高水平论文推送6——肿瘤学
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为促进学术交流与知识共享，助力科研人员及时了解各领域前沿动态与最新研究成果，现决定定期推送我校学者发表的高水平论文。每篇推送将包含论文题目、作者信息、发表期刊/会议、核心观点摘要、研究亮点及创新点等关键内容。
本期主题为肿瘤学，希望为相关研究者的学术研究提供有益参考，提升学术水平。请有关单位、部门加强学校高水平论文的推介工作。
科学技术部
2025年9月5日
奥沙利铂联合氟嘧啶新辅助化疗与直接手术治疗局部晚期结肠癌的对比：随机III期OPTICAL试验
Issue JOURNAL OF CLINICAL ONCOLOGY 2024, Volume 42 Issue 25
期刊：《临床肿瘤学杂志》2024年，第42卷第25期
Author Hu Huabin / Zhang Jianwei / Li Yunfeng / Wang Xiaozhong / Wang Ziqiang / Wang Hui / Kang Liang / Liu Ping / Lan Ping / Wu Xiaojian / Zhen Yunhuan / Pei Haiping / Huang Zhongcheng / Zhang Hao / Chen Wenbin / Zeng Yongming / Lai Jiajun / Wei Hongbo / Huang Xuefeng / Chen Jiansi / Chen Jigui / Tao Kaixiong / Xu Qingwen / Peng Xiang / Liang Junlin / Cai Guanfu / Ding Kefeng / Ding Zhijie / Hu Ming / Zhang Wei / Tang Bo / Hong Chuyuan / Cao Jie / Huang Zonghai / Cao Wuteng / Li Fangqian / Wang Xinhua / Wang Chao / Huang Yan / Zhao Yandong / Cai Yue / Ling Jiayu / Xie Xiaoyu / Wu Zehua / Shi Lishuo / Ling Li / Liu Hao / Wang Jianping / Huang Meijin / Deng Yanhong
Abstract
PURPOSEThe role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery.PATIENTS AND METHODSOPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat >= 5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population.RESULTSBetween January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]).CONCLUSIONNAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.
Cite this article as: [1]Hu Huabin, Zhang Jianwei, Li Yunfeng, et al.Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial[J].JOURNAL OF CLINICAL ONCOLOGY,2024,42(25).
LncRNAs serve as novel biomarkers for diagnosis and prognosis of childhood ALL
长链非编码RNA（LncRNAs）可作为儿童急性淋巴细胞白血病（ALL）诊断和预后的新型生物标志物
Issue BIOMARKER RESEARCH 2021, Volume 9 Issue 1
期刊：《生物标志物研究》2021年，第9卷第1期
Author Huang Xuanmei / Huang Libin / Xie Qing / Zhang Ling / Huang Shaohui / Hong Mingye / Li Jiangbin / Huang Zunnan / Zhang Hua
Keywords LncRNAs / Childhood acute lymphoblastic leukemia / Leukemia-free survival / Proliferation / Apoptosis
Abstract
Background Although some studies have demonstrated that lncRNAs are dysregulated in hematopoietic malignancies and may regulate the progression of leukemia, the detailed mechanism underlying tumorigenesis is still unclear. This study aimed to investigate lncRNAs that are differentially expressed in childhood B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) and their potential roles in the progression of childhood ALL. Methods Microarrays were used to detect differentially expressed lncRNAs and mRNAs. Several aberrantly expressed lncRNAs were validated by qRT-PCR. Leukemia-free survival was analyzed using the Kaplan-Meier method with a log-rank test. The co-expression correlations of lncRNAs and mRNAs were determined by Spearman's correlation coefficient. CCK-8 assays and flow cytometry were performed to measure cell proliferation and apoptosis. Results We revealed that many lncRNAs were abnormally expressed in B-ALL and T-ALL. LncRNA/mRNA co-expression and the gene locus network showed that dysregulated lncRNAs are involved in diverse cellular processes. We also assessed the diagnostic value of the differentially expressed lncRNAs and confirmed the optimal combination of TCONS_00026679, uc002ubt.1, ENST00000411904, and ENST00000547644 with an area under the curve of 0.9686 [95 % CI: 0.9369-1.000, P < 0.001], with 90.7 % sensitivity and 92.19 % specificity, at a cut-off point of -0.5700 to distinguish childhood B-ALL patients from T-ALL patients, implying that these specific lncRNAs may have potential to detect subsets of childhood ALL. Notably, we found that the 8-year leukemia-free survival of patients with high TCONS_00026679 (p = 0.0081), ENST00000522339 (p = 0.0484), ENST00000499583 (p = 0.0381), ENST00000457217 (p = 0.0464), and ENST00000451368 (p = 0.0298) expression levels was significantly higher than that of patients with low expression levels of these lncRNAs, while patients with high uc002ubt.1 (p = 0.0499) and ENST00000547644 (p = 0.0451) expression levels exhibited markedly shorter 8-year leukemia-free survival. In addition, some lncRNAs were found to play different roles in cell proliferation and apoptosis in T-ALL and B-ALL. Conclusions Dysregulated lncRNAs involved in different regulatory mechanisms underlying the progression of childhood T-ALL and B-ALL might serve as novel biomarkers to distinguish ALL subsets and indicate poor outcomes.
Cite this article as: [1]Huang Xuanmei, Huang Libin, Xie Qing, et al.LncRNAs serve as novel biomarkers for diagnosis and prognosis of childhood ALL[J].BIOMARKER RESEARCH,2021,9(1).
胞外赖氨酸乙酰化介导的白血病抑制因子受体同源二聚化通过PDPK1/AKT/GCN5轴促进前列腺癌进展
Issue CLINICAL AND TRANSLATIONAL MEDICINE 2022, Volume 12 Issue 2
期刊：《临床转化医学》2022年，第12卷第2期
Author Dine Yufeng / Chi Honggang / Shao Jialiang / Sh Tiezhu / Yu Hua / Wan Xiang / Wang Xiongjun
Abstract
Background Prostate cancer (PCa), an inert tumour, has a long progression period, but valid biomarkers and methods for effectively and sensitively monitoring PCa progression are lacking, prompting us to identify new predictors for diagnosis and prognosis. Posttranslational modifications characterizing receptor activation are considered potentially strong indicators of disease progression. Methods The posttranscriptional regulation of leukaemia inhibitory factor receptor (LIFR) and its novel downstream signalling activity in PCa were studied using liquid mass spectrometry, genetically engineered mouse (GEM) models, organoid assays, lentivirus packaging, infection and stable cell line construction. Results In this study, the level of acetylated K620 on LIFR in its extracellular domain was shown to predict the progression and prognosis of PCa. In PCa cells, LIFR-K620 acetylation is reversibly mediated by GCN5 and SIRT2. GEM experiments and organoid assays confirmed that the loss of LIFR-K620 acetylation inhibits PCa progression. Mechanistically, K620 acetylation facilitates LIFR homodimerization and subsequently promotes LIFR-S1044 phosphorylation and activation, which further recruits PDPK1 to activate AKT signalling and sequentially enhances the GCN5 protein level to sustain the protumour level of LIFR-K620 acetylation by preventing GCN5 degradation via CRL4(Cdt2) E3 ligase. Conclusions Acetylation of extracellular K620 on LIFR reinforces its homodimerization and integrates the activities of PDPK1, AKT, GSK3 beta and GCN5 to form a novel positive feedback loop in PCa; this modification is thus a promising biomarker for monitoring PCa progression.
Cite this article as: [1]Dine Yufeng, Chi Honggang, Shao Jialiang, et al.Leukemia inhibitory factor receptor homodimerization mediated by acetylation of extracellular lysine promotes prostate cancer progression through the PDPK1/AKT/GCN5 axis[J].CLINICAL AND TRANSLATIONAL MEDICINE,2022,12(2).
伴随基因改变与肺腺癌患者表皮生长因子受体（EGFR）靶向治疗反应相关
Issue TRANSLATIONAL LUNG CANCER RESEARCH 2020, Volume 9 Issue 4 1225-1234
期刊：《转化肺癌研究》2020年，第9卷第4期，1225-1234 页
Author Chen Hualin / Liu Meilian / Dai Zhiwei / Li Shujun / Luo Yiping / Wang Yongcun / Su Wenmei / Cai Weijing / Yang Donghong / Huang Jian / Yang Zhixiong
Keywords Non-small cell lung cancer (NSCLC) / concomitant genetic alteration / next generation sequencing (NGS) / epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) / response
Abstract
Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are considered to be more effective than chemotherapy in the treatment of EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, in addition to EGFR-sensitive mutations, the genetic factors that affect the prognosis of patients who receive TKI treatment are not yet clear. Methods: The clinical data of 36 NSCLC patients with EGFR mutation who received TKI treatment were retrospectively analyzed. Liquid re-biopsy with next generation sequencing (NGS) analysis was performed to analyze genetic alterations and potential resistance mechanisms. Results: All of the patients harbored actionable sensitive EGFR mutations by NGS, with the major types being 19del or 21L858R (52.78%, 19/36 and 55.56%, 20/36, respectively). The 3 most frequent accompanying somatic mutations were TP53 (12, 48.4%), KRAS (7, 19.44%) and PIK3CA (3, 8.33%). Concomitant mutations were present in 16 patients (44.44%). The occurrence of co-mutation was found to be significantly related to a history of smoking [87.5% (7 of 8) vs. 32.14% (9 of 28); Pearson chi-square, P=0.005]. Patients who received EGFR-TKIs treatment (P=0.0079) or third-generation EGFR-TKIs only (P=0.0468) had better progression-free survival (PFS). Concomitant mutations were significantly related to lower objective response rates (43.75% vs. 80.0%; P=0.024) and poorer PFS (P<0.001). Patients with concomitant genetic alterations had a worse response after receiving EGFR-TKIs treatment (P=0.0033). Conclusions: Our research underscores the importance of using multiple molecular profiles. Concomitant genetic alterations were significantly associated with response to EGFR targeted therapy in NSCLC. Therefore, research on multi-drug or sequential therapy to address the covariation that drives drug resistance is urgently needed.
Cite this article as: [1]Chen Hualin, Liu Meilian, Dai Zhiwei, et al.Concomitant genetic alterations are associated with response to EGFR targeted therapy in patients with lung adenocarcinoma[J].TRANSLATIONAL LUNG CANCER RESEARCH,2020,9(4):1225-1234.
The role of ncRNAs in neuroblastoma: mechanisms, biomarkers and therapeutic targets
非编码RNA（ncRNAs）在神经母细胞瘤中的作用：机制、生物标志物与治疗靶点
Issue BIOMARKER RESEARCH 2022, Volume 10 Issue 1
期刊：《生物标志物研究》2022年，第10卷第1期
Author Huang Shaohui / Gong Naying / Li Jiangbin / Hong Mingye / Li Li / Zhang Ling / Zhang Hua
Keywords Neuroblastoma / ncRNAs / Biomarkers / Therapeutic targets
Abstract
Neuroblastoma (NB) is a malignant tumor in young children that originates from the neural crest of the sympathetic nervous system. Generally, NB occurs in the adrenal glands, but it can also affect the nerve tissues of the neck, chest, abdomen, and pelvis. Understanding the pathophysiology of NB and developing novel therapeutic approaches are critical. Noncoding RNAs (ncRNAs) are associated with crucial aspects of pathology, metastasis and drug resistance in NB. Here, we summarized the pretranscriptional, transcriptional and posttranscriptional regulatory mechanisms of ncRNAs involved in NB, especially focusing on regulatory pathways. Furthermore, ncRNAs with the potential to serve as biomarkers for risk stratification, drug resistance and therapeutic targets are also discussed, highlighting the clinical application of ncRNAs in NB.
Cite this article as: [1]Huang Shaohui, Gong Naying, Li Jiangbin, et al.The role of ncRNAs in neuroblastoma: mechanisms, biomarkers and therapeutic targets[J].BIOMARKER RESEARCH,2022,10(1).
自然杀伤细胞：凭借免疫效能、基因工程与纳米技术引领癌症免疫治疗
Issue CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY 2023, Volume 193
期刊：《肿瘤学与血液学评论》2023年，第193卷
Author Pan Weiyi / Tao Tao / Qiu Yishu / Zhu Xiao / Zhou Xiaorong
Keywords CAR-engineered NK cells / Drug development / Immune checkpoint inhibitors / Immune function / Nanotechnology-treated NK cells / Tumor immunotherapy
Abstract
Natural killer (NK) cells are vital components of the human immune system, acting as innate lymphocytes and playing a crucial role in immune surveillance. Their unique ability to independently eliminate target cells without antigen contact or antibodies has sparked interest in immunological research. This review examines recent NK cell developments and applications, encompassing immune functions, interactions with target cells, genetic engineering techniques, pharmaceutical interventions, and implications in cancers. Insights into NK cell regulation emerge, with a focus on promising genetic engineering like CAR-engineered NK cells, enhancing specificity against tumors. Immune checkpoint inhibitors also enhance NK cells' potential in cancer therapy. Nanotechnology's emergence as a tool for targeted drug delivery to improve NK cell therapies is explored. In conclusion, NK cells are pivotal in immunity, holding exciting potential in cancer immunotherapy. Ongoing research promises novel therapeutic strategies, advancing immunotherapy and medical interventions.
Cite this article as: [1]Pan Weiyi, Tao Tao, Qiu Yishu, et al.Natural killer cells at the forefront of cancer immunotherapy with immune potency, genetic engineering, and nanotechnology[J].CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY,2023,193.
基于跨域迁移学习挖掘稳健影像特征，鉴别孤立性肺肉芽肿结节与实性肺腺癌
Issue CANCERS 2023, Volume 15 Issue 3
期刊：《癌症》2023年，第15卷第3期
Author Feng Bao / Chen Xiangmeng / Chen Yehang / Yu Tianyou / Duan Xiaobei / Liu Kunfeng / Li Kunwei / Liu Zaiyi / Lin Huan / Li Sheng / Chen Xiaodong / Ke Yuting / Li Zhi / Cui Enming / Long Wansheng / Liu Xueguo
Keywords lung granulomatous nodule / lung adenocarcinoma / solitary pulmonary solid nodules / adaptive cross-domain transfer learning / whole slide image
Abstract
Simple Summary This retrospective study aimed to find suitable source domain data in cross-domain transfer learning to extract robust image features and build a model to preoperatively distinguish LGN from LAC in SPSNs. The experiment showed that, compared with other source domains (such as ImageNet and LIDC), the transfer learning signature based on lung whole slide images as the source domain could extract more robust features (Wasserstein distance: 1.7108). Finally, a cross-domain transfer learning radiomics model combining transfer learning signatures based on lung whole slide images as the source domain, clinical factors and subjective CT findings was constructed. According to the validation cohort results of five centres (AUC range: 0.9074-0.9442), the cross-domain transfer learning radiomics model that combined multimodal data could assist physicians in preoperatively differentiating LGN from LAC in SPSNs. Purpose: This study aimed to find suitable source domain data in cross-domain transfer learning to extract robust image features. Then, a model was built to preoperatively distinguish lung granulomatous nodules (LGNs) from lung adenocarcinoma (LAC) in solitary pulmonary solid nodules (SPSNs). Methods: Data from 841 patients with SPSNs from five centres were collected retrospectively. First, adaptive cross-domain transfer learning was used to construct transfer learning signatures (TLS) under different source domain data and conduct a comparative analysis. The Wasserstein distance was used to assess the similarity between the source domain and target domain data in cross-domain transfer learning. Second, a cross-domain transfer learning radiomics model (TLRM) combining the best performing TLS, clinical factors and subjective CT findings was constructed. Finally, the performance of the model was validated through multicentre validation cohorts. Results: Relative to other source domain data, TLS based on lung whole slide images as source domain data (TLS-LW) had the best performance in all validation cohorts (AUC range: 0.8228-0.8984). Meanwhile, the Wasserstein distance of TLS-LW was 1.7108, which was minimal. Finally, TLS-LW, age, spiculated sign and lobulated shape were used to build the TLRM. In all validation cohorts, The AUC ranges were 0.9074-0.9442. Compared with other models, decision curve analysis and integrated discrimination improvement showed that TLRM had better performance. Conclusions: The TLRM could assist physicians in preoperatively differentiating LGN from LAC in SPSNs. Furthermore, compared with other images, cross-domain transfer learning can extract robust image features when using lung whole slide images as source domain data and has a better effect.
Cite this article as: [1]Feng Bao, Chen Xiangmeng, Chen Yehang, et al.Identifying Solitary Granulomatous Nodules from Solid Lung Adenocarcinoma: Exploring Robust Image Features with Cross-Domain Transfer Learning[J].CANCERS,2023,15(3).
临床显著性门静脉高压症（CSPH）对早期肝细胞癌（HCC）肝切除术后患者的影响
Issue EJSO 2023, Volume 49 Issue 4 771-779
期刊：《欧洲外科肿瘤杂志》（EJSO）2023年，第49卷第4期，771-779页
Author Xia Feng / Huang Zhiyuan / Zhang Qiao / Ndhlovu Elijah / Chen Xiaoping / Zhang Bixiang / Zhu Peng
Keywords Hepatocellular carcinoma / Portal hypertension / BCLC stage / Prognosis
Abstract
Background and aim: The impact of currently clinically significant portal hypertension (CSPH) for pa-tients with early-stage HCC after surgery remains controversial. The purpose of this study is to under-stand the specific effect of CSPH on patients with early-stage (BCLC A stage) HCC after surgery.Methods: We collected data from 386 HCC patients treated at two centers from December 2009 to January 2017.224 patients (all treated by hepatectomy) were in BCLC stage A, of which, 122 had no CSPH, and 102 had CSPH. There were 162 patients in BCLC stage B (who underwent surgery, TACE, and con-servative treatment). The prognosis of the CSPH and non-CSPH groups in BCLC stage A was compared using the Kaplan-Meier method. We used multivariate Cox regression to analyze prognostic factors in patients in BCLC stage A and compared the prognosis of the two groups with the BCLC stage B group.Results: Among the 224 BCLC stage A patients after surgery, the overall survival (OS) and recurrence-free survival (RFS) of the CSPH group were worse than those of the non-CSPH group (P < 0.001, HR = 2.340 [1.554-3.523]; P < 0.001, HR = 2.577[1.676-3.812]) The multivariate Cox proportional hazards model indicated that CSPH was an independent prognostic factor for OS and RFS in BCLC stage A patients. BCLC stage A patients with CSPH treated by hepatectomy had a comparable prognosis to BCLC B stage patients (P = 0.378), and the OS and RFS (P = 0.229; P = 0.077) in the CSPH (BCLC A) group were also comparable to BCLC stage B patients treated with surgery alone.Conclusions: CSPH can affect the surgical prognosis of early-stage (BCLC stage A) HCC. BCLC stage A patients with CSPH have a prognosis comparable to patients with BCLC stage B. An additional stage, such as the BCLC stage A-B, can be considered.(c) 2022 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
Cite this article as: [1]Xia Feng, Huang Zhiyuan, Zhang Qiao, et al.Clinically significant portal hypertension (CSPH) on early-stage HCC following hepatectomy: What's the impact?[J].EJSO,2023,49(4):771-779.
基于基因表达特征预测成人T细胞淋巴母细胞淋巴瘤（T-LBL）患者的生存期：一项多中心研究
Issue LEUKEMIA 2020, Volume 34 Issue 9 2392-2404
期刊：《白血病》（LEUKEMIA）2020年，第34卷第9期，2392-2404页
Author Tian Xiao-Peng / Xie Dan / Huang Wei-Juan / Ma Shu-Yun / Wang Liang / Liu Yan-Hui / Zhang Xi / Huang Hui-Qiang / Lin Tong-Yu / Rao Hui-Lan / Li Mei / Liu Fang / Zhang Fen / Zhong Li-Ye / Liang Li / Lan Xiao-Liang / Li Juan / Liao Bing / Li Zhi-Hua / Tang Qiong-Lan / Liang Qiong / Shao Chun-Kui / Zhai Qiong-Li / Cheng Run-Fen / Sun Qi / Ru Kun / Gu Xia / Lin Xi-Na / Yi Kun / Shuang Yue-Rong / Chen Xiao-Dong / Dong Wei / Sang Wei / Sun Cai / Liu Hui / Zhu Zhi-Gang / Rao Jun / Guo Qiao-Nan / Zhou Ying / Meng Xiang-Ling / Zhu Yong / Hu Chang-Lu / Jiang Yi-Rong / Zhang Ying / Gao Hong-Yi / He Wen-Jun / Xia Zhong-Jun / Pan Xue-Yi / Lan Hai / Li Guo-Wei / Liu Lu / Bao Hui-Zheng / Song Li-Yan / Kang Tie-Bang / Cai Qing-Qing
Abstract
We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p < 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p < 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p < 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score >= 154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.
Cite this article as: [1]Tian Xiao-Peng, Xie Dan, Huang Wei-Juan, et al.A gene-expression-based signature predicts survival in adults with T-cell lymphoblastic lymphoma: a multicenter study[J].LEUKEMIA,2020,34(9):2392-2404.
