Scholarlink

Background <p>Hepatocellular carcinoma (HCC) remains biologically heterogeneous, and molecular states linking tumor-cell intrinsic programs with post-translational regulation, immune contexture and drug-specific vulnerability remain incompletely defined. ZDHHC16 is a DHHC-family palmitoyl acyltransferase, but its clinical relevance and biological context in HCC remain unclear.</p> Methods <p>Public transcriptomic, clinical, single-cell, proteomic, palmitoylome, immune-related and pharmacogenomic datasets were integrated to characterize ZDHHC16 in HCC. ZDHHC16 expression, exploratory survival separation, cellular localization, pathway activity, palmitoylation-associated candidates, immune microenvironment features and predicted drug response were evaluated. siRNA-mediated knockdown, MTT assays and colony formation assays were performed in HepG2 and Huh7 cells.</p> Results <p>ZDHHC16 was upregulated in HCC. In exploratory Kaplan-Meier analyses restricted to primary tumors and using endpoint-specific data-derived cutoffs, the curves showed expression-group separation for overall survival, disease-free interval and progression-free interval (unadjusted log-rank <i>P</i> = 0.019, 0.019 and 0.011, respectively). These analyses were not adjusted for clinical covariates and do not establish independent prognostic value. Single-cell analysis localized ZDHHC16 mainly to malignant epithelial-related compartments. ZDHHC16 knockdown reduced MTT-based cell viability and clonogenic growth in HepG2 and Huh7 cells. ZDHHC16-high tumors were enriched for cell-cycle progression, DNA replication, DNA repair, RNA processing, ubiquitin-mediated proteolysis and proteasome-related programs. After deduplication at the gene-symbol level, palmitoylome-guided integration nominated 28 transcriptionally correlated palmitoylation-associated candidates, including EZH2, PI4K2A and ZDHHC6; the screen did not establish direct ZDHHC16 substrates. ZDHHC16-high tumors also showed immune-remodeled features and drug-specific predicted IC50 patterns.</p> Conclusions <p>Integrated data support ZDHHC16 as a marker of a malignant epithelial, growth-associated HCC state accompanied by palmitoylation- and proteostasis-related programs, altered immune contexture and drug-specific predicted IC50 patterns. Direct ZDHHC16-dependent palmitoylation, independent prognostic value and therapeutic utility require biochemical and prospective clinical validation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Integrated multi-omic and functional profiling reveals a ZDHHC16-associated palmitoylation-proteostasis state in hepatocellular carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月1日

查看全文
  • Lihua Zhang,
  • Xiaolei Zhang,
  • Caiqi Liu,
  • Xiaofei Xin,
  • Xinchi Luan,
  • Jialin Song,
  • Wensheng Qiu

摘要

Background

Hepatocellular carcinoma (HCC) remains biologically heterogeneous, and molecular states linking tumor-cell intrinsic programs with post-translational regulation, immune contexture and drug-specific vulnerability remain incompletely defined. ZDHHC16 is a DHHC-family palmitoyl acyltransferase, but its clinical relevance and biological context in HCC remain unclear.

Methods

Public transcriptomic, clinical, single-cell, proteomic, palmitoylome, immune-related and pharmacogenomic datasets were integrated to characterize ZDHHC16 in HCC. ZDHHC16 expression, exploratory survival separation, cellular localization, pathway activity, palmitoylation-associated candidates, immune microenvironment features and predicted drug response were evaluated. siRNA-mediated knockdown, MTT assays and colony formation assays were performed in HepG2 and Huh7 cells.

Results

ZDHHC16 was upregulated in HCC. In exploratory Kaplan-Meier analyses restricted to primary tumors and using endpoint-specific data-derived cutoffs, the curves showed expression-group separation for overall survival, disease-free interval and progression-free interval (unadjusted log-rank P = 0.019, 0.019 and 0.011, respectively). These analyses were not adjusted for clinical covariates and do not establish independent prognostic value. Single-cell analysis localized ZDHHC16 mainly to malignant epithelial-related compartments. ZDHHC16 knockdown reduced MTT-based cell viability and clonogenic growth in HepG2 and Huh7 cells. ZDHHC16-high tumors were enriched for cell-cycle progression, DNA replication, DNA repair, RNA processing, ubiquitin-mediated proteolysis and proteasome-related programs. After deduplication at the gene-symbol level, palmitoylome-guided integration nominated 28 transcriptionally correlated palmitoylation-associated candidates, including EZH2, PI4K2A and ZDHHC6; the screen did not establish direct ZDHHC16 substrates. ZDHHC16-high tumors also showed immune-remodeled features and drug-specific predicted IC50 patterns.

Conclusions

Integrated data support ZDHHC16 as a marker of a malignant epithelial, growth-associated HCC state accompanied by palmitoylation- and proteostasis-related programs, altered immune contexture and drug-specific predicted IC50 patterns. Direct ZDHHC16-dependent palmitoylation, independent prognostic value and therapeutic utility require biochemical and prospective clinical validation.