Cancer Biomarkers - Volume 34, issue 2

Authors: He, Yu-Zheng | Yu, Shan-Ling | Li, Xiao-Ning | Bai, Xian-Hua | Li, Hai-Tao | Liu, Yan-Chao | Lv, Bao-Lei | Zhao, Xiu-Min | Wei, Dong | Zhang, He-Lin | Li, Fan-Nian | Li, GuoLei | Li, Shuai

Article Type: Research Article

Abstract: Drug resistance is a critical factor responsible for the recurrence of non-small cell lung cancer (NSCLC). Previous studies suggest that curcumin acts as a chemosensitizer and radiosensitizer in human malignancies, but the underlying mechanism remains elusive. In the present study, we explored how curcumin regulates the expression of miR-142-5p and sensitizes NSCLC cells to crizotinib. We found that miR-142-5p is significantly downregulated in NSCLC tissue samples and cell lines. Curcumin could increase crizotinib cytotoxicity by epigenetically restoring the expression of miR-142-5p. Furthermore, curcumin treatment suppressed the expression of DNA methylation-related enzymes, including DNMT1, DNMT3A, and DNMT3B, in NSCLC cells. In …addition, the upregulation of miR-142-5p expression increased crizotinib cytotoxicity and induced apoptosis in tumor cells in a similar manner to that of curcumin. Strikingly, miR-142-5p overexpression suppressed crizotinib-induced autophagy in A549 and H460 cells. Mechanistically, miR-142-5p inhibited autophagy in lung cancer cells by targeting Ulk1. Overexpression of Ulk1 abrogated the miR-142-5p-induced elevation of crizotinib cytotoxicity in A549 and H460 cells. Collectively, our findings demonstrate that curcumin sensitizes NSCLC cells to crizotinib by inactivating autophagy through the regulation of miR-142-5p and its target Ulk1. Show more

Keywords: Non-small cell lung cancer, autophagy, miR-142-5p, curcumin, crizotinib

DOI: 10.3233/CBM-210282

Citation: Cancer Biomarkers, vol. 34, no. 2, pp. 297-307, 2022

Authors: He, Shuai | Li, Jin-Feng | Tian, Hao | Sang, Ye | Yang, Xiao-Jing | Guo, Gui-Xin | Yang, Jin-E

Article Type: Research Article

Abstract: BACKGROUND: Early recurrence is the main obstacle for long-term survival of hepatocellular carcinoma (HCC) patients after curative resection. OBJECTIVE: We aimed to develop a long non-coding RNA (lncRNA) based signature to predict early recurrence. METHODS: Using bioinformatics analysis and quantitative reverse transcription PCR (RT-qPCR), we screened for lncRNA candidates that were abnormally expressed in HCC. The expression levels of candidate lncRNAs were analyzed in HCC tissues from 160 patients who underwent curative resection, and a risk model for the prediction of recurrence within 1 year (early recurrence) of HCC patients was constructed with …linear support vector machine (SVM). RESULTS: An lncRNA-based classifier (Clnc), which contained nine differentially expressed lncRNAs including AF339810, AK026286, BC020899, HEIH, HULC, MALAT1, PVT1, uc003fpg, and ZFAS1 was constructed. In the test set, this classifier reliably predicted early recurrence (AUC, 0.675; sensitivity, 72.0%; specificity, 63.1%) with an odds ratio of 4.390 (95% CI, 2.120–9.090). Clnc showed higher accuracy than traditional clinical features, including tumor size, portal vein tumor thrombus (PVTT) in predicting early recurrence (AUC, 0.675 vs 0.523 vs 0.541), and had much higher sensitivity than Barcelona Clinical Liver Cancer (BCLC; 72.0% vs 50.0%), albeit their AUCs were comparable (0.675 vs 0.678). Moreover, combining Clnc with BCLC significantly increased the AUC, compared with Clnc or BCLC alone in predicting early recurrence (all P < 0.05). Finally, logistic and Cox regression analyses suggested that Clnc was an independent prognostic factor and associated with the early recurrence and recurrence-free survival of HCC patients after resection, respectively (all P = 0.001). CONCLUSIONS: Our lncRNA-based classifier Clnc can predict early recurrence of patients undergoing surgical resection of HCC. Show more

Keywords: Hepatocellular carcinoma, prognosis, lncRNA-based classifier, recurrence

DOI: 10.3233/CBM-210193

Citation: Cancer Biomarkers, vol. 34, no. 2, pp. 309-318, 2022

Authors: Vishwakarma, Gajendra K. | Kumari, Pragya | Bhattacharjee, Atanu

Article Type: Research Article

Abstract: BACKGROUND: HER2, ER, PR, and ERBB2 play a vital role in treating breast cancer. These are significant predictive and prognosis biomarkers of breast cancer. OBJECTIVE: We aim to obtain a unique biomarker-specific prediction on overall survival to know their survival and death risk. METHODS: Survival analysis is performed on classified data using Classification and Regression Tree (CART) analysis. Hazard ratio and Confidence Interval are computed using MLE and the Bayesian approach with the CPH model for univariate and multivariable illustrations. Validation of CART is executed with the Brier score, and accuracy and sensitivity …are obtained using the k-nn classifier. RESULTS: Utilizing CART analysis, the cut-off value of continuous-valued biomarkers HER2, ER, PR, and ERBB2 are obtained as 14.707, 8.128, 13.153, and 6.884, respectively. Brier score of CART is 0.16 towards validation of methodology. Survival analysis gives a demonstration of the survival estimates with significant statistical strategies. CONCLUSIONS: Patients with breast cancer are at low risk of death, whose HER2 value is below its cut-off value, and ER, PR, and ERBB2 values are greater than their cut-off values. This comparison is with the patient having the opposite side of these cut-off values for the same biomarkers. Show more

Keywords: Cancer, biomarker, bayesian, boosting, survival, classification

DOI: 10.3233/CBM-210470

Citation: Cancer Biomarkers, vol. 34, no. 2, pp. 319-328, 2022

Authors: Ergun, Yakup | Esen, Selin Akturk | Bardakci, Murat | Ucar, Gokhan | Kalkan, Ziya | Urakci, Zuhat | Seyran, Erdogan | Dogan, Mutlu | Eren, Tulay | Aslan, Volkan | Kahraman, Seda | Genc, Emine Eylem | Acikgoz, Yusuf | Dirikoc, Merve | Esen, Irfan | Uncu, Dogan

Article Type: Research Article

Abstract: BACKGROUND: The relationship of the ABO blood group system with the immune response is known, but its relationship with immune checkpoint inhibitors (ICIs) has not been clearly investigated until now. OBJECTIVE: In this study, the relationship between different blood groups and nivolumab treatment response in patients with advanced malignant melanoma was investigated. METHODS: The data of patients who used nivolumab for advanced malignant melanoma between April 2018 and April 2021 were retrospectively reviewed. RESULTS: A total of 73 patients were included in the study. In the progression-free survival (PFS) analysis according …to blood groups, it was 3.9 months, 16.1 months, 20.0 months and 3.0 months for A, B, AB and O, respectively (p = 0.1). Overall survival (OS) analysis according to blood groups was 5.1 months, 25.0 months, 20.0 months and 9.3 months for A, B, AB and O, respectively (p = 0.1). The B antigen group (B or AB) had significantly longer PFS and OS than the non-B antigen group (A or O) (16.1 vs. 3.5 months for PFS, respectively, p = 0.03; 20.0 vs. 7.4 months for OS, respectively, p = 0.02). CONCLUSIONS: The presence of B antigen provides a significant advantage in terms of survival in patients using ICIs for advanced melanoma. Show more

Keywords: Immune checkpoint inhibitor, nivolumab, ABO blood group, predictive, biomarker

DOI: 10.3233/CBM-210455

Citation: Cancer Biomarkers, vol. 34, no. 2, pp. 329-336, 2022