Personalized analysis of human cancer multi-omics for precision oncology.

Multi-omics technologies, encompassing genomics, proteomics, and transcriptomics, provide profound insights into cancer biology. A fundamental computational approach for analyzing multi-omics data is differential analysis, which identifies molecular distinctions between cancerous and normal tissues. Traditional methods, however, often fail to address the distinct heterogeneity of individual tumors, thereby neglecting crucial patient-specific molecular traits. This shortcoming underscores the necessity for tailored differential analysis algorithms, which focus on particular patient variations. Such approaches offer a more nuanced understanding of cancer biology and are instrumental in pinpointing personalized therapeutic strategies. In this review, we summarize the principles of current individualized techniques. We also review their efficacy in analyzing cancer multi-omics data and discuss their potential applications in clinical practice.

A dual-targeted Gd-based contrast agent for magnetic resonance imaging in tumor diagnosis.

Enhanced magnetic resonance imaging (MRI) has important clinical value in the diagnosis of tumors. Much effort has been made to improve the relaxivity and specificity of contrast agents (CAs) in tumor diagnosis over the past few decades. However, there is still a lack of CAs which not only enhance the signal intensity of tumors rather than surrounding tissues in MRI but also maintain a high signal intensity prolonged for a long time. Herein, we synthesized a dual-targeted CA, RGD-(DOTA-Gd)-TPP (RDP), in which RGD is used to target the αvß3 integrin receptor overexpressed in tumor cells and TPP is used to bind to a mitochondrion further. The structure of RDP was characterized and its properties, such as relaxivity and biosafety, were measured and in vitro and in vivo MRI assays were carried out. It has been proven that RDP has higher relaxivity of aqueous solution than Magnevist used in clinics. Moreover, RDP achieved higher signal intensity and a longer signal duration in tumor imaging. Therefore, RDP can be applied as the potential dual-targeted MRI CA for clinical tumor diagnosis.

Hesperetin promotes bladder cancer cells death via the PI3K/AKT pathway by network pharmacology and molecular docking.

Patients with bladder cancer (BLCA) still show high recurrence after surgery and chemotherapy. Hesperetin (HE), as a natural compound, has attracted researchers' attention due to its low toxicity and easy access. However, the inhibitory effect of HE on BLCA remains unknown. The hub genes and enrichment pathways regulated by HE in the treatment of BLCA were predicted by network pharmacology. The molecular docking of HE and hub proteins was visualized. Colony and CCK8 assays were used to test cell proliferation, and BLCA migration was confirmed by transwell and wound healing assays. In addition, the occurrence of apoptosis and ferroptosis was demonstrated by Hoechst staining, transmission electron microscopy (TEM) and ROS (reactive oxygen species) assay. Western Blotting was performed to validate the hub proteins, target functions and pathways. SRC, PIK3R1 and MAPK1 were identified as hub targets for HE in BLCA, involving the PI3k/AKT pathway. Furthermore, HE inhibited the proliferation and migration of BLCA cells. The MMP2/MMP9 proteins were significantly inhibited by HE. The increased expression of Bax and cleaved caspase-3 indicated that HE could promote BLCA cell apoptosis. In addition, Hoechst staining revealed concentrated and illuminated apoptotic nuclei. The activation of ROS and the decline of GPX4 expression suggested that HE might induce ferroptosis as an anti-BLCA process. Shrunk mitochondria and apoptotic bodies were observed in BLCA cells treated with HE, with reduced or absent mitochondrial cristae. We propose for the first time that HE could inhibit the proliferation and migration of BLCA cells and promote apoptosis and ferroptosis. HE may act by targeting proteins such as SRC, PIK3R1 and MAPK1 and the PI3K/AKT pathway.

A candidate prognostic biomarker: TFEB inhibits tumor progression via elevating CDKN1A in bladder cancer.

Bladder cancer(BC) is among the most prevalent malignancies in the world, with 549,393 new cases documented in 2018, and most BC patients have a poor prognosis. Transcription factor EB (TFEB) is considered a crucial controller of lysosomal-associated diseases, but a growing number of research in recent years have reported that TFEB plays other functions in tumors independent of lysosomal autophagy. In this study, we aimed to assess whether TFEB is a biomarker for BC and a molecular target for BC therapy. TFEB was lowly expressed in BC tissues relative to paracancerous tissues, and its elevated expression was strongly associated to a better prognosis for BC patients. TFEB overexpression markedly suppressed cell proliferation, limited cell migration, and accelerated apoptosis. Tumor growth in vivo was also suppressed. Mechanistically, we found that TFEB promoted CDKN1A expression by binding to the upstream progenitor of the CDKN1A promoter, which was also dependent on p53. Finally, Immune cell infiltration in BC tissues, PDL-1 expression, and Single-cell RNA sequencing data revealed immunotherapy may have a positive correlation with TFEB expression. Our study identifies that TFEB regulates CDKN1A in BC and has a positive prognostic value, while its expression is also positively correlated with immune cell infiltration. Therefore, TFEB may represent a recent therapeutic target for BC.

Longitudinal detection of subcategorized CD44v6+ CTCs and circulating tumor endothelial cells (CTECs) enables novel clinical stratification and improves prognostic prediction of small cell lung cancer: A prospective, multi-center study.

Current management of small cell lung cancer (SCLC) remains challenging. Effective biomarkers are needed to subdivide patients presenting distinct treatment response and clinical outcomes. An understanding of heterogeneous phenotypes of aneuploid CD31- circulating tumor cells (CTCs) and CD31+ circulating tumor endothelial cells (CTECs) may provide novel insights in the clinical management of SCLC. In the present translational and prospective study, increased cancer metastasis-related cell proliferation and motility, accompanied with up-regulated mesenchymal marker vimentin but down-regulated epithelial marker E-cadherin, were observed in both lentivirus infected SCLC and NSCLC cells overexpressing the stemness marker CD44v6. Aneuploid CTCs and CTECs expressing CD44v6 were longitudinally detected by SE-iFISH in 120 SCLC patients. Positive detection of baseline CD44v6+ CTCs and CD44v6+ CTECs was significantly associated with enhanced hepatic metastasis. Karyotype analysis revealed that chromosome 8 (Chr8) in CD44v6+ CTCs shifted from trisomy 8 towards multiploidy in post-therapeutic patients compared to pre-treatment subjects. Furthermore, the burden of baseline CD44v6+ CTCs (t0) or amid the therapy (t1-2), the ratio of baseline CD31+ CTEC/CD31- CTC (t0), and CTC-WBC clusters (t0) were correlated with treatment response and distant metastases, particularly brain metastasis, in subjects with limited disease (LD-SCLC) but not in those with extensive disease (ED-SCLC). Multivariate survival analysis validated that longitudinally detected CD44v6+/CD31- CTCs was an independent prognostic factor for inferior survival in SCLC patients. Our study provides evidence for the first time that comprehensive analyses of CTCs, CTECs, and their respective CD44v6+ subtypes enable clinical stratification and improve prognostic prediction of SCLC, particularly for potentially curable LD-SCLC.

Properties of flavonoids in the treatment of bladder cancer (Review).

Given its high recurrence and rapid progress, bladder cancer (BLCA) treatment has become a major problem for clinicians. BLCA is difficult to control even with surgical resection and extensive use of chemotherapeutic drugs. The non-toxicity and ease of accessibility of natural compounds have attracted much attention in recent years. Flavonoids serve an essential role given their antioxidant, antibacterial, anticancer and cardiovascular properties. They are mainly divided into several subclasses; flavones, flavanones, flavonols, flavanols, anthocyanins isoflavones and chalcones. Over the years, the role of flavonoids in BLCA has been extensively studied. The present review provided a comprehensive overview of the classification of flavonoids and substantiate the role of epithelial-mesenchymal transition, cancer stem cells, angiogenesis, epigenetic regulation and programmed cell death in BLCA. The present review emphasized that flavonoids for BLCA treatment are worthy of further study and anti-BLCA drugs have huge prospects for clinical use.

LAMTOR3 is a prognostic biomarker in kidney renal clear cell carcinoma.

OBJECTIVE: The objective of the study was to investigate the expression of LAMTOR3 in kidney renal clear cell carcinoma (KIRC) and its clinical significance. METHODS: The expression of LAMTOR3 in KIRC and its relationship with clinical features were analyzed using the UALCAN online database. The results were verified using KIRC gene chip data and clinical specimens. The prognosis of KIRC patients was analyzed with the GEPIA2 database. GO, KEGG, and GSEA analyses were conducted to analyze the possible molecular mechanism of LAMTOR3 in KIRC. Immunohistochemical (IHC) and hematoxylin and eosin (H&E) staining were used for histopathological detection. RESULTS: UALCAN database analysis showed that LAMTOR3 expression in KIRC was significantly lower than in normal kidney tissues and correlated with the clinical stage, pathological grade, and tumor genotype (p < .05). GSE53757 dataset analysis consistently showed that the expression of LAMTOR3 in KIRC was significantly lower than in normal kidney tissues (p < .01). GEPIA2 database analysis indicated that patients with low LAMTOR3 expression had poor overall and disease-free survival rates. GSEA analysis suggested that LAMTOR3 positively regulated the citrate cycle and drug metabolism cytochrome P450 and negatively regulated folate biosynthesis and olfactory transduction. The expression of LAMTOR3 in KIRC was also significantly correlated with immune cell infiltration. Finally, IHC showed that LAMTOR3 expression in the KIRC tissues was lower than in the adjacent normal tissues. CONCLUSION: LAMTOR3 expression is significantly lower in KIRC. LAMTOR3 may be a potential marker for KIRC diagnosis and therapy.

Application effects of targeted nursing model in patients undergoing thyroid surgery and its influence on patients' negative emotions.

OBJECTIVE: To explore the effectiveness of a targeted nursing model for patients undergoing thyroid surgery, and to analyse the influence of intervention on the negative emotions of patients. METHODS: Eighty patients who received thyroid surgery in our hospital were enrolled and divided into a study group (n=40, given targeted nursing) and a control group (n=40, given routine surgical nursing) according to the difference of intervention measures. The postoperative bed-leaving time, hospitalization time, medical expenses, drainage tube indwelling time and incidence of postoperative adverse reactions were compared between the two groups. The degree of pain, anxiety and depression was compared between the two groups at 1 d, 3 d, 5 d, and 7 d after surgery. The scales of voice handicap index (VHI-10) and standard swallowing assessment (SSA) were used to evaluate voice quality and swallowing function in the two groups. RESULTS: The postoperative bed-leaving time, hospitalization time, medical expenses, drainage tube indwelling time and incidence of postoperative adverse reactions of patients in the study group were lower than those in the control group (P<0.05). The scores of visual analogue scale (VAS), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) in the study group at 3 d, 5 d and 7 d after surgery were lower than those in the control group (P<0.05). The scores of VHI-10 and SSA in the study group were lower than those in the control group at 7 d and 30 d after surgery (P<0.05). CONCLUSION: Targeted nursing for patients undergoing thyroid surgery can help accelerate the improvement of postoperative clinical symptoms, relieve the unhealthy emotions and pain of patients, and help improve their voice quality and swallowing function, which also has a positive effect on reducing postoperative complications. Therefore, it is worthy of clinical popularization and application.

The effect of online training-based continuous nursing care for rectal cancer-patients undergoing permanent colostomy.

OBJECTIVE: The study explored and analyzed the effects of online training based continuous nursing care on the health-related life quality and self-care ability of rectal cancer patients undergoing permanent colostomy. METHODS: A total of 119 patients who were hospitalized and underwent permanent colostomy due to rectal cancer from January 2018 to December 2019 were collected as research subjects and were divided into the control group (n=57) and the observation group (n=62) based on their admission time. The control group received routine nursing, while the observation group was treated with online training based continuous nursing care in addition to routine nursing. Both groups' self-efficacy, self-care ability, quality of life, psychological status and complications within 6 months after discharge were compared. RESULTS: Both groups had increased scores in self-efficacy, and their dimensional scores and total scores of self-care ability after intervention were higher compared with pre-intervention (P<0.05), and the indexes of the observation group after intervention were significantly higher than that of the control group (P<0.05). The two groups had remarkably increased SF-36 scores of each dimension after intervention compared with pre-intervention (P<0.05), and the observation group had apparently higher SF-36 scores than the control group after intervention (P<0.05). The two groups had increased SAS and SDS grades in post-intervention compared with pre-intervention (P<0.05), and the observation group had notably higher SAS and SDS scores than the control group (P<0.05). The complication rate within 6 months after discharge in the observation group was obviously lower than which in the control group (P<0.05). CONCLUSION: An online training based continuous caring model can effectively improve the self-care ability and self-efficacy of rectal cancer patients with permanent enterostomy, thus promoting better life quality and psychological states, and effectively reducing the incidence of complications after discharge.

The effect of evidence-based nursing program of progressive functional exercise of affected limbs on patients with breast cancer-related lymphoedema.

OBJECTIVE: This study explored and analyzed the effect of evidence-based nursing program of progressive exercise on patients with breast cancer-related lymphoedema. METHODS: 78 breast cancer patients who underwent breast cancer surgery in our hospital from January to December 2018 were chosen as the control group, and 83 patients enrolled from January to December 2019 with the same condition were selected as the observation group. The control group was given routine nursing measures after surgery, while the observation group was given the evidence-based nursing (EBN) program of progressive functional exercise on affected limbs after breast cancer surgery. The postoperative lymphedema, function recovery of upper limb, score of quality life and the satisfaction of patients to nursing were compared between the two groups. RESULTS: The degree of lymphedema in the observation group was significantly lower than that in the control group 4 weeks after surgery (P<0.05). The limb lifting function, abduction function and rotatory function of the observation group were significantly superior to those of the control group (P<0.05). The scores of physiological status, emotional status, functional status and additional concerns in the observation group were significantly higher than those in the control group 4 weeks after operation (25.46±3.97 vs. 16.95±4.17; 24.74±3.11 vs. 17.42±2.86; 25.48±1.69 vs. 25.48±1.69; 24.51±4.12 vs. 18.32±2.56) (P<0.05). There was no significant difference in social/family status scores between the two groups (P>0.05). Additionally, the satisfaction of patients in the observation group to nursing care was also significantly higher than that in control group (P<0.05). CONCLUSION: The evidence-based nursing program of progressive exercise can effectively reduce the lymphedema of patients after breast cancer surgery, improve their postoperative upper limbs function, and effectively promote the quality of life and nursing satisfaction, which is worthy of clinical promotion.

Association Between Arg72Pro Polymorphism in TP53 and Malignant Abdominal Solid Tumor Risk in Hunan Children.

Pediatric solid tumors are heterogeneous and comprise various histological subtypes. TP53, a tumor suppressor, orchestrates the transcriptional activation of anti-cancer genes. The gene coding for this protein is highly polymorphic, and its mutations are associated with cancer development. The Arg72Pro polymorphism in TP53 has been associated with susceptibility to various types of cancer. Here, in this hospital-based study, we evaluated the association of this polymorphism with susceptibility toward malignant abdominal solid tumors in children in the Hunan province of China. We enrolled 162 patients with neuroblastoma, 60 patients with Wilms' tumor, and 28 patients with hepatoblastoma as well as 270 controls. Genotypes were determined using a TaqMan assay, and the strength of the association was assessed using an odds ratio, within a 95% confidence interval identified using logistic regression models. Our results showed that the Arg72Pro polymorphism did not exhibit significant association with susceptibility toward pediatric malignant abdominal solid tumors. Stratification analysis revealed that this polymorphism exerts weak sex- and age-specific effects on Wilms' tumor and hepatoblastoma susceptibility, respectively. Overall, our results indicate that the Arg72Pro polymorphism may have a marginal effect on susceptibility toward pediatric malignant abdominal solid tumors in Hunan, and this finding warrants further confirmation.

Feedback activation of GATA1/miR-885-5p/PLIN3 pathway decreases sunitinib sensitivity in clear cell renal cell carcinoma.

Sunitinib is the most commonly used first-line therapy for the treatment of advanced renal cell carcinoma (RCC), but intrinsic and extrinsic resistance to targeted therapies dramatically compromise the benefit of clinical outcome. Dissecting the underlying mechanisms and discovering reliable predictive biomarkers are urgently needed in clinic. Here, we discovered miR-885-5p was notably decreased after sunitinib treatment and associated with poor disease progression in clear cell renal cell carcinoma (ccRCC). In vitro and in vivo studies identified miR-885-5p inhibition contributed to sunitinib resistance. Mechanistically, sunitinib treatment reduced GATA1 expression, which in turn reduced its binding to MIR885 promoter and resulted in miR-885-5p downregulation in transcriptional level. In addition, PLIN3 was confirmed to be directly targeted by miR-885-5p and its upregulation significantly increased lipid droplets formation to decrease sunitinib sensitivity. Therefore, GATA1/miR-885-5p/ PLIN3 pathway may serve as a potential therapeutic strategy and a biomarker for sunitinib treatment in ccRCC.

Novel circRNA_0071196/miRNA­19b­3p/CIT axis is associated with proliferation and migration of bladder cancer.

Circular RNAs (circRNAs) are non­coding RNAs that are connected at the 3' and 5' ends by an exon or intron. Studies increasingly show that circRNAs play an important role in tumorigenesis by acting as a 'sponge' for microRNAs (miRNAs), which abrogates the latter's effect on their target mRNAs. To identify a possible circRNA/miRNA/mRNA network in bladder cancer (BCa), we analyzed the circRNA and mRNA expression profiles of BCa and adjacent normal bladder tissues. A total of 127 circRNAs and 1,612 mRNAs were differentially expressed in the tumor tissues, and were primarily associated with cancer­related pathways. A competing endogenous RNAs (ceRNA) network was then constructed which predicted a regulatory axis of circRNA_0071196, miRNA­19b­3p and its target gene citron Rho­interacting serine/threonine kinase (CIT). Luciferase reporter assay validated the relationship between circRNA_0071196 and miRNA­19b­3p and of the latter with CIT. Furthermore, CIT was overexpressed in the BCa tissues, and was found to be correlated with metastasis and tumor histological grade. Knockdown of CIT in the human bladder cancer cell line 5367 significantly inhibited the proliferation, migration and colony formation capacity of the cells, and also upregulated the mediators of the p53 and RhoA­ROCK signaling cascades that regulate cell cycle and migration. Taken together, our findings indicate that circRNA­0071196 upregulates CIT levels in BCa by sponging off miRNA­19b­3p, and the circRNA_0071196/miRNA­19b­3p/CIT axis is a potential therapeutic target in BCa.

Down-regulation of CIT can inhibit the growth of human bladder cancer cells.

OBJECTIVE: Our study is to examine the citron rho-interacting, serine/threonine kinase 21 (CIT) in bladder cancer. METHODS: We examined CIT level in human bladder cancer tissues by immunohistochemical staining. To explore the impact of CIT on cell proliferation and apoptosis, we down-regulated its expression in two human bladder cancer cell lines, 5367 and T24. We examined cell growth in 5367 and T24. We also performed in vivo analysis using T24 cells. We further used microarray expression profiling to investigate genes differentially expressed in T24 cells with CIT down-regulated. RESULTS: In 100 human samples, CIT was expressed by only 2 of 30 (6.7 %) controls in bladder tissues, whereas by 64 of 70 (91.4 %) cancer patients in tumor tissues (p < 0.001). in vitro analysis demonstrated that CIT knockdown represses cell proliferation by 50 % in both cells and colony formation (77 ± 5 vs. 13 ± 2, p = 0.001 for T24, 58 ± 3 vs. 1 ± 1, p < 0.001 for 5637). We also found CIT knockdown could induce cell cycle arrest, and promote apoptosis in both cells. Tumor-volume monitoring and live in vivo bladder cancer imaging in human xenograft model confirmed that CIT knockdown reduces tumor volume (668.4 ± 333.0 vs. 305.7 ± 170.4 mm3, p = 0.02) and weight (0.27 ± 0.15 vs. 0.57 ± 0.32 g, p = 0.02). Microarray analysis revealed that CIT may regulate cell cycle signalling pathway through various cell cycle regulators. CONCLUSIONS: In summary, we provided clinical and experimental evidence that CIT may promote bladder cancer through regulation of cell cycle pathway.

Melanotic neuroectodermal tumor of infancy in ovary: A rare case report.

RATIONALE: Melanotic neuroectodermal tumor of infancy (MNTI) is an extremely rare benign pigmented neoplasm of neural crest origin with rapid expansile growth and a high recurrence rate. It is predominantly found in infants of <1 year of age, involvement of the head-and-neck region is the most common presentation though it is reported at other sites including mediastinum, shoulder, thigh, foot, epididymis, uterus and ovary. The patient reported here is the third case of MNTI presenting in an ovary, and the first reported in the infant ovary. PATIENT CONCERNS: A 33-month-old girl was presented to our unit for a huge abdominal mass. DIAGNOSIS: MNTI was eventually diagnosed by histological manifestations supplemented with immunohistochemical findings. INTERVENTIONS: Exploratory laparotomy and complete resection were conducted successfully. OUTCOMES: Postoperative course was uneventful and no recurrence was displayed in the 6-month follow-up. LESSONS: This case emphasizes that pediatric surgeons and pathologists must always consider the possibility of MNTI while dealing with ovarian neoplasms in infants. Although considered to be a benign tumor, proper treatment and close clinicoradiological follow-up of this tumor are of great importance.

miR-34b/c rs4938723 T>C Decreases Neuroblastoma Risk: A Replication Study in the Hunan Children.

Neuroblastoma is the most common seen solid neural tumor in children less than age one. As mutation in the miR-34b/c gene is observed in several types of human malignancies, there likely to be similar events that contribute to the pathogenesis of neuroblastoma. We hypothesize that polymorphism in the miR-34b/c gene might predispose to neuroblastoma. Here, we conducted this replication study by genotyping rs4938723 T>C from miR-34b/c in Hunan children (162 subjects with neuroblastoma and 270 control subjects) and examined its effect on the risk of neuroblastoma. We determined such association using logistic regression, adjusted for age and gender. Relative to those with TT genotype, subjects with C allele had reduced neuroblastoma risk (TC vs. TT: adjusted OR = 0.46, 95%CI = 0.30-0.71; additive model: adjusted OR = 0.64, 95%CI = 0.47-0.88; TC/CC vs. TT: adjusted OR = 0.49, 95%CI = 0.33-0.73). Stratified analysis revealed that rs4938723 TC/CC carriers were less likely to develop neuroblastoma for patients in the subgroups of age ≤ 18 months, age > 18 months, females, males, tumors in retroperitoneal, tumors in other sites, and clinical stages II, III, IV, and III+IV. Our findings verified miR-34b/c rs4938723 C variant allele as a protective factor for the risk of neuroblastoma. Further investigation of how miR-34b/c rs4938723 T>C might modify neuroblastoma risk is warranted.

GPER stabilizes F-actin cytoskeleton and activates TAZ via PLCß-PKC and Rho/ROCK-LIMK-Cofilin pathway.

Actin is a highly abundant cytoskeletal protein that is essential for all eukaryotic cells and participates in many structural and functional roles. It has long been noted that estrogen affects cellular morphology. However, recent studies observed that both estrogen and tamoxifen induce a remarkable cytoskeletal remodeling independent of ER. In addition to ER, G protein-coupled estrogen receptor 1 (GPER, also known as GPR30) also binds to estrogen with high affinity and mediates intracellular estrogenic signaling. Here, we show that activation of GPER by its specific agonist G-1 induces re-organization of F-actin cytoskeleton. We further demonstrate that GPER acts through PLCß-PKC and Rho/ROCK-LIMK-Cofilin pathway, which are upstream regulators of F-actin cytoskeleton assembly, thereby enhancing TAZ nuclear localization and activation. Furthermore, we find that LIMK1/2 is critical for GPER activation-induced breast cancer cell migration. Together, our results suggest that GPER mediates G-1-induced cytoskeleton assembly and GPER promotes breast cancer cell migration via PLCß-PKC and Rho/ROCK-LIMK-Cofilin pathway.

Additional data support the role of LINC00673 rs11655237 C>T in the development of neuroblastoma.

Neuroblastoma is the most frequently diagnosed neural tumor of childhood. Abnormal function of the long intergenic non-coding RNA (lincRNA) LINC00673 has been implicated in various human malignancies. Genome-wide association studies revealed the LINC00673 rs11655237 C>T polymorphism to be associated with the risk of neuroblastoma, though the effect was not well defined, in part due to the small sample size in our earlier study. Herein, we verified the impact of LINC00673 rs11655237 C>T on the risk of neuroblastoma in 700 cases and 1516 controls from six centers in China. After pooling all enrolled patients, we observed a significant association between LINC00673 rs11655237 C>T and risk of neuroblastoma (TT vs. CC: adjusted odds ratio [OR]=1.58, 95% confidence interval [CI]=1.06-2.35, P=0.024; additive model: adjusted OR=1.20, 95% CI=1.03-1.39, P=0.020; recessive model: adjusted OR=1.50, 95% CI=1.02-2.22, P=0.040). Stratification analysis revealed a significant relationship between rs11655237 CT/TT and neuroblastoma risk in subgroups of males, patients whose tumor originated in the adrenal gland, and patients with clinical stage IV disease. These findings add new evidence of the importance of LINC00673 rs11655237 C>T to the risk of developing neuroblastoma.

[Experience of diagnosis and treatment for 89 patients with Marjolin's ulcers in lower limbs].

OBJECTIVE: To summarize the clinical features of Marjolin's ulcers in lower limbs and the diagnosis and treatment methods for it.
 Methods: The clinical data of 89 patients with lower limbs Marjolin's ulcers, who were treated in Xiangya Hospital, Central South University from Jan 1998 to Dec 2017, were retrospectively analyzed, including demographics, injury factors, length of cancer incubation period, lesion location, ulcer area, pathological type, bone invasion, lymph node metastasis, surgical methods, repair methods and prognosis.
 Results: There were 70 males and 19 females among 89 patients with lower limbs Marjolin's ulcers. The most common injuries were flame burn (42 cases), trauma (19 cases), and burns (12 cases). The lesions were most common in the lower leg (31 cases), followed by the thigh (11 cases) and the heel (11 cases). The ulcer area was 1.5-600.0 cm2. There were 80 cases of squamous cell carcinoma, 8 cases of verrucous carcinoma, and 1 case of sarcoma. Before operation, 78 cases of inguinal lymphadenectasis were found, 49 cases of inguinal lymph node dissection, 29 cases of simple lymph node biopsy and resection, and 9 cases of lymph node metastasis and 8 cases of bone invasion were observed; 24 cases of amputation, 53 cases of extended resection and skin grafts, and 12 patients of extensive resection and flap transplantation were performed. Sixty-five cases were followed up, and 8 cases recurred, including 2 cases of amputation patients and 6 cases of extended resection patients. There was no relationship between recurrence of tumors and surgical methods (P>0.05).
 Conclusion: The recurrence and metastasis rate of Marjolin's ulcers in lower limbs is high, requiring early detection, early diagnosis, early surgical treatment and regular follow-up. Lnguinal lymphadenectasis is more common and requires lymph node biopsy and lymphadenectomy, or lymph node dissection. Extended local resection, skin graft or flap repair is the main treatment methods. However, amputation can be considered if the cancer is big, the invasion is deep, and the lower extremity scar is extensive and combined with severe deformity.

Investigating the mechanism by which SMAD3 induces PAX6 transcription to promote the development of non-small cell lung cancer.

BACKGROUND: This study investigated the function of SMAD3 (SMAD family member 3) in regulating PAX6 (paired box 6) in non-small cell lung cancer. METHODS: First, qRT-PCR was employed to detect SMAD3 expression in cancer tissues along with normal tissues and four cell lines, including BEAS-2B, H125, HCC827 and A549 cells. SMAD3 was knocked down by small interference RNA (siRNA), and then its expression was determined via qRT-PCR and Western blot analysis. The correlation between SMAD3 and PAX6 was determined by double luciferase reporter experiments and chromatin immunoprecipitation (ChIP) assay. Cell viability was evaluated by CCK-8 and colony forming assays, while cell migration and invasion were detected by Transwell analysis. RESULTS: SMAD3 and PAX6 were upregulated in lung cancer tissues and cancer cells. Knocking down SMAD3 and PAX6 by transfection with siRNAs specifically suppressed the expression of SMAD3 and PAX6 mRNA and protein levels. SMAD3 could promote PAX6 transcriptional activity by binding to its promoter. Reduced expression of SMAD3 led to the downregulation of PAX6 mRNA and protein levels along with decreased cell migration, invasion, proliferation and viability in A549 and HCC827 cells. PAX6 overexpression altered the si-SMAD3-induced inhibition of cell migration, invasion, proliferation and viability in A549 and HCC827 cells. Additionally, PAX6 knockdown alone also repressed the cell migration, invasion, proliferation and viability of the cell lines. CONCLUSIONS: SMAD3 promotes the progression of non-small cell lung cancer by upregulating PAX6 expression.