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. 2025 Jan;13(1):e70192.
doi: 10.14814/phy2.70192.

Genome analysis uncovers an inverse correlation between alterations in P21-activated kinases and patient survival across multiple cancer types

Jessie M Vo  1 , Linh M La  1 , Ananda V Anderson  1 , Abdulaziz H Alanazi  1   2 , Payaningal R Somanath  1   3
Affiliations

Genome analysis uncovers an inverse correlation between alterations in P21-activated kinases and patient survival across multiple cancer types

Jessie M Vo et al. Physiol Rep. 2025 Jan.

Abstract

Cancer is a complex disease with profound societal and economic impacts, especially in metastatic cases where treatment challenges arise due to the absence of reliable biomarkers and effective therapies. While P21-activated kinases (PAKs) play a key role in cancer progression, their potential as predictive markers for metastasis and therapeutic targets has not been fully explored. We hypothesized that genetic alterations in PAK isoforms could be linked to reduced overall patient survival. To investigate this, we used data from the cBioPortal for Cancer Genomics, analyzing several randomized, multicentered phase-3 clinical trial datasets. The analysis revealed significant genetic alterations in PAK genes, particularly in cancers such as breast, prostate, pancreatic, and lung. Notably, elevated PAK expression was associated with poorer survival outcomes in prostate and breast cancer patients. In pancreatic and lung cancers, although a trend of poorer survival with PAK alterations was observed, it was not statistically significant. Our findings underscore the importance of PAK isoforms as potential biomarkers and therapeutic targets, particularly in metastatic cancers. Further research could lead to improved patient outcomes through targeted interventions aimed at PAK-related pathways, with PAK serving as a reliable biomarker for the precise diagnosis, monitoring, and personalization of treatment strategies.

Keywords: P21 activated kinase; cancer; genetic alterations; metastasis; patient survival.

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Conflict of interest statement

P.R.S. is the Co‐Founder and Chief Scientific Officer of MetasTx LLC.; other authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
DepMap analysis of the dependency of tumor cell line panels in CRISPR (blue) and RNAi (purple) databases on the indicated PAKS. X‐axis: Gene Effect.
FIGURE 2
FIGURE 2
cBioPortal analysis of frequencies of the indicated alterations of PAK1, PAK2, PAK3, PAK4, PAK5, and PAK6 (gene amplification red, deep deletion blue, mutation green) among different cancer subtypes.
FIGURE 3
FIGURE 3
cBioPortal oncoprints showing various alterations in PAK isoforms in different cancers. The percentages on the left‐hand side indicate frequencies of all alterations for the respective PAK.
FIGURE 4
FIGURE 4
(a–e) Bar graphs displaying the distribution of various mutation types in PAK isoforms across different cancer cell lines, analyzed from DepMap data. (f) Data summarizing the types of mutations in PAK isoforms across multiple cancer types, sourced from cBioPortal.
FIGURE 5
FIGURE 5
SRplot correlation matrix heatmap showing the extent of correlation between the expression of PAK isoforms in (a) prostate (b) breast (c) lung (d) pancreatic, and (e) skin cancers.
FIGURE 6
FIGURE 6
Kaplan–Meier plots correlating PAK1‐6 expression with a probability of survival in (a) prostate (b) breast (c) lung (d) pancreatic, and (e) skin cancers.
FIGURE 7
FIGURE 7
Kaplan–Meier plots correlating each PAK expression with a probability of survival in the case of prostate cancer.
FIGURE 8
FIGURE 8
Kaplan–Meier plots correlating each PAK expression with a probability of survival in the case of breast cancer.
FIGURE 9
FIGURE 9
Kaplan–Meier plots correlating each PAK expression with a probability of survival in the case of lung cancer.
FIGURE 10
FIGURE 10
Kaplan–Meier plots correlating PAK2, PAK3, and PAK4 expression with probability of survival in the case of pancreatic cancer.
FIGURE 11
FIGURE 11
Kaplan–Meier plots correlating each PAK expression with a probability of survival in the case of skin cancer.
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