beijing), 2026, 48(3): 287-300.

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图2

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图5

附表1

基于相关性分析鉴定泛癌细胞SERINC2相关基因"

基因	数量	Avercor	阳性	阴性
PLEKHN1	28	0.349960538627953	28	0
PERM1	24	0.315735112568226	24	0
AGRN	25	0.38074728115349	25	0
RNF223	22	0.332760082126328	21	1
SDF4	28	0.343290671922464	28	0
CPTP	29	0.396762409417379	29	0
DVL1	23	0.340216489419806	23	0
VWA1	21	0.316683799334954	21	0
PRKCZ	27	0.327940235268636	26	1
RER1	25	0.328772243849531	25	0
ARHGEF16	25	0.378395439929186	25	0
TPRG1L	21	0.315984984067857	21	0
CLSTN1	21	0.306551079325536	20	1
PEX14	24	0.326543788868636	24	0
AGTRAP	22	0.350591655758513	22	0
KIAA2013	26	0.317332030228793	26	0
PLOD1	21	0.327382964836107	21	0
DHRS3	18	0.333882844592026	18	0
TMEM51	20	0.32879480958882	19	1
FBLIM1	24	0.32759120726393	23	1
EPHA2	23	0.311198269226665	22	1
ARHGEF10L	21	0.309965871049903	20	1
PQLC2	25	0.351606958976778	25	0
CAPZB	24	0.305059159423125	24	0
CAMK2N1	23	0.310287736927153	21	2
MUL1	25	0.320708853233717	25	0
LYPLA2	28	0.39462297211551	28	0
GALE	29	0.399313974934316	29	0
HMGCL	24	0.305398337552395	24	0
PAFAH2	22	0.334387446550582	22	0
CNKSR1	21	0.330303254169143	19	2
SH3BGRL3	23	0.345097628658192	23	0
DHDDS	24	0.301913066953406	24	0
RPS6KA1	25	0.346273325300042	24	1
KDF1	25	0.371100225187239	25	0
SLC9A1	26	0.375765472131428	26	0
TMEM222	24	0.309315071833073	24	0
PTPRU	22	0.330965521251046	22	0
TINAGL1	22	0.429852800766259	21	1
PEF1	24	0.359775203689673	24	0
KIAA1522	26	0.383806999962195	26	0
TMEM54	24	0.350910314081146	24	0
PHC2	24	0.321854199118675	24	0
GJB3	20	0.32625700394145	19	1
KIAA0319L	22	0.309822178918176	22	0
ADPRHL2	22	0.305041766556224	22	0
RHBDL2	17	0.331719505119004	17	0
CAP1	21	0.306880029806984	21	0
C1orf210	21	0.307090476585564	20	1
ELOVL1	24	0.348494228497637	24	0
TMEM53	26	0.329968244346053	26	0
HECTD3	23	0.359358923546831	23	0
TSPAN1	27	0.322353643943738	26	1
CC2D1B	22	0.307281216287033	22	0
YIPF1	25	0.304501787905631	24	1
TMEM59	23	0.302111210871962	23	0
TTC22	19	0.305717438911571	18	1
TACSTD2	21	0.34084228673783	21	0
SLC44A3	22	0.312735808914853	21	1
RHOC	24	0.338222693214899	24	0
S100A10	17	0.309386420103174	17	0
S100A11	27	0.338973067598293	27	0
S100A16	19	0.336338897239388	19	0
S100A14	17	0.30013767258523	16	1
LMNA	19	0.31188815012727	18	1
PVRL4	19	0.302624648868545	19	0
LAMC2	21	0.329066733052498	20	1
C1orf106	21	0.30996154930184	19	2
LAD1	22	0.313856602346958	21	1
C1orf116	19	0.341212016769793	19	0
LAMB3	21	0.354590798512206	21	0
CAPN2	22	0.307979366774153	21	1
SDC1	25	0.358723573096413	25	0
EVA1A	17	0.306438714705796	17	0
PROM2	21	0.318101260903181	20	1
ITGB6	20	0.310466270861468	20	0
TMBIM1	22	0.317167487245507	22	0
CHPF	25	0.323239815293619	25	0
RNPEPL1	26	0.324022135199072	26	0
CDCP1	23	0.300217820449704	23	0
ALS2CL	20	0.322643033981362	19	1
SHISA5	17	0.300270214729214	17	0
LIPH	19	0.308066505481862	19	0
PPIC	22	0.310980852514011	22	0
PCDH1	18	0.309436581834779	18	0
MGAT4B	25	0.313520451714193	25	0
PPARD	23	0.316731357855882	23	0
TMEM63B	24	0.306249253434983	24	0
ADGRF4	17	0.326418922778946	17	0
PERP	20	0.317438504698287	20	0
ULBP2	19	0.310040292703203	18	1
MICALL2	22	0.300831627877244	22	0
ASL	24	0.302667008753105	24	0
MOSPD3	19	0.301124634282405	18	1
GNB2	23	0.326684449974956	23	0
CLDN23	17	0.305461123917443	17	0
PLEC	21	0.303792730207001	21	0
FAM129B	28	0.350024749633235	28	0
ZDHHC12	22	0.300085783796443	22	0
TOR4A	20	0.344002200493181	19	1
UBTD1	18	0.318906694971614	18	0
PKP3	23	0.319529458419933	23	0
EPS8L2	21	0.314591962197372	21	0
PNPLA2	25	0.304142290569298	25	0
CRACR2B	21	0.30081490046881	21	0
CD151	26	0.385927677294483	26	0
TOLLIP	24	0.304368805443615	23	1
PHLDA2	25	0.340971900145693	25	0
SLC35C1	24	0.328328408751407	24	0
RPS6KA4	19	0.32897694855372	19	0
CDC42BPG	23	0.322833531999689	22	1
CAPN1	26	0.37727374085526	26	0
CFL1	25	0.321729854916747	25	0
RAB1B	26	0.368890604956189	26	0
RIN1	21	0.335730536587498	21	0
RHOD	23	0.334950083668435	23	0
SSH3	21	0.335828564577149	20	1
CORO1B	26	0.320472178187892	26	0
UNC93B1	20	0.326847496224502	20	0
CTTN	21	0.305790746050287	21	0
ST14	28	0.33519977771397	28	0
LTBR	25	0.302386753617171	25	0
GPRC5A	20	0.322002118483461	20	0
VDR	19	0.31180194451812	19	0
KRT7	20	0.3221158990302	20	0
PXN	24	0.308290756837225	24	0
INF2	21	0.331240113777917	21	0
CEP170B	25	0.319545480455203	24	1
SPINT1	28	0.365025426592737	28	0
JMJD7	19	0.303683915385112	19	0
ANXA2	24	0.321357216420411	23	1
PKM	22	0.302123878190277	22	0
CD276	19	0.335749814521129	19	0
SNX33	25	0.30849879583022	25	0
SEMA4B	24	0.309630503608667	23	1
CIB1	23	0.313209936591992	23	0
RHBDF1	24	0.319479674074951	23	1
TMEM8A	30	0.339605647404895	30	0
RAB40C	22	0.32842759433115	22	0
PRSS22	24	0.322761084197868	22	2
TNFRSF12A	24	0.364341249784424	24	0
CCDC64B	23	0.383146204456197	23	0
PPL	21	0.344988763459547	21	0
PMM2	20	0.300334958586892	20	0
MVP	22	0.345207011714665	21	1
PRSS8	26	0.342991063828062	26	0
ADGRG1	22	0.333809426957589	22	0
USB1	26	0.34730302834318	26	0
MMP15	24	0.336969761298016	24	0
TRADD	20	0.30149995056839	20	0
NOL3	19	0.307191966604471	19	0
ELMO3	21	0.309741128256655	21	0
ATP6V0D1	22	0.335436118787227	21	1
ESRP2	21	0.324185805360763	21	0
CDH1	19	0.320470520992824	19	0
MARVELD3	24	0.343979736611352	24	0
BCAR1	28	0.361098327191817	27	1
TLDC1	20	0.325816252635604	20	0
CHMP1A	26	0.338368743608393	26	0
VPS9D1	23	0.302250886426353	23	0
TAX1BP3	25	0.311782993174585	25	0
TNK1	19	0.310324905993626	18	1
USP43	20	0.304653437067412	20	0
ERBB2	17	0.314977646590162	15	2
KRT19	20	0.318340720682333	19	1
GRN	23	0.305945325695862	23	0
PLCD3	23	0.300615882980187	21	2
ITGA3	24	0.332645835781796	23	1
TMEM92	19	0.318239073126564	19	0
P4HB	24	0.316229368466581	24	0
SLC16A3	22	0.318582747053056	21	1
MKNK2	20	0.308805194556244	20	0
TJP3	18	0.317088558853207	17	1
FUT3	17	0.340327760273573	17	0
SH2D3A	20	0.357199136075098	20	0
STXBP2	22	0.332052860735378	22	0
GIPC1	24	0.309392185428983	23	1
NR2F6	21	0.311905263454837	21	0
B3GNT3	22	0.340301179720172	22	0
CAPNS1	27	0.314543387078651	27	0
SPINT2	22	0.323154105935482	21	1
PPP1R37	20	0.310411891144451	20	0
PPP1R13L	23	0.345149736896881	23	0
KDELR1	27	0.319887143831549	27	0
TRPM4	19	0.361261212360656	19	0
PRRG2	25	0.313207040114647	23	2
TMC4	22	0.3371579906412	21	1
MBOAT7	26	0.306023064562392	26	0
EPS8L1	25	0.306987623816285	24	1
EPN1	25	0.3138398721545	25	0
CHMP2A	20	0.315104044224707	20	0
FAM110A	19	0.302218492898713	19	0
RRBP1	24	0.309232813510923	23	1
SDC4	21	0.315749213060936	21	0
PMEPA1	21	0.314643314521672	21	0
PPDPF	25	0.326104460318776	25	0
PTK6	21	0.335260859775456	19	2
PDXK	21	0.304736338084823	21	0
CSTB	19	0.335977827106967	19	0
SEC14L2	21	0.301493354246619	21	0
CARD10	22	0.331806352166629	22	0
WNT7B	21	0.312956711280954	20	1
PLXNB2	24	0.347941897311068	24	0

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分类	亚分类	ID	描述	基因比	背景比	P值	校正P值	q值	基因名称	数目
环境信息处理	信号分子和相互作用	hsa04512	细胞外基质-受体相互作用	4/16	89/8776	1.6389569893381e-05	0.000655582795735241	0.000500313186219	LAMC2/SDC1/LAMB3/SDC4	4
代谢	糖原合成和代谢	hsa00601	鞘糖脂生物合成—乳糖/新乳糖	2/16	28/8776	0.00114590513727669	0.0229181027455337	0.0174901310426442	FUT3/B3GNT3	2

基因	回归系数	HR	HR置信区间下限	HR置信区间上限	P值	95% CI	基因	回归系数	HR	HR置信区间下限	HR置信区间上限	P值	95% CI
VDR	0.48237283	1.6	0.5	5.3	0.42	(0.5~5.3)	CAP1	-2.122991686	0.12	0.035	0.41	0.00074	(0.035~0.41)
GPRC5A	0.400650772	1.5	0.74	3	0.27	(0.74~3)	B3GNT3	-0.014199198	0.99	0.43	2.3	0.97	(0.43~2.3)
LIPH	0.62411615	1.9	0.67	5.2	0.23	(0.67~5.2)	LAMC2	0.303749637	1.4	0.76	2.4	0.31	(0.76~2.4)
GJB3	-0.010745189	0.99	0.36	2.7	0.98	(0.36~2.7)	JMJD7	-4.394513566	0.012	1.70E-05	8.8	0.19	(1.7e-05~8.8)
CDCP1	0.369928694	1.4	0.43	4.8	0.55	(0.43~4.8)	GRN	0.226951942	1.3	0.56	2.8	0.58	(0.56~2.8)
EPHA2	0.354247286	1.4	0.61	3.3	0.41	(0.61~3.3)	KRT7	0.410349943	1.5	0.88	2.6	0.14	(0.88~2.6)
SLC16A3	0.055117261	1.1	0.44	2.5	0.9	(0.44~2.5)	PLEC	-0.160290696	0.85	0.38	1.9	0.69	(0.38~1.9)
PERP	-0.135948489	0.87	0.26	2.9	0.82	(0.26~2.9)	CAMK2N1	0.154702615	1.2	0.47	2.9	0.74	(0.47~2.9)
EPN1	-1.755155936	0.17	0.039	0.76	0.02	(0.039~0.76)	CSTB	-0.682032475	0.51	0.22	1.2	0.11	(0.22~1.2)
PCDH1	-0.20270329	0.82	0.21	3.1	0.77	(0.21~3.1)	PMEPA1	-0.615955147	0.54	0.25	1.2	0.12	(0.25~1.2)
PKM	0.404726591	1.5	0.71	3.2	0.29	(0.71~3.2)	KRT19	-0.242709798	0.78	0.37	1.7	0.53	(0.37~1.7)
S100A16	0.270199631	1.3	0.6	2.9	0.5	(0.6~2.9)	SH3BGRL3	-0.438332194	0.65	0.24	1.8	0.39	(0.24~1.8)
TMEM54	0.714964568	2	0.69	6	0.2	(0.69~6)

临床特征	SERINC2 表达		P值
临床特征	低表达≤3	高表达>3	P值
性别
男性	4	24	0.153
女性	9	17
年龄(岁)			0.106
<60	7	12
≥60	6	29
肿瘤大小			0.776
<3	5	14
≥3	8	27
部位			0.750
胰头	7	20
胰颈/体和胰尾	6	21
组织学分级			0.022
未分化/低分化	5	30
中至高分化	8	11
转移			0.046
是	6	31
否	7	10
中位生存时间(月)	50.52	19.67	0.029

泛癌分析SERINC2作为肿瘤预后和免疫生物标志物的潜力

Potential of SERINC2 as a biomarker in tumor prognosis and immunology: analysis from pan-cancer studies

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基因	log₂FC	基因	log₂FC
PHLDA2	3.625376216	JMJD7	-2.584352929
TOR4A	2.511431149	PTK6	2.738956129
TSPAN1	4.969836471	SDC4	2.819910909
GRN	2.49084516	PCDH1	2.065324205
LAMC2	5.23345125	CSTB	2.823136423
PMEPA1	2.768418245	GPRC5A	4.605598096
PMM2	-2.365271347	S100A11	4.432662328
PKM	2.083120818	B3GNT3	4.062210622
CAMK2N1	3.709835089	EPN1	-2.219356621
SDC1	3.996957566	KRT19	5.807400724
CRACR2B	-3.221081178	STXBP2	-2.169127568
PERP	2.724994459	GJB3	3.65057308
LAMB3	5.419575131	KRT7	2.424051902
TMEM54	2.026453582	SLC16A3	2.375866312
LAD1	2.048212032	S100A16	3.806831295
EPHA2	2.771953672	TMEM92	2.26323748
S100A14	4.042778947	CDCP1	2.179842041
S100A10	3.300436273	CAP1	2.265868342
LIPH	2.777629075	VDR	2.387111346
FUT3	2.027856195	TACSTD2	2.411679029
PPDPF	2.090795661	PLEC	2.211375587
SH3BGRL3	2.180435875