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Crosstalk of SPINK4 Expression With Patient Mortality, Immunotherapy and Metastasis in Pan-Cancer Based on Integrated
Xiuhua Cao1,2, Na Luo1, Xiaoyan Liu1
1Center for Basic Medical Research, Southwest Medical University, Luzhou, People's Republic of China.
Background:
Cancer remains a major global health challenge, with early detection and prompt treatment being crucial for reducing mortality rates. The SPINK4 has been linked to the development of several tumors, and there is growing evidence of its involvement. However, its specific functions and effects in different cancer types remain unclear.
Methods:
The association between SPINK4 expression levels and tumor progression was investigated and confirmed using the TCGA dataset. Kaplan-Meier curves were utilized to examine the correlation between SPINK4 expression with survival outcomes in pan-cancer patients. The Pearson method was employed to investigate the association of SPINK4 expression with the tumor microenvironment, stemness score, immunoinfiltrating subtype, and chemotherapy sensitivity in human different cancer types. Wound healing and Transwell assays were performed to confirm the roles of the model gene in colon adenocarcinoma cells.
Results:
The expression of SPINK4 shows heterogeneity across pan-cancer tissues, and is closely associated with poor prognosis, immune cell invasion, tumor cell resistance, and tumor metastasis in a various human cancer. Mutation of SPINK4 hold significant predictive value for poor prognosis of pan-cancer patients. In addition, SPINK4 expression was significantly correlated with the tumor microenvironment (stromal cells and immune cells) and stemness score (DNAss and RNAss) in human pan-cancer tissues, particularly in BLCA and COAD. Single-cell sequencing analysis showed that SPINK4 is mainly expressed in endothelial cells in BLCA and in malignant cells in COAD. Drug resistance analysis showed a significant association between SPINK4 expression and sensitivity to several cancer chemotherapy drugs. Importantly, overexpression of SPINK4 promoted the metastasis of colon cancer cell lines (HCT116 and RKO), whereas SPINK4 knockout markedly inhibited their metastasis.
Conclusion:
These findings reveal the crucial role of SPINK4 in the pan-cancer process and may have significant implications for the diagnosis and treatment of cancer in the future.
Insights
The gene SPINK4 is linked to poor cancer prognosis, immune cell invasion, and metastasis across various cancers. Its role in colon cancer progression highlights its potential as a diagnostic and therapeutic target.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Oncology
Background:
- Cancer remains a significant global health burden, necessitating advancements in early detection and treatment.
- The gene SPINK4 has been implicated in tumorigenesis, but its precise roles in diverse cancer types require further elucidation.
Purpose of the Study:
- To investigate the association between SPINK4 expression and tumor progression, survival outcomes, and the tumor microenvironment in pan-cancer patients.
- To explore the functional role of SPINK4 in colon adenocarcinoma cell metastasis.
Main Methods:
- Utilized TCGA dataset to analyze SPINK4 expression and its correlation with survival, tumor microenvironment, stemness, and chemotherapy sensitivity.
- Performed Kaplan-Meier survival analysis and Pearson correlation analysis.
- Conducted in vitro wound healing and Transwell assays to assess SPINK4 function in colon cancer cells.
Main Results:
- SPINK4 expression is heterogeneous across cancers and correlates with poor prognosis, immune cell invasion, drug resistance, and metastasis.
- SPINK4 mutations predict poor prognosis in pan-cancer patients.
- SPINK4 expression is linked to tumor microenvironment components and stemness scores, particularly in bladder carcinoma (BLCA) and colorectal adenocarcinoma (COAD).
- Overexpression of SPINK4 promotes colon cancer cell metastasis, while its knockout inhibits it.
Conclusions:
- SPINK4 plays a critical role in pan-cancer progression, influencing prognosis, immune evasion, and metastasis.
- SPINK4 may serve as a potential biomarker for cancer diagnosis and a therapeutic target for improving treatment outcomes.
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