Prognostic and Immunomodulatory Roles of PAK6 in Colorectal Cancer Through Integrative Transcriptomic and Clinical Analysis
Abstract
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Data Acquisition and Preprocessing
2.2. Expression Profiling and Diagnostic Evaluation
2.3. Clinical Correlation and Survival Analysis
2.4. Co-Expression Network and Functional Enrichment
2.5. Immune Microenvironment Characterization
2.6. Chemokine Interaction Network
2.7. Tissue Microarray and Immunohistochemistry
2.8. Statistical Analysis
3. Results
3.1. Aberrant Upregulation of PAK6 mRNA and Protein in Colorectal Cancer
3.2. Association of PAK6 with Aggressive Clinicopathological Features
3.3. Functional Enrichment Implicates PAK6 May Be Involved in Malignant Progression of CRC
3.4. PAK6 Expression Negatively Correlates with Tumor Microenvironment Scores and Influences Immune Cell Infiltration
3.5. PAK6 Is Linked to Immune Regulatory Genes and Checkpoint Molecules
3.6. PAK6 Is Associated with Chemokine Signaling and Immune Cell Migration
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | Total (N) | HR(95% CI) Univariate Analysis | p Value Univariate Analysis | HR (95% CI) Multivariate Analysis | p Value Multivariate Analysis |
---|---|---|---|---|---|
Pathologic T stage | 476 | ||||
T1 & T2 | 94 | Reference | Reference | ||
T3 & T4 | 382 | 3.072 (1.423–6.631) | 0.004 | 279,063.4392 (0.000–Inf) | 0.992 |
Pathologic N stage | 477 | ||||
N0 | 283 | Reference | Reference | ||
N1 & N2 | 194 | 2.592 (1.743–3.855) | <0.001 | 0.003 (0.000–0.078) | <0.001 |
Pathologic M stage | 414 | ||||
M0 | 348 | Reference | Reference | ||
M1 | 66 | 4.193 (2.683–6.554) | <0.001 | 0.956 (0.047–19.598) | 0.977 |
Pathologic stage | 466 | ||||
Stage I & Stage II | 267 | Reference | Reference | ||
Stage III & Stage IV | 199 | 2.947 (1.942–4.471) | <0.001 | 1,085,453,553.6095 (0.000–Inf) | 0.981 |
PAK6 | 477 | ||||
Low | 238 | Reference | Reference | ||
High | 239 | 1.803 (1.211–2.682) | 0.004 | 2.651 (0.251–28.041) | 0.418 |
Primary therapy outcome | 250 | ||||
PD&SD | 29 | Reference | Reference | ||
PR&CR | 221 | 0.094 (0.049–0.182) | <0.001 | 0.020 (0.002–0.168) | <0.001 |
Gender | 477 | ||||
Female | 226 | Reference | |||
Male | 251 | 1.101 (0.746–1.625) | 0.627 | ||
Age | 477 | ||||
≤65 | 194 | Reference | Reference | ||
>65 | 283 | 1.610 (1.052–2.463) | 0.028 | 2.372 (0.224–25.170) | 0.473 |
Histological type | 472 | ||||
Adenocarcinoma | 402 | Reference | |||
Mucinous adenocarcinoma | 70 | 1.269 (0.753–2.139) | 0.371 | ||
Residual tumor | 373 | ||||
R0 | 345 | Reference | Reference | ||
R1&R2 | 28 | 4.364 (2.401–7.930) | <0.001 | 1.625 (0.081–32.707) | 0.751 |
Perineural invasion | 181 | ||||
No | 135 | Reference | Reference | ||
Yes | 46 | 1.940 (0.982–3.832) | 0.056 | 1.147 (0.055–23.782) | 0.93 |
Lymphatic invasion | 433 | ||||
No | 265 | Reference | Reference | ||
Yes | 168 | 2.450 (1.614–3.720) | <0.001 | 17.373 (1.959–154.051) | 0.01 |
Characteristic | Levels | PAK6 Expression | p | |
---|---|---|---|---|
Low (n = 24) | High (n = 25) | |||
Gender | Male | 14 (28.6%) | 13 (26.5%) | 0.656 |
Female | 10 (20.4%) | 12 (24.5%) | ||
Age | <60 | 8 (16.3%) | 13 (26.5%) | 0.187 |
≥60 | 16 (32.7%) | 12 (24.5%) | ||
Differentiation | Well | 0 (0.0%) | 5 (10.2%) | 0.021 * |
Moderate | 24 (49.0%) | 20 (40.8%) | ||
Tumor size | <4 cm | 12 (24.5%) | 16 (32.7%) | 0.322 |
≥4 cm | 12 (24.5%) | 9 (18.4%) | ||
LVI | No | 15 (30.6%) | 13 (26.5%) | 0.458 |
Yes | 9 (18.4%) | 12 (24.5%) | ||
PNI | No | 19 (38.8%) | 17 (34.7%) | 0.376 |
Yes | 5 (10.2%) | 8 (16.3%) | ||
T stage | T1 + T2 | 4 (8.2%) | 4 (8.2%) | 0.95 |
T3 + T4 | 20 (40.8%) | 21 (42.9%) | ||
N stage | Negative | 15 (30.6%) | 14 (28.6%) | 0.644 |
Positive | 9 (18.4%) | 11 (22.4%) | ||
M stage | Negative | 20 (40.8%) | 19 (38.8%) | 0.524 |
Positive | 4 (8.2%) | 6 (12.2%) | ||
Stage | Early (I + II) | 12 (24.5%) | 12 (24.5%) | 0.889 |
Late (III + IV) | 12 (24.5%) | 13 (26.5%) |
Immune Cell Type | Coefficient of Correlation | p Value adj.* |
---|---|---|
NK CD56bright cells | 0.288948 | 9.9 × 10−9 |
NK CD56dim cells | 0.277894 | 2.6235 × 10−9 |
Th2 cells | 0.270829 | 4.89 × 10−9 |
aDC | 0.220401 | 0.00000243 |
NK cells | 0.207003 | 0.000008658 |
Cytotoxic cells | 0.177571 | 0.0001188 |
pDC | −0.177497 | 0.0001188 |
Tcm | −0.157958 | 0.0005625 |
TFH | 0.13176 | 0.0038 |
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Ye, C.; Yue, G.; Yang, L.; Wang, Z. Prognostic and Immunomodulatory Roles of PAK6 in Colorectal Cancer Through Integrative Transcriptomic and Clinical Analysis. Cancers 2025, 17, 3183. https://doi.org/10.3390/cancers17193183
Ye C, Yue G, Yang L, Wang Z. Prognostic and Immunomodulatory Roles of PAK6 in Colorectal Cancer Through Integrative Transcriptomic and Clinical Analysis. Cancers. 2025; 17(19):3183. https://doi.org/10.3390/cancers17193183
Chicago/Turabian StyleYe, Chunxiang, Guanjun Yue, Lei Yang, and Zhenjun Wang. 2025. "Prognostic and Immunomodulatory Roles of PAK6 in Colorectal Cancer Through Integrative Transcriptomic and Clinical Analysis" Cancers 17, no. 19: 3183. https://doi.org/10.3390/cancers17193183
APA StyleYe, C., Yue, G., Yang, L., & Wang, Z. (2025). Prognostic and Immunomodulatory Roles of PAK6 in Colorectal Cancer Through Integrative Transcriptomic and Clinical Analysis. Cancers, 17(19), 3183. https://doi.org/10.3390/cancers17193183