High ALDH-1 Expression Predicts Non-Complete Response of Radiotherapy in Stage III Squamous Cell Cervical Carcinoma Patients.

BACKGROUND ALDH1 is a cervical cancer stem cell marker that has radioresistance profile. Recurrence and metastasis following radiotherapy are still being problems of most patients. This study aimed to determine the correlation between ALDH1 and radiotherapy response in stage III squamous cell cervical carcinoma (SCCC) of the cervix. METHODS A total 58 of 360 patients of stage III SCCC who received external beem radiation and brachytherapy (2016-2021) at Cipto Mangunkusumo Hospital met the eligibility criteria of this study. Pre- and post-irradiation MRI examinations and ALDH expression with immunohistochemistry (Santa Cruz®) were performed on formalin-fixed paraffin-embedded of pre-treatment cervical tissue biopsy taken from RSCM pathological anatomy laboratory. Patients were divided into two groups, complete responders vs non-complete responders. ALDH-1 scores were compared between two groups to assess ALDH-1 expression. The statistical analyses were carried out by SPSS 24. RESULTS The optimal ALDH-1 score cut-off point on the radiation response was 166.05 pg/mL which was obtained from the analysis of the ROC curve. The AUC value was 0.682 with sensitivity and specificity, 63,6% and 64%, respectively. ALDH score ≥166.05 increased the risk by 3.127 times for not achieving complete response (adj OR 3.127, 95% CI 1.034 - 9.456, p = 0.043). Pre-radiation tumor size (p = 0.593), degree of differentiation (p = 0.161), renal abnormalities (p = 0.114), and keratinization (p = 0.477) were not associated with radiation response. CONCLUSIONS High ALDH expression was associated with non-complete radiation response in stage III squamous cell cervical carcinoma. .

[1]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[2]  Chunxian Huang,et al.  ALDH-1-positive cells exhibited a radioresistant phenotype that was enhanced with hypoxia in cervical cancer , 2020, BMC cancer.

[3]  A. Prijanti,et al.  Survivin and Telomerase as Radiotherapeutic Response Predictors of Subjects with Stage IIIB Cervical Squamous Cell Carcinoma , 2020 .

[4]  L. Nuranna,et al.  Survival Rate of Cervical Cancer in National Referral Hospital in 2012 - 2014. , 2019, Acta medica Indonesiana.

[5]  Ping Yang,et al.  Effect of radiotherapy on the survival of cervical cancer patients , 2019, Medicine.

[6]  S. Bardosono,et al.  Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer , 2019, Oman medical journal.

[7]  E. Rahakbauw,et al.  Radiotherapy response and related clinicopathological factors of patients with cervical cancer , 2018, Journal of Physics: Conference Series.

[8]  P. Shukla,et al.  Role of Histopathological Differentiation as a Prognostic Factor for Treatment Response in Locally Advanced Squamous Cell Carcinoma Cervix Patients , 2018, Indian Journal of Medical and Paediatric Oncology.

[9]  J. Prihartono,et al.  Reirradiation on recurrent cervical cancer case: Treatment response and side effects , 2017 .

[10]  E. Rofstad,et al.  Cancer stem cells (CSCs), cervical CSCs and targeted therapies , 2016, Oncotarget.

[11]  A. Dubrovska,et al.  A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms. , 2015, Seminars in cancer biology.

[12]  N. Magné,et al.  Targeting Head and Neck Cancer Stem Cells to Overcome Resistance to Photon and Carbon Ion Radiation , 2014, Stem Cell Reviews and Reports.

[13]  Brian C. Jackson,et al.  Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress. , 2013, Free radical biology & medicine.

[14]  C. Lengerke,et al.  Selection of radioresistant tumor cells and presence of ALDH1 activity in vitro. , 2011, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[15]  O. Abulafia,et al.  Hydronephrosis as a Prognostic Indicator of Survival in Advanced Cervix Cancer , 2011, International Journal of Gynecologic Cancer.

[16]  Shamshad Ali,et al.  Impact of hydronephrosis on outcome of stage IIIB cervical cancer patients with disease limited to the pelvis, treated with radiation and concurrent chemotherapy: a Gynecologic Oncology Group study. , 2010, Gynecologic oncology.

[17]  Yi-Wei Chen,et al.  Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer. , 2009, Biochemical and biophysical research communications.

[18]  Feng Jiang,et al.  Aldehyde Dehydrogenase 1 Is a Tumor Stem Cell-Associated Marker in Lung Cancer , 2009, Molecular Cancer Research.

[19]  M. Candelaria,et al.  CHEMORADIATION WITH GEMCITABINE FOR CERVICAL CANCER IN PATIENTS WITH RENAL FAILURE , 2004, International Journal of Gynecologic Cancer.