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. 2023 Feb 27;11(3):719.
doi: 10.3390/biomedicines11030719.

Expression Levels of GHRH-Receptor, pAkt and Hsp90 Predict 10-Year Overall Survival in Patients with Locally Advanced Rectal Cancer

Dávid Fodor  1 , Éva Pozsgai  2   3 , Andrew V Schally  4 , Zoltán László  5 , Éva Gömöri  6 , Éva Szabó  7 , László Rumi  8 , Dorottya Lőcsei  1 , Árpád Boronkai  1 , Szabolcs Bellyei  1
Affiliations

Expression Levels of GHRH-Receptor, pAkt and Hsp90 Predict 10-Year Overall Survival in Patients with Locally Advanced Rectal Cancer

Dávid Fodor et al. Biomedicines. .

Abstract

Background: Rectal cancer constitutes nearly one-third of all colorectal cancer diagnoses, and certain clinical and molecular markers have been studied as potential prognosticators of patient survival. The main objective of our study was to investigate the relationship between the expression intensities of certain proteins, including growth-hormone-releasing hormone receptor (GHRH-R), Hsp90, Hsp16.2, p-Akt and SOUL, in specimens of locally advanced rectal cancer patients, as well as the time to metastasis and 10-year overall survival (OS) rates. We also investigated whether these outcome measures were associated with the presence of other clinical parameters.

Methods: In total, 109 patients were investigated retrospectively. Samples of pretreatment tumors were stained for the proteins GHRH-R, Hsp90, Hsp16.2, p-Akt and SOUL using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationships between the intensity of expression of biomarkers, clinical parameters, the time to metastasis and the 10-year OS rate.

Results: High levels of p-Akt, GHRH-R and Hsp90 were associated with a significantly decreased 10-year OS rate (p = 0.001, p = 0.000, p = 0.004, respectively) and high expression levels of p-Akt and GHRH-R were correlated with a significantly shorter time to metastasis. Tumors localized in the lower third of the rectum were linked to both a significantly longer time to metastasis and an improved 10-year OS rate.

Conclusions: Hsp 90, pAkt and GHRH-R as well as the lower-third localization of the tumor were predictive of the 10-year OS rate in locally advanced rectal cancer patients. The GHRH-R and Hsp90 expression levels were independent prognosticators of OS. Our results imply that GHRH-R could play a particularly important role both as a molecular biomarker and as a target for the anticancer treatment of advanced rectal cancer.

Keywords: GHRH-R; Hsp90; neoadjuvant radiochemotherapy; overall survival; predictive markers; rectal cancer.

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Conflict of interest statement

The authors declare that they have neither financial nor non-financial competing nor conflicting interests.

Figures

Figure 1
Figure 1
The relationship between the staining intensity of the pretreatment proteins (a) p-Akt (p = 0.001), (b) GHRH-R (p = 0.000), (c) Hsp90 (p = 0.004) (d) SOUL (p = 0.661) and (e) Hsp16.2 (p = 0.975) and the 10-year OS rate. The effects of biological markers on the overall survival were demonstrated using Kaplan–Meier curves and the level of significance was determined using the log-rank test. Probability (p) values < 0.05 were considered statistically significant.
Figure 1
Figure 1
The relationship between the staining intensity of the pretreatment proteins (a) p-Akt (p = 0.001), (b) GHRH-R (p = 0.000), (c) Hsp90 (p = 0.004) (d) SOUL (p = 0.661) and (e) Hsp16.2 (p = 0.975) and the 10-year OS rate. The effects of biological markers on the overall survival were demonstrated using Kaplan–Meier curves and the level of significance was determined using the log-rank test. Probability (p) values < 0.05 were considered statistically significant.
Figure 2
Figure 2
The relationships between clinical parameters including the (a) histopathological response (p = 0.029), (b) tumor localization (p = 0.015), (c) gender (p = 0.057) (d) time to surgery (p = 0.568) and 10-year OS rate. The effects of the clinical parameters on the overall survival were demonstrated using Kaplan–Meier curves and the level of significance was determined using the log-rank test. Probability (p) values < 0.05 were considered statistically significant.
Figure 3
Figure 3
The relationship between the staining of the pretreatment proteins (a) p-Akt (p = 0.000), (b) GHRH-R (p = 0.000), (c) Hsp90 (p = 0.115), (d) SOUL (p = 0.310) and (e) Hsp16.2 (p = 0.328) and the time to metastasis. The effects of biological markers on the time to metastasis were demonstrated using Kaplan–Meier curves and the level of significance was determined using the log-rank test. Probability (p) values < 0.05 were considered statistically significant.
Figure 3
Figure 3
The relationship between the staining of the pretreatment proteins (a) p-Akt (p = 0.000), (b) GHRH-R (p = 0.000), (c) Hsp90 (p = 0.115), (d) SOUL (p = 0.310) and (e) Hsp16.2 (p = 0.328) and the time to metastasis. The effects of biological markers on the time to metastasis were demonstrated using Kaplan–Meier curves and the level of significance was determined using the log-rank test. Probability (p) values < 0.05 were considered statistically significant.
Figure 4
Figure 4
The relationships between clinical parameters including the (a) histopathological response (p = 0.170), (b) tumor localization (p = 0.048), (c) gender (p = 0.064), (d) time to surgery (p = 0.319) and time to metastasis. The effects of clinical parameters on the time to metastasis were demonstrated using Kaplan–Meier curves and the level of significance was determined using the log-rank test. Probability (p) values < 0.05 were considered statistically significant.
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