Non-histone acetylation regulates protein stability, transcription, and immune signaling, yet its substrate-specific roles in colon adenocarcinoma (COAD) remain unclear. We performed an integrative multi-omics analysis to characterize acetylation substrate-related transcriptional signatures and their clinical relevance. Expression patterns and prognostic impacts of 33 acetylation-related enzymes were evaluated pan-cancer, and substrate-related networks were computationally inferred. A 15-gene substrate expression-based acetylation substrate-related imbalance score (AIScore) stratified COAD patients into prognostically distinct groups. Single-cell RNA sequencing and spatial transcriptomics revealed AIScore-high malignant cells preferentially interacting with SPP1-positive macrophages, forming immunosuppressive niches with reduced predicted immunotherapy response. Exploratory deep learning-based pathomics of whole-slide images, including ResNet-50 feature extraction, PCA, clustering, and Grad-CAM visualization, highlighted AIScore-associated morphologic hotspots at tumor-immune interfaces. These findings indicate that non-histone acetylation substrate-related transcriptional programs in COAD are linked to poor prognosis and spatial immune heterogeneity, while pathomics provides supportive morphology-linked evidence requiring further validation.

Cisplatin resistance is a major therapeutic challenge in esophageal squamous cell carcinoma (ESCC). circRNAs play an important role in cisplatin resistance. The aim of this paper was to investigate the role and mechanism of hsa_circ_0049271 in ESCC progression and drug resistance. GEO database was retrieved to collect circRNAs, miRNAs, and mRNAs associated with cisplatin resistance in ESCC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect hsa_circ_0049271 expression levels in ESCC cell lines. CCK-8 assay, flow cytometric assay, and cell migration/invasion assays were used to examine the function of hsa_circ_0049271 in ESCC cells. RT-qPCR and coculture assays were used to detect the effect of circRNA_103615 on cellular senescence under cisplatin treatment. Hsa_circ_0049271, miR-455-5p, and ETS1 were dysregulated in ESCC tissues. ESCC cell lines had increased levels of hsa_circ_0049271 and ETS1 mRNA compared with normal cells and normal tissues, as well as decreased levels of miR-455-5p. Functionally, small interfering RNA silencing of hsa_circ_0049271 by small interfering RNA resulted in suppression of cell growth, migration, and invasion in both non-senescent and senescent cells. MiR-455-5p was significantly increased, but ETS1 expression was significantly decreased after hsa_circ_0049271 knockdown. Hsa_circ_0049271 promoted the secretion of senescence-associated secretory phenotypes, including IL1B, IL6, CXCL5, and MMP3. Hsa_circ_0049271 may enhance DDP treatment-induced cellular senescence to promote ESCC progression and chemoresistance through the miR-455-5p/ETS1 axis.

Background:Neoadjuvant concurrent chemoradiotherapy (CCRT) has become the preferred modality for patients with inoperable locally advanced esophageal squamous cell carcinoma (ESCC). To investigate whether the CCRT regimen of paclitaxel plus 5-fluorouracil (TF) increases the efficacy when compared with a regimen of cisplatin plus 5-fluorouracil (PF) in the locally advanced ESCC patient treatment. Methods:A total of 103 ESCC patients were randomly divided into study group (TF, n=52) and control group (PF, n=51), treated in Affiliated Hospital of Jiangnan University from July 2014 to June 2016. These patients were followed up for 2 years in our department by performing certain examinations to evaluate their survival state. The primary endpoint was overall survival (OS). Local control (LC), progression-free survival (PFS) and adverse effects were secondary endpoints. Results:A total of 103 patients were enrolled. The 1-, 2-year OS for TF group was 76.9%, 59.6% versus 74.5% (χ2=0.134, P=0.72), 56.9% (χ2=0.151, P=0.70) for PF group. The 1-, 2-year LPS for TF group and PF group were 71.2%, 61.5% and 66.7% (χ2=0.065, P=0.80), 58.8% (χ2=0.079, P=0.78) respectively. The serious leukopenia (grade 3-4) incidence rate for TF group was 36.5% versus 17.6% for PF group (χ2=4.642, P<0.05). Conclusions:When compared with the PF regimen, the TF regimen shows no survival benefit but exhibited a trend to a better control rate and a decreased distant metastasis rate. Both regimens showed tolerable toxicity. Trial Registration:Chinese Clinical Trial Registry ChiCTR2500100712.

Objective:To build a predictive model for symptomatic radiation pneumonitis(RP) using the pretreatment CT radiomics features, clinical and dosimetric data of lung cancer patients by using machine learning method.Methods:A retrospective analysis of 103 lung cancer patients who underwent radiotherapy in the Affiliated Hospital of Jiangnan University from November 2018 to April 2020 was performed. Total normal lung tissues were segmented as an interested volume in pretreatment CT images, and then 250 radiomics features were extracted. The correlations of RP and clinical or dosimetric features were firstly investigated with univariate analysis. Then all clinical data, dosimetric data and CT radiomics features were collected and considered as predictors for modeling of RP grade ≥ 2. Features were selected through LASSO machine learning method, and the predictive model was built. Finally, nomogram for risk of RP were obtained according to the selected features.Results:The result of univariate analysis showed that symptomatic RP was significantly correlated with lung dosimetric parameters including mean lung dose (MLD), V20 Gy and V30 Gy( t=2.20, 2.34 and 2.93, P<0.05). Four features, including lung dose volume percentage V30 Gyand three radiomics features, entropy feature of GLCM, mean and median feature of wavelet histogram were selected among all clinical, dosimetric features and radiomics features. AUC of the predicted model obtained from selected features reached 0.757. For convenient clinical use, the nomogram were obtained, and then personalized RP risk prediction and early intervention could be performed according to this nomogram. Conclusions:Pretreatment CT radiomics and dosimetric features can be used in predicting symptomatic RP, which will be useful for advanced intervention treatment.

Objective:To explore the efficacy of elective nodal irradiation (ENI) and involved field irradiation (IFI) combined with chemotherapy in treatment of esophageal cancer.Methods:A total of 104 patients with esophageal cancer in Affiliated Hospital of Jiangnan University from May 2018 to May 2020 were selected as subjects for prospective study. All patients were randomly divided into observation group and control group by lottery method with 52 cases in each group. The target volume of observation group was delineated with IFI, and the control group was delineated with ENI. The curative effects, the levels of serum tumor markers [carbohydrate antigen 50 (CA50), squamous cell carcinoma (SCC) and carcinoembryonic antigen (CEA)] before and after treatment, the 1-year overall survival (OS) rate, the incidence of adverse reactions and the scores of various dimensions of health survey summary (SF-36) after treatment were compared between the two groups.Results:The total effective rate in the observation group was 90.38% (47/52), the total effective rate in the control group was 84.62% (44/52), and the difference was not statistically significant ( χ2 = 0.79, P =0.374). There was no statistical difference in CA50, CEA, SCC levels between the two groups before and after treatment (all P > 0.05). After treatment, the CA50, CEA and SCC levels in the two groups were lower than those before treatment, and the differences were statistically significant (all P < 0.05). The 1-year OS rate of the observation group was 94.23%, the control group was 90.38%, and the difference in OS between the two groups was not statistically significant ( χ2 = 0.54, P = 0.462). The incidence of acute radiation esophagitis in the observation group was lower than that in the control group, and the difference was statistically significant ( P < 0.001). There was no statistical difference between the two groups in SF-36 scale scores of physical functioning, role-physical, bodily pain, mental health, vitality, social functioning, role-emotional, and general health after treatment (all P > 0.05). Conclusions:Both ENI and IFI are effective treatments for patients with esophageal cancer. There is no significant difference in the quality of life of patients between the two delineation methods, but the incidence of acute radiation esophagitis is lower in patients with IFI regimen.

目的 探讨重组人白细胞介素2(rhIL-2)联合重组人粒细胞-巨噬细胞刺激因子(rhGM-CSF)治疗食管癌放疗后放射性食管炎的临床效果.方法 选择食管癌放疗后放射性食管炎患者106例,随机分为观察组、对照组各53例.对照组予rhIL-2100万U静脉滴注,每天1次;观察组在对照组基础上予rhGM-CSF 100μg皮下注射,每周3次.两组均连续治疗14 d.比较两组治疗前后放射性食管炎分级、外周血T淋巴细胞亚群(CD3+、CD4+、CD8+T细胞及CD4+/CD8+)和自然杀伤细胞(CD16+CD56+NK细胞)以及生活质量核心问卷-30(QLQ-C30)评分(包括躯体功能、角色功能、情绪功能、认知功能和社会功能五个维度).结果 观察组治疗后放射性食管炎分级0、Ⅰ级占比显著高于本组治疗前和对照组治疗后,而放射性食管炎分级Ⅱ～Ⅳ级占比显著低于本组治疗前和对照组治疗后(P均<0.05).两组治疗后CD3+、CD4+T细胞及CD4+/CD8+和CD16+CD56+NK细胞均高于治疗前,而CD8+T细胞均低于治疗前,以观察组治疗后上述指标变化更明显(P均<0.05).两组治疗后躯体功能、角色功能、情绪功能、认知功能和社会功能评分均高于治疗前,以观察组治疗后上述评分变化更明显(P均<0.05).结论 rhIL-2联合rhGM-CSF能够降低食管癌放疗后放射性食管炎严重程度,提高机体免疫功能,改善患者生活质量.

Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment, which are characterized by pro-tumor M2 phenotype and correlate with poor survival of nasopharyngeal carcinoma (NPC). Heme oxygenase-1 (HO-1) plays a crucial role in macrophage polarization toward M2 phenotype, but its prognosis significance in NPC has been rarely determined. To gain insights into the HO-1 expression profile and to determine the clinical significance of HO-1 in NPC, we performed immunohistochemistry analyses in 126 NPC specimens. CD163, a highly specific marker of M2 macrophages, was used as a surrogate for the polarization state of TAMs. Our results showed that high expression of HO-1 and CD163 were detected in TAMs for 57.9% (73/126) and 61.9% (78/126) of the studied patients, and both of them were significantly associated with worse survival. Additionally, a significant correlation between the intensities of HO-1 and CD163 was identified, and HO-1 exhibited a superior ability in predicting survival compared with CD163. Our study revealed for the first time that overexpression of HO-1 characterized a poor-prognosis subtype in NPC. Individualized therapy targeting HO-1 might serve as a promising treatment modality for NPC.

Real-time assessment of therapeutic response in patients with advanced lung cancer presents a major challenge throughout the treatment process. Currently, computed tomography imaging is often used; however, it is radiation-based and hysteretic and is not suitable for repeated use as a real-time assessment. Blood biomarkers represent a novel solution for assessing therapeutic response in patients with advanced lung cancer. In the present study, the efficacy of a methylation marker [methylated prostaglandin E receptor 4 (mPTGER4)] and four protein markers [carcinoma antigen 125 (CA125), carcinoembryonic antigen (CEA), cytokeratin 19-fragments (cyfra21-1) and neuron-specific enolase (NSE)] were simultaneously evaluated to determine their potential in facilitating therapeutic response monitoring as well as their prognostic values in patients with stage IV lung cancer. The results indicated that, following treatment, the blood levels of methylated PTGER4 and NSE had significantly decreased, and mPRGER4, CA125, CEA and NSE exhibited a significant decrease in percentage level. Since mPTGER4 exhibited a higher rate of positive detection prior to therapy, and a greater response of sensitivity to therapy compared to the protein markers, it may represent an improved marker for the monitoring of therapeutic response. The efficacy of the markers in predicting the overall survival (OS) rate of patients with stage IV lung cancer was also assessed. Results from the follow-up of patients (up to 891 days) revealed that the blood levels of mPTGER4, CA125 and NSE before treatment were able to predict overall survival (OS) rate. Additionally, the percentage change in expression levels of CA125, CEA and NSE was also able to predict the OS rate. In conclusion, the present results indicate that mPTGER4 represents an improved biomarker for monitoring therapeutic efficacy compared with CA125, CEA, Cyfra21-1 and NSE. In predicting the long-term survival of patients with stage IV lung cancer; however, the pre-treatment levels of mPTGER4, CA125 and NSE and the percentage changes of CA125, CEA and NSE may be used as the markers.

Objective To compare the efficacy and safety of two concurrent chemoradiotherapy regimens between paclitaxel plus fluorouracil( TF) and cisplatin plus fluorouracil ( PF) in the treatment of locally advanced esophageal squamous carcinoma. Methods 103 patients with locally advanced esophagus carcinoma were treated in Affiliated Hospital of Jiangnan University from December 2014 to February 2016, and randomly assigned to either study group ( TF ) or control group ( PF ) according to random number table, of which 52 patients in the TF group while 51 patients in the PF group. The primary outcome was overall survival(OS), and secondary outcomes include progression-free survival(PFS), local progression-free survival( LPFS) and side effects. Results The 1-year OS for TF group was 76. 9％ versus 74. 5％ for PF group( P>0. 05 ) , and the 2-year OS for TF group was 59. 6％ versus 56. 9％ for PF group ( P >0. 05). The 1-year LPFS for TF group and PF group were 71. 2％ and 66. 7％ respectively(P>0. 05), and the 2-year LPFS for TF group and PF group were 61. 5％ and 58. 8％ respectively(P>0. 05). The 1-year PFS for TF group was 63. 5％ versus 62. 7％ for PF group ( P>0. 05 ) , and the 2-year PFS for TF group was 51. 9％ versus 39. 2％ for PF group ( P>0. 05 ) . The incidence rate of serious ( grade 3- 4 ) leukopenia for TF group was 36. 5％ versus 17. 6％ for PF group(χ2 =4. 642, P<0. 05). The incidence rate of serious (grade 3-4) acute radiation pneumonitis was 15. 4％ in the TF group, higher than that in the PF group with the rate of 3. 9％(χ2 =3. 859, P<0. 05), while the incidence rate of severe nausea and vomiting for PF group was 17. 6％ versus 1. 9％ for TF group(χ2 =7. 262, P <0. 05). The difference between the two groups was statistically significant. Conclusions Patients who were treated with two concurrent chemoradiotherapy regimens showed no difference in OS, PFS and LPFS. The regimen on the basis of Paclitaxel has higher risk of adverse effects incidence rates of hematological toxicity and acute radiation pneumonitis, while digestive system toxicity must be concerned when concurrent chemoradiotherapy is performed on the basis of cisplatin plus fluorouracil.

目的 比较紫杉醇联合氟尿嘧啶(TF)放化疗与顺铂联合氟尿嘧啶(PF)放化疗两种方案在食管癌放射治疗中发生的不良反应.方法 选择江南大学附属医院自2014年10月—2017年2月所收治的103例患者,随机分成TF组及PF组,TF组患者在放疗期间同步使用紫杉醇联合氟尿嘧啶化疗,PF组则使用顺铂联合氟尿嘧啶化疗,观察比较两组治疗期间及治疗后发生的不良反应.结果 TF组3、4级白细胞减低率为36.5％,3、4级急性放射性肺炎发生率为15.4％,高于PF组(分别为17.6％,3.9％),PF组3、4级呕吐反应率17.6％,为高于TF组的1.9％,差异有统计学意义(P<0.05).结论 食管癌患者采用紫杉醇联合氟尿嘧啶同期放化疗时,血液学毒性及放射性肺炎发生率相对较高,治疗期间需加强预防与对症治疗,而使用顺铂联合方案治疗时,需关注呕吐等消化系统不良反应.

Objective: In this study, we compared the effects of combination of celecoxib, intensity-modulated radiation therapy (IMRT) and hippocampal sparing, IMRT with hippocampal sparing and IMRT only on cognitive function, life quality and therapeutic effects in patients with nasopharyngeal carcinoma (NPC). Methods: From June 2015 to December 2016, 177 cases with NPC in our hospital were finally enrolled and randomly divided into three groups: IMRT only group (I group), hippocampal sparing IMRT (H group) and celecoxib combined with hippocampal sparing IMRT group (Ce group). Cognitive function and life quality were evaluated three months after treatment via Mini-Mental State Examination (MMSE) and Quality of life questionnaire (QLQ C30) respectively. Indicators for therapeutic effects including complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD), adverse reactions, recurrence and metastasis of tumor and serum tumor marker carcinoembryonic antigen (CEA) level of patients were also compared. Results: Before the intervention, there was no difference in cognitive function score among all the patients (P = 0.876). After the treatment, no significant difference was found for RR among groups (P = 0.245), however, patients in the Ce group showed the highest cognitive function score (P < 0.001); the differences in adverse reactions including dry mouth (P = 0.026, Ce vs. H; P = 0.000, Ce vs. I; P = 0.000, H vs. I), oral mucositis (P = 0.060, Ce vs. H; P = 0.008, Ce vs. I; P = 0.396, H vs. I), skin reaction (P = 0.654, Ce vs. H; P = 0.027, Ce vs. I; P = 0.065, H vs. I), irradiation otitis media (P = 0.097, Ce vs. H; P = 0.009, Ce vs. I; P = 0.051, H vs. I) had statistical significance, and their incidence rates in Ce group were lowest. Meanwhile, recurrence and metastasis were less in the Ce group although the differences were insignificant (P = 0.302 and 0.638). The serum level of CEA was notably lower in Ce group (P = 0.031, Ce vs. H; P = 0.020, Ce vs. I; P = 0.512, H vs. I). Life quality scores about cognitive function and role function of H group and Ce group were higher than that of I group while Ce group was the highest (Cognitive function: P = 0.020, Ce vs. H; P = 0.015, Ce vs. I and P = 0.023, H vs. I; role function: P = 0.039, Ce vs. H; P = 0.011, Ce vs. I and P = 0.031, H vs. I). Conclusion: Celecoxib combined with hippocampus sparing IMRT for the treatment of NPC patients could drastically alleviate cognitive dysfunction, improve life quality and reduce the occurrence of adverse events compared with hippocampal sparing IMRT and IMRT only.