Cancer Biomarkers - Volume 23, issue 2

Authors: Deng, Lan | Jiang, Ling | Tseng, Kuo-Fu | Liu, Yuan | Zhang, Xing | Dong, Ruihong | Lu, Zhigang | Wang, Xiuju

Article Type: Research Article

Abstract: BACKGROUND: Many studies have demonstrated that the long non-coding RNA (lncRNA), NEAT1_1, plays critical roles in various human tumor entities and is related to the survival of patients with malignancies. However, the role of NEAT1_1 in diffuse large B cell lymphoma (DLBCL) remains unclear. The aim of this study was to investigate the role of NEAT1_1 in DLBCL. METHODS: The expression of NEAT1_1 was evaluated in paraffin-embedded tissues from 64 DLBCL patients and 15 lymphnoditis patients using the ISH method. The correlations between the expression levels of NEAT1_1 and clinical-pathological features and patients’ survival were also …analyzed. After knocking down NEAT1_1 using shRNA in the DLBCL cell lines OCI-Ly1 and SUDHL-4, cell viability, apoptosis and migration were assessed by performing CCK8 assays, annexin V-FITC/PI double staining assays and migration filter assays, respectively. RESULTS: NEAT1_1 expression was increased in DLBCL tissue compared to lymphnoditis tissue samples (P < 0.001). The NEAT1_1 level was positively related to stage (P = 0.031), IPI (P = 0.017), extranodal site involvement (P = 0.042) and drug response (P = 0.040). Kaplan-Meier analysis showed that high expression levels of NEAT1_1 were correlated with a poor prognosis in DLBCL patients. After shRNA-NEAT1_1 was transfected into OCI-Ly1 and SUDHL-4 for 24 h, the NEAT1_1 level decreased to approximately one-third the level of the control. Moreover, the viability and migration ability of the DLBCL cell lines were significantly suppressed. shRNA-NEAT1_1 induced apoptosis in both DLBCL cell lines. CONCLUSIONS: Our results showed that NEAT1_1 plays an oncogenic role in DLBCL. NEAT1_1 expression may serve as a predictive marker for DLBCL patients. Show more

Keywords: Diffuse large B cell lymphoma, long non-coding RNA, NEAT1_1

DOI: 10.3233/CBM-160221

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 157-164, 2018

Authors: Si, Pilei | Xu, Ye | Ouyang, Tao | Li, Jinfeng | Wang, Tianfeng | Fan, Zhaoqing | Fan, Tie | Lin, Benyao | Xie, Yuntao

Article Type: Research Article

Abstract: PURPOSE: To investigate the association between the HER2 germline mutation Ala270Ser (A270S), located in HER2 extracellular domain, and survival in breast cancer patients. METHODS: HER2 germline mutation A270S was identified in 5395 consecutive patients with operable primary breast cancer using direct Sanger sequencing analysis. Survival curves for patients with HER2 A270S mutation were compared using the Kaplan-Meier method with log-rank test. RESULTS: We identified that 31 cases carried HER2 germline mutation A270S in 5395 patients (0.6%, 31/5395). The HER2 A270S mutation was significantly associated with recurrence-free survival (RFS) and distant recurrence-free survival (DRFS) …in the entire cohort of 5395 patients (RFS, unadjusted hazard ratio [HR] = 2.23; 95% confidence interval [CI] = 1.00–5.00; P = 0.045; DRFS, unadjusted HR = 2.80; 95% CI = 1.25–6.28; P = 0.009). Among the HER2-negative patients (n = 3825), those with the HER2 A270S mutation had a significantly worse RFS (unadjusted HR = 3.19; 95% CI = 1.42–7.16; P = 0.003) and DRFS (unadjusted HR = 3.98; 95% CI = 1.77–8.96; P < 0.001) than did those with wild type. Moreover, the A270S mutation remained an independent unfavorable factor for RFS and DRFS in the HER2-negative patients (RFS, HR = 3.30; 95% CI = 1.34–8.10; P = 0.009; DRFS, HR = 4.26; 95% CI = 1.73–10.47; P = 0.002). CONCLUSIONS: Breast cancer patients with the HER2 germline mutation A270S had a worse survival, especially in HER2-negative patients. Therefore, HER2-negative patients with a HER2 germline mutation A270S might be potential candidates for HER2-targeted therapy. Show more

Keywords: Breast cancer, prognosis, HER2, germline mutation

DOI: 10.3233/CBM-170466

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 165-171, 2018

Authors: Cui, Ying | Tong, Shan-Shan | Zhang, Yan-Hong | Li, Hui-Ting

Article Type: Research Article

Abstract: OBJECTIVE: In order to improve the understanding of granular cell tumor and avoid missing the best time of treatment, we report three patients with rare granular cell tumors admitted to our hospital in the past 10 years. METHODS: The characteristics, methods of treatment, postoperative pathological results and follow-up results of three cases of granular cell tumor were analyzed; and literatures related to granular cell tumors were reviewed. RESULTS: All patients underwent surgical treatment, and the excised lesions were sent to the laboratory for testing. Postoperative pathological results were as follows: granular cell tumor of …the vulva, granular cell tumor within the sheath of the rectus muscle, and granular cell tumor in the left cubit nerve. All three cases were benign, and no recurrence was found during follow-ups after the operation. CONCLUSION: Granular cell tumors are rare tumors derived from the nerve sheath, are mostly benign tumors, and the incidence of malignancy is 2%. The gold standard for diagnosis of granular cell tumor is histopathology. Granular cell tumor is not sensitive to radiotherapy and chemotherapy, and needs to be surgically removed. Since this disease may have no solid lesions and tumor cells can infiltrate local tissues, based on the full excision of the lesion, the extent of resection may be extended to areas without infiltration. This disease has a possibility of recurrence, and patients need to be followed-up. Show more

Keywords: Granular cell tumor, vulva, right rectus sheath, left wrist nerve

DOI: 10.3233/CBM-170556

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 173-178, 2018

Authors: Zhang, Jing | Pei, Jing | Liu, Hong

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to explore the positive rate of non-visualized sentinel lymph nodes (non-vSLN) [1] in breast cancer (BC) patients and the discrepancy of non-vSLN among different molecular subtypes, in order to further evaluate the clinical risk of non-vSLNs. METHODS: A total of 627 patients were retrospectively analyzed. These patients were pathologically confirmed with invasive breast cancer and underwent sentinel lymph node biopsy (SLNB). Various factors were compared using chi-square test. The positive rate of SLNs between non-vSLNs and visible sentinel lymph nodes (vSLNs) were compared. Moreover, factors that influenced the prognosis, such as ER, …PR, HER-2, histological grade and lymph node metastasis were compared between these two groups. RESULTS: Among the 627 patients who underwent SLNB, 196 patients had non-vSLNs, accounting for 31.26% (196/627) and 113 patients had positive SLNs, accounting for 18.02% (113/627). Furthermore, 40.71% (46/113) of patients with positive SLNs had non-vSLN, and 17.39% (8/46) of patients with non-vSLN had HER-2+BC. In contrast, 35.82% (24/67) of patients with vSLNs had HER-2+BC. Moreover, 23.91% (11/46) of patients with non-vSLN and 5.97% (4/67) of patients with vSLNs had triple-negative breast cancer (TNBC). The metastasis rate was 41.30% (19/46) in the non-vSLN group and 43.28% (29/67) in the vSLN group. The difference in the rate of positive SLNs between the non-vSLN and the vSLN groups was statistically significant (P < 0.05), in which the positive rate of SLNs in the non-vSLN group was remarkably higher than that in the vSLN group. The differences in the proportion of HER-2+BC and TNBC between the non-vSLN and the vSLN groups were statistically significant (P < 0.05), in which HER-2+BCwas evidently higher in the vSLN group than in the non-vSLN group. Meanwhile, TNBC was markedly higher in non-vSLN group than in the vSLN group. Furthermore, differences in Luminal A subtype, Luminal B subtype and non-SLN metastasis between these two groups was not statistically significant. In addition, the difference in non-SLN metastasis rate was not statistically significant among breast cancers of different molecular subtypes and between the non-vSLN and the vSLN groups. CONCLUSION: Breast cancer patients with positive non-vSLNs are more likely to have a TNBC subtype relative to patients with positive vSLN. Breast cancer patients with non-vSLN have higher positive rate of SLNs. The non-SLN metastasis rate in positive SLN patients was not correlated to the molecular subtype of breast cancer. Show more

Keywords: Breast cancer, non-visible, sentinel lymph node, risk analysis, molecular subtype

DOI: 10.3233/CBM-170958

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 179-183, 2018

Authors: Zhou, Tao | Zhong, Meijun | Zhang, Shuyong | Wang, Zhi | Xie, Rong | Xiong, Chengfeng | Lv, Yunxia | Chen, Wanzhi | Yu, Jichun

Article Type: Research Article

Abstract: BACKGROUND: Long non-coding RNAs (lncRNAs) were recently identified as crucial regulators of papillary thyroid cancer (PTC). However, the clinical role and regulatory functions of lncRNA cancer susceptibility candidate 2 (CASC2) in PTC remain unknown. METHODS: LncRNA CASC2 expression was examined in plasma samples from 68 PTC patients and 39 patients with nodular goiter (NG). Cell proliferation, migration and invasion abilities were evaluated using CCK8 assay and transwell migration and invasion assay. QRT-PCR and western blot analysis were performed to detect the expression of epithelial-to-mesenchymal (EMT) markers ZEB1, E-cadherin and vimentin in PTC cells. RESULTS: …We demonstrated that lncRNA CASC2 expression was significantly downregulated in tumor tissues and plasma samples in patients with PTC compared with those in nodular goiters (P < 0.05). Decreased plasma lncRNA CASC2 expression associated with lymph node metastasis (LNM) of PTC patients and was identified as an independent risk for patients with LNM (P < 0.05). Furthermore, functional assays demonstrated that overexpression of lncRNA CASC2 inhibited cell proliferation, migration and invasion of PTC. Moreover, we demonstrated that overexpression of lncRNA CASC2 suppressed cell epithelial-mesenchymal transition (EMT) process of PTC by increasing the E-cadherin expression, but downregulating ZEB1 and N-cadherin expression. CONCLUSIONS: Thus, these results indicated that lncRNA CASC2 was a predictor for LNM of PTC patients and may serve as a potential target of PTC treatment. Show more

Keywords: Long non-coding RNA, CASC2, papillary thyroid cancer, lymph node metastasis

DOI: 10.3233/CBM-181198

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 185-191, 2018

Authors: Wang, Juan | Zhang, Huo | Zhou, Xin | Wang, Tongshan | Zhang, JinYing | Zhu, Wei | Zhu, Hong | Cheng, Wenfang

Article Type: Research Article

Abstract: BACKGROUND: Circulating microRNAs (miRNAs) have been implicated as novel biomarkers for various types of cancers. The aim of the study is to identify serum miRNAs with potential in detecting gastric cardia adenocarcinoma (GCA). METHODS: A three-phase study was designed with 102 GCA patients and 84 cancer-free controls. In the screening phase (3 GCA pools vs. 1 normal control (NC) pool), a total of 35 miRNAs were identified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel. Subsequently, these miRNAs were further assessed by qRT-PCR in the training phase (30 GCAs vs. 30 NCs) and …testing phase (72 GCAs vs. 54 NCs). Finally, the expression levels of the identified miRNAs were assessed in GCA tissues and exosomes. RESULTS: Five up-regulated miRNAs (miR-200a-3p, miR-296-5p, miR-132-3p, miR-485-3p and miR-22-5p) were identified in serum of the GCA patients compared with NCs. The areas under the receiver operating characteristic curve (AUCs) of the five-miRNA panel were 0.766 and 0.724 for the training and testing phases, respectively. In addition, miR-200a-3p, miR-296-5p, miR-485-3p and miR-22-5p were significantly up-regulated in GCA tissues. However, none of the miRNAs in the exosomes showed different expression between GCA patients and NCs. CONCLUSIONS: We identified a five-miRNA panel in peripheral serum samples as a non-invasive biomarker in detection of GCA. Show more

Keywords: Serum, microRNA, gastric cardia adenocarcinoma, diagnostic biomarker

DOI: 10.3233/CBM-181258

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 193-203, 2018

Authors: Huang, Yiru | Cui, Ming-Ming | Huang, Yuan-Xi | Fu, Shuang | Zhang, Xin | Guo, Hongbo | Wang, Rui-Tao

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer is one of the most commonly diagnosed cancers, and the fourth leading cause of cancer deaths in females worldwide. Activated platelets play a key role in tumor growth and tumor metastasis. Platelet distribution width (PDW) is a platelet index, and is altered in patients with malignancies. The aim of this study was to explore whether PDW can effectively predict death outcome of breast cancer patients. STUDY DESIGN: The clinical data of 271 breast cancer patients in our hospital between January 2009 and December 2009 were retrospectively analyzed. Survival analysis was performed using the …log-rank test and Cox proportional hazards regression analysis. RESULT: There were significant correlations between increased PDW and tumor size, molecular subtype, differentiation grade, and cancer stages (T, N, or TNM). Moreover, survival analysis revealed that the overall survival of patients with PDW > 16.8%, which was significantly shorter than those with PDW ⩽ 16.8%. Multivariate analysis indicated that PDW > 16.8% predicts a poor overall survival of breast cancer patients. CONCLUSIONS: Elevated PDW may serve as a marker of adverse prognosis in breast cancer. However, these data are preliminary and should be interpreted with caution pending validation by additional clinical and molecular/genomics studies in various populations. Show more

Keywords: Breast cancer, platelet distribution width, prognosis

DOI: 10.3233/CBM-181267

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 205-211, 2018

Authors: Xu, Yong-Hua | Liu, Shuo-Hui | Hao, Fu-Rong | Zhang, Yin-Huan

Article Type: Research Article

Abstract: OBJECTIVE: Lymphoma is considered to be a kind of malignant tumour. Gene therapy and radiotherapy have been reported as treatment methods for head and neck lymphoma. This study aims to evaluate the efficacy and safety for the treatment of head and neck lymphoma by a combination of recombinant adenovirus p53 (rAd-p53) and radiotherapy. METHODS: A total of 156 patients with head and neck lymphoma were selected. All patients received an intratumor injection of rAd-p53 of four different doses, namely, 0, 1 × 10 10 VP, 1 × …10 11 VP and 1 × 10 12 VP, once a week for 8 weeks, and radiotherapy was administered 3 days after the rAd-p53 injection using the same dosage and method. Four, eight and twelve weeks after treatment, tumor reduction and complete response (CR) rates, special laboratory examination and adverse reaction assessment were detected to evaluate the efficacy and safety of combined treatment with rAd-p53 injection and radiotherapy for head and neck lymphoma. RESULTS: At week 4, 8 and 12 of treatment with rAd-p53 at the 1 × 10 10 VP, 1 × 10 11 VP and 1 × 10 12 VP doses, the average tumour reduction and CR rates were evidently elevated, the anti rAd-p53 antibody in the serum of patients was expressed positively, and the T cell subsets (CD3/CD4/CD8) increased and interleukin 2 receptor (IL-2R) level decreased markedly. Additionally, rAd-p53 was proven to be clinically safe in the treatment. CONCLUSION: Altogether, we conclude that rAd-p53 combined with radiotherapy improves the efficacy and safety in treating head and neck lymphoma, which has a broad scope in future clinical application. Show more

Keywords: Head and neck lymphoma, recombinant adenovirus p53, radiotherapy, efficacy, safety, adverse reaction

DOI: 10.3233/CBM-181286

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 213-220, 2018

Authors: Farhangian, Pourandokht | Jahandoost, Somayeh | Mowla, Seyed Javad | Khalili, Mitra

Article Type: Research Article

Abstract: BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer-related death in the world. Dysfunction of long noncoding RNAs (lncRNAs) in cancers, especially those with role in pluripotency, are approved by increasing evidence. OBJECTIVE: SOX2 overlapping transcript (SOX2OT ) lncRNA, is aberrantly expressed in different cancers; however its role in gastric cancer is still controversial. MATERIALS AND METHODS: In this study, the expression of SOX2OT was evaluated in 33 matched pair tumor and non-tumor gastric samples and AGS and MKN45 gastric and NTERA2 embryonic carcinoma cell lines by real time PCR. …RESULTS: Our finding revealed a significant decrease in the expression of SOX2OT in gastric tumor samples compared to their matched non-tumor samples (P = 0.05) and also a lower expression in high grade compared to low grade of gastric malignancy. As we expected SOX2OT expression showed higher expression in NT2 compared to AGS and MKN45 cell lines. CONCLUSION: Simultaneous expression of SOX2 and SOX2OT was reported in some cancers. Regarding to the decreased expression of SOX2OT in the present study in concurrent with downregulation of SOX2 in our previous study, it seems that SOX2OT plays a tumor suppressor role in GC and may be useful biomarker for diagnosis of GC. Show more

Keywords: Long Non Coding RNA, SOX2OT, Gastric Cancer, SOX2

DOI: 10.3233/CBM-181325

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 221-225, 2018

Authors: Liu, Yang | Li, Lin | Yu, Jie | Fan, Yu-Xia | Lu, Xiu-Bo

Article Type: Research Article

Abstract: BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy which is generally accompanied by lymph node metastasis. OBJECTIVE: Our study evaluated whether carbon nanoparticle lymph node tracer can improve the outcomes of surgical treatment in papillary thyroid cancer (PTC). METHODS: Ninety-two patients were selected and underwent total thyroidectomy and lymph node resection. Our study placed 45 individuals into the treatment group (carbon nanoparticle group) and 47 cohorts in the control group (no carbon nanoparticle group). RESULTS: Carbon nanoparticle application remarkably improved lymph nodes detection rate in patients (4.7 …± 3.0; P < 0.05) compared to those in control groups (3.5 ± 2.3). The rate of parathyroid accidental resection in the carbon nanoparticle group significantly decreased (6.67%) compared to the control group (21.28%). Incidents of hypoparathyroidism and hypocalcaemia significantly decreased among the carbon nanoparticle cohorts. CONCLUSIONS: Our study definitively showed that carbon nanoparticles can be used to effectively treat lymphatic carcinoma. Our study presented clinical evidences for potential application of carbon nanoparticle in improving the management of PTC patients. Show more

Keywords: Thyroid cancer, papillary thyroid cancer, carbon nanoparticles, carbon nanoparticle lymph node tracer, central region lymph node dissection

DOI: 10.3233/CBM-181386

Citation: Cancer Biomarkers, vol. 23, no. 2, pp. 227-233, 2018