Knockdown of CXCL5 inhibits the invasion, metastasis and stemness of bladder cancer lung metastatic cells by downregulating CD44.

In our previous studies, we found that T24 lung metastatic cancer cells showed high invasion and metastasis abilities and cancer stem cell characteristics compared with T24 primary cancer cells. By screening for the expression of CXC chemokines in both cell lines, we found that CXCL5 is highly expressed in T24-L cells. The aim of this study is to shed light on the relationship of CXCL5 with epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). RNAi technology was used to decrease CXCL5 expression in the T24-L cell line, and the EMT and CSCs of the shCXCL5 group and the control group were compared. The CXCR2 inhibitor SB225002 was used to inhibit the receptor of CXCL5 to determine the effect of the CXCL5/CXCR2 axis. The knockdown of CXCL5 expression in T24-L cells reduced their EMT and CSC characteristics. RT-PCR and Western blot analyses revealed the downregulation of N-cadherin, Vimentin and CD44. In addition, when CD44 expression was knocked down, the EMT ability of the cells was also inhibited. This phenomenon was most pronounced when both CXCL5 and CD44 were knocked down. CXCL5 and CD44 can affect the EMT and stem cell capacity of T24-L cells through some interaction.

Positive feedback in Cav-1-ROS signalling in PSCs mediates metabolic coupling between PSCs and tumour cells.

Caveolin-1 (Cav-1) is the principal structural component of caveolae, and its dysregulation occurs in cancer. However, the role of Cav-1 in pancreatic cancer (PDAC) tumorigenesis and metabolism is largely unknown. In this study, we aimed to investigate the effect of pancreatic stellate cell (PSC) Cav-1 on PDAC metabolism and aggression. We found that Cav-1 is expressed at low levels in PDAC stroma and that the loss of stromal Cav-1 is associated with poor survival. In PSCs, knockdown of Cav-1 promoted the production of reactive oxygen species (ROS), while ROS production further reduced the expression of Cav-1. Positive feedback occurs in Cav-1-ROS signalling in PSCs, which promotes PDAC growth and induces stroma-tumour metabolic coupling in PDAC. In PSCs, positive feedback in Cav-1-ROS signalling induced a shift in energy metabolism to glycolysis, with up-regulated expression of glycolytic enzymes (hexokinase 2 (HK-2), 6-phosphofructokinase (PFKP) and pyruvate kinase isozyme type M2 (PKM2)) and transporter (Glut1) expression and down-regulated expression of oxidative phosphorylation (OXPHOS) enzymes (translocase of outer mitochondrial membrane 20 (TOMM20) and NAD(P)H dehydrogenase [quinone] 1 (NQO1)). These events resulted in high levels of glycolysis products such as lactate, which was secreted by up-regulated monocarboxylate transporter 4 (MCT4) in PSCs. Simultaneously, PDAC cells took up these glycolysis products (lactate) through up-regulated MCT1 to undergo OXPHOS, with down-regulated expression of glycolytic enzymes (HK-2, PFKP and PKM2) and up-regulated expression of OXPHOS enzymes (TOMM20 and NQO1). Interrupting the metabolic coupling between the stroma and tumour cells may be an effective method for tumour therapy.

Survival benefit of vaginectomy compared to local tumor excision in women with FIGO stage I and II primary vaginal carcinoma: a SEER study.

PURPOSE: The effectiveness of vaginectomy compared to that of local tumor excision (LTE) for the International Federation of Gynecology and Obstetrics (FIGO) stage I and II vaginal carcinoma is unclear. We aimed to clarify if the effectiveness of vaginectomy is comparable to that of LTE in the real world. METHODS: We retrospectively evaluated data of patients with primary vaginal carcinoma registered in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2016. The multivariate Cox proportional hazards models and Fine-Gray competing risk models were used to estimate the overall survival (OS) and disease-specific survival (DSS) after propensity score matching. RESULTS: Of the 533 patients with FIGO stage I and II primary vaginal carcinoma, 243 and 290 patients were treated with vaginectomy and LTE, respectively. Vaginectomy was significantly associated with improved OS [unadjusted hazard ratio (HR) = 0.70, 95% confidence interval (CI) 0.53-0.95, P = 0.020; adjusted HR = 0.63, 95% CI 0.46-0.87, P = 0.005] and DSS [unadjusted subdistribution HR (sHR) = 0.75, 95% CI 0.52-1.07, P = 0.115; adjusted sHR = 0.65, 95% CI 0.44-0.97, P = 0.036]. Age, marital status, histology type, FIGO stage, chemotherapy, and lymph node metastases were significant prognostic factors of survival. Moreover, radiotherapy did not influence the effectiveness of vaginectomy. Subgroup and sensitivity analysis confirmed the consistent beneficial effectiveness of vaginectomy. CONCLUSION: Compared with LTE, vaginectomy results in significantly prolonged survival in patients with FIGO stage I and II primary vaginal carcinoma. Thus, it can be the preferred treatment for FIGO I and II vaginal cancer regardless of radiotherapy status.

Theoretical study on the Cerenkov-type second-harmonic generation in optical superlattices without paraxial approximation.

In this paper, the Cerenkov-type second-harmonic generation in bulk optical superlattices has been studied theoretically with the non-paraxial wave equations, where the paraxial approximation is avoided. The corresponding phase-matching condition is determined strictly by solving the non-paraxial wave equations under proper boundary conditions, and the result coincides well with the traditional Cerenkov phase-matching condition. In addition, a backward Cerenkov phase-matching condition is deduced from the wave equations as well, and the physical requirement of this condition is clarified.

2D wave-front shaping in optical superlattices using nonlinear volume holography.

Nonlinear volume holography is employed to realize arbitrary wave-front shaping during nonlinear processes with properly designed 2D optical superlattices. The concept of a nonlinear polarization wave in nonlinear volume holography is investigated. The holographic imaging of irregular patterns was performed using 2D LiTaO3 crystals with fundamental wave propagating along the spontaneous polarization direction, and the results agree well with the theoretical predictions. This Letter not only extends the application area of optical superlattices, but also offers an efficient method for wave-front shaping technology.

Nonlinear optical Fourier transform in an optical superlattice with "x+2" structure.

We proposed a simple method to realize optical Fourier transform during the nonlinear wave shaping processes. In this method, an integrated optical superlattice is designed to realize multiple optical functions, which plays important roles in both the nonlinear harmonic generation process and the optical Fourier Transform process. We demonstrated our method by the nonlinear generation of Airy beams as an example. It is a universal method for beam shaping and is of practical importance for designing compact nonlinear optical devices.

Au-allenylidene promoted decarboxylative annulation to access unsaturated γ-lactams/lactones.

A novel Au-allenylidene promoted decarboxylative annulation by intramolecular α-nucleophilic addition has been disclosed. The unsaturated cyclic ethynylethylene carbamates/carbonates can be converted to unique nucleophiles attached with alkylidene ketenes by sequential decarboxylation and oxidation processes. Such alkylidene ketenes can be rapidly trapped by intramolecular α-attacking annulation to generate potential biological active unsaturated γ-lactams/lactones with broad scope, facile post-modification, high regioselectivity and efficiency.

Synthesis of thioesters using an electrochemical three-component reaction involving elemental sulfur.

An electrochemical three-component reaction involving elemental sulfur is disclosed for achieving a metal-free, oxidant-free synthesis of thioesters in a high atom-economical, step-economical and chemoselective manner. A mechanistic investigation indicates that the use of elemental sulfur to trap acyl radical derived from radical umpolung of α-keto acid with an electrochemical design can efficiently generate a carbonyl thiyl radical, which can further be captured by diazoalkane to afford various thioesters.

NEIL3 promotes cell proliferation of ccRCC via the cyclin D1-Rb-E2F1 feedback loop regulation.

Nei endonuclease VIII-like 3 (NEIL3), a novel tumor-related gene, is differentially expressed and involved in pathophysiological processes in multiple tumors. However, the potential biological functions and molecular mechanisms of NEIL3 in human clear cell renal cell carcinoma (ccRCC) have not been identified. In this research, we demonstrated that NEIL3, transcriptionally activated by E2F1, served as an oncogene to facilitate cell proliferation and cell cycle progression and contribute to tumorigenesis via the cyclin D1-Rb-E2F1 feedback loop in ccRCC. First, we found that NEIL3 expression was upregulated in ccRCC tissues and cell lines compared with matched adjacent nontumor tissues and renal tubular epithelial cells and was also positively correlated with adverse clinicopathological characteristics, such as advanced cancer stages and higher tumor grades, and acted as an independent prognostic marker in ccRCC. Mechanistically, we demonstrated that NEIL3 promoted cell proliferation, DNA replication and cell cycle progression in vitro and tumor growth in vivo. Furthermore, we found that NEIL3 overexpression activated the cyclin D1-Rb-E2F1 pathway, and the E2F1 upregulation transcriptionally activated NEIL3 expression, thus forming a feedback loop. In addition, there was a positive correlation between NEIL3 and E2F1 expression in clinical specimens of ccRCC. Taken together, our results suggest that NEIL3 serves as a proto-oncogene in ccRCC and presents as a novel candidate for ccRCC diagnosis and treatment.

Abundance and diversity of ammonia-oxidizing archaea in response to various habitats in Pearl River Delta of China, a subtropical maritime zone.

Ammonia-oxidizing archaea (AOA) are widely considered key to ammonia oxidation in various environments. However, little work has been conducted to simultaneously investigate the abundance and diversity of AOA as well as correlations between archaeal amoA genotypes and environmental parameters of different ecosystems at one district. To understand the abundance, diversity, and distribution of AOA in Pearl River Delta of China in response to various habitats, the archaeal amoA genes in soil, marine, river, lake, hot spring and wastewater treatment plant (WWTP) samples were investigated using real-time fluorescent quantitative PCR and clone libraries. Our analyses indicated that the diversity of AOA in various habitats was different and could be clustered into five major clades, i.e., estuary sediment, marine water/sediment, soil, hot spring and Cluster 1. Phylogenetic analyses revealed that the structure of AOA communities in similar ecological habitats exhibited strong relation. The canonical correspondence method indicated that the AOA community structure was strongly correlated to temperature, pH, total organic carbon, total nitrogen and dissolved oxygen variables. Assessing AOA amoA gene copy numbers, ranging from 6.84 x 10(6) to 9.45 x 10(7) copies/g in dry soil/sediment, and 6.06 x 10(6) to 2.41 x 10(7) copies/L in water samples, were higher than ammonia-oxidizing bacteria (AOB) by 1-2 orders of magnitude. However, AOA amoA copy numbers were much lower than AOB in WWTP activated sludge samples. Overall, these studies suggested that AOA may be a major contributor to ammonia oxidation in natural habitats but play a minor role in highly aerated activated sludge. The result also showed the ratio of AOA to AOB amoA gene abundance was positively correlated with temperature and less correlated with other environmental parameters. New data from our study provide increasing evidence for the relative abundance and diversity of ammonia-oxidizing archaea in the global nitrogen cycle.

[One-step methylation variable position analysis technology in single-tube].

OBJECTIVE: To develop the single-tube one-step methylation variable position (MVP) analysis technology-single-tube post-digestion PCR-melting curve analysis (PDP-MCA). METHODS: Based on differentially methylated region (DMR) reported previously as the model, a set of primers with different melting temperatures of products in the two sides of MVP were designed. By using the FastDigest methylation-sensitive restriction enzyme (MSRE), DNA digestion, multiplex amplification, MCA detection and MCA profiles were performed in a single reaction tube. Same samples (peripheral venous blood, semen, and vaginal fluid, 5 samples each type) were tested by single-tube one step MVP and traditional MSRE-PCR MCA technology. To verify the feasibility of this method, the results were compared with that of the traditional technology. The MCA/HRM profiles of different samples were analyzed and compared. RESULTS: When the melting temperature of the fragments had a differential of 2 degrees C, the MCA melting peaks separated well, and MCA detection after multiplex amplification was successful. The single-tube PDP-MCA assay was developed, which integrated multiple reactions (digestion, amplification and detection) into one tube. By this method, the sample-specific profiles and data were analyzed in 2 h, which is similar to that of the traditional method. The rapid classifications of the samples were also realized. CONCLUSION: Multiplex MVPs can be analyzed in a single closed-tube. The single-tube PDP-MCA technology is a simple, fast, and automatable method. It can be used for detection of DNA methylation variations.

PAQR5 inhibits the growth and metastasis of clear cell renal cell carcinoma by suppressing the JAK/STAT3 signaling pathway.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) has a high degree of malignancy and poor overall prognosis in advanced and metastatic patients. Therefore, it is of great significance to find new prognostic biomarkers and therapeutic targets for ccRCC. The expression of progestin and adipoQ receptor family member 5 (PAQR5) is significantly downregulated in ccRCC compared with normal tissues, but its specific mechanism and potential biological function in ccRCC remain unclear. METHODS: The expression pattern of PAQR5 and the correlation between the PAQR5 expression and clinicopathological parameters and various survival periods in ccRCC patients were analyzed by using multiple public databases and ccRCC tissues chip. Its prognostic value was analyzed by univariate/multivariate Cox regression. In addition, MTT assay, EdU staining assay, flow cytometry, wound healing assay, transwell migration and invasion assay, colony formation assay, immunofluorescence assay, and a xenograft tumor model were conducted to assess the biological function of PAQR5 in ccRCC in vitro and in vivo. RESULTS: Our results indicated that the downregulation of PAQR5 was demonstrated in ccRCC tumor tissues and associated with poorer OS, DSS, and PFI. Meanwhile, the univariate/multivariate Cox regression analysis confirmed that PAQR5 might serve as an independent prognostic factor for ccRCC, and its low expression was tightly correlated with tumor progression and distant metastasis. Mechanistically, a series of gain- and loss-of-function assay revealed that PAQR5 could suppress the ccRCC proliferation, invasion, metastasis, and tumorigenicity in vitro and in vivo by inhibiting the JAK/STAT3 signaling pathway. CONCLUSION: Our study revealed the tumor suppressor role of PAQR5 in ccRCC. PAQR5 is a valuable prognostic biomarker for ccRCC and may provide new strategies for clinical targeted therapy.

Trends in the Incidence of Vulvar and Vaginal Cancers With Different Histology by Race, Age, and Region in the United States (2001-2018).

Objectives: The race, age, and region-stratified incidence of vulvar (VUC) and vaginal (VAC) cancers with different histology were unclear. Methods: Data was retrieved from the United States Cancer Statistics database. Average annual percent change (AAPC) and incidence rate ratio (IRR) were calculated. Results: Overall, VUC incidence increased from 18.3 (per 1,000,000 woman-years) to 19.6, but VAC incidence decreased from 5.6 to 4.4. VUC squamous cell carcinoma (SCC) incidence increased (AAPC, 0.96; 95% CI, 0.66-1.25), VUC adenocarcinoma (ADE) incidence stabilized (AAPC, -0.24; 95% CI, -1.44 to 0.98), and VUC other malignancies (OM) incidence decreased (AAPC, -1.31; 95% CI, -2.58 to -0.02). While VAC incidence decreased for any histology (AAPC, -0.63; 95% CI, -1.03 to -0.22; AAPC, -1.60; 95% CI, -2.80 to -0.39; and AAPC, -1.57; 95% CI, -2.24 to -0.89 for SCC, ADE, and OM). Similar trends were observed in most of the stratifications. Conclusion: VUC and VAC incidences varied by histology overall and within stratifications by race, age, and region. The incidence decreased for VUC and VAC with all histologies, except for the increasing VUC SCC incidence.

Development and validation of models for predicting the overall survival and cancer-specific survival of patients with primary vaginal cancer: A population-based retrospective cohort study.

Background: No models have been developed to predict the survival probability for women with primary vaginal cancer (VC) due to VC's extreme rareness. We aimed to develop and validate models to predict the overall survival (OS) and cancer-specific survival (CSS) of VC patients. Methods: A population-based multicenter retrospective cohort study was carried out using the 2004-2018 Surveillance, Epidemiology, and End Results Program database in the United States. The final multivariate Cox model was identified using the Brier score and Harrell's C concordance statistic (C-statistic). The decision curve, calibration plot, and area under the time-dependent receiver operating characteristic curve (AUC) were used to evaluate model prediction performance. Multiple imputation followed by bootstrap was performed. Bootstrap validation covered the entire statistic procedure from model selection to baseline survival and coefficient calculation. Nomograms predicting OS and CSS were generated. Results: Of the 2,417 eligible patients, 1,692 and 725 were randomly allocated to the training and validation cohorts. The median age (Interquartile range) was 66 (56-78) and 65 (55-76) for the two cohorts, respectively. Our models had larger net benefits in predicting the survival of VC patients than the American Joint Committee on Cancer stage, presenting great discrimination ability and excellent agreement between the expected and observed events. The performance metrics of our models were calculated in three cohorts: the training cohort, complete cases of the validation cohort, and the imputed validation cohort. For the OS model in the three cohorts, the C-statistics were 0.761, 0.752, and 0.743. The slopes of the calibration plots were 1.017, 1.005, and 0.959. The 3- and 5-year AUCs were 0.795 and 0.810, 0.768 and 0.771, and 0.770 and 0.767, respectively. For the CSS model in the three cohorts, the C-statistics were 0.775, 0.758, and 0.755. The slopes were 1.021, 0.939, and 0.977. And the 3- and 5-year AUCs were 0.797 and 0.793, 0.786 and 0.788, and 0.757 and 0.757, respectively. Conclusion: We were the first to develop and validate exemplary survival prediction models for VC patients and generate corresponding nomograms that allow for individualized survival prediction and could assist clinicians in performing risk-adapted follow-up and treatment.

Piezo1 act as a potential oncogene in pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related death. A growing number of studies believe that matrix stiffness plays an important role in the development of pancreatic disease. As one of the famous mechanically activated cation channels, Piezo1 has received more attention recently. Here we tried to describe the role of Piezo1 on PDAC progression. It seemed that Piezo1 was a potential tumor-promoting marker of pancreatic cancer. By using Yoda1, we measured the intracellular calcium flux mediated by Piezo1 which confirmed it did act as an intrinsic cation channel in pancreatic cancer cells. Additionally, we also found the inhibition of Piezo1 could inhibit cancer progression in vitro; however, Piezo1 activation (induced by Yoda1) had an oppositive effect. Moreover, Piezo1 activation may also accelerate pancreatic cancer tumor growth/formation via modulating pancreatic cancer cell-tumor microenvironment interactions in vivo. We concluded that Piezo1 acted as an oncogenic gene in pancreatic cancer progression. It might be one of promising targets for pancreatic cancer therapy.

Mechanically activated ion channel Piezo1 contributes to melanoma malignant progression through AKT/mTOR signaling.

Melanoma is a highly aggressive cancer that can metastasize at early stage. The aim of this study is to clarify the role of Piezo1 and its potential mechanism in regulating the malignant phenotypes of melanoma. In the present study, we first showed that Piezo1 was abnormally expressed in melanoma, which accelerated the malignant progression by activating AKT/mTOR signaling. Firstly, we found that Piezo1 was upregulated in melanoma and associated with poor survival. Additionally, Piezo1 knockdown significantly weakened intracellular calcium signal and viability of melanoma cells. Furthermore, Piezo1 knockdown inhibited the transendothelial migration and invasion in vitro, as well as metastasis in vivo. Mechanistically, we found that Piezo1 activated AKT/mTOR signaling to maintain malignant phenotypes of melanoma. Therefore, Piezo1 acts as an oncogene in melanoma cells and provides a novel candidate for melanoma diagnosis and treatment.

RASAL2 mediated the enhancement of YAP1/TIAM1 signaling promotes malignant phenotypes of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high incidence of metastasis and dismal prognosis. As a member of Gas-Gap gene, RASAL2 is involved in the hydrolysis of RAS-GTP to RAS-GDP and abnormal expression in human cancers. Here we firstly described the function of RASAL2 on PDAC to enrich the knowledge of RAS family.We interestingly observed that RASAL2 expression was upregulated in PDAC at both mRNA and protein levels, and high expression of RASAL2 predicted a poor prognosis in PDAC patients. Additionally, RASAL2 promoted malignant behaviors of PDAC in vitro and in vivo. To determine the mechanistic roles of RASAL2 signaling and its potential as a therapeutic target in PDAC, we clarified that RASAL2 could accumulate the TIAM1 expression in different level through inhibiting YAP1 phosphorylation, increased TIAM1 mRNA expression and suppressed ubiquitination of TIAM1 protein. In conclusion, RASAL2 enhances YAP1/TIAM1 signaling and promotes PDAC development and progression.

Developing and Validating Novel Nomograms for Predicting the Overall Survival and Cancer-Specific Survival of Patients With Primary Vulvar Squamous Cell Cancer.

Background: To develop and validate novel nomograms for better predicting the overall survival (OS) and cancer-specific survival (CSS) of patients with vulvar squamous cell cancer (VSCC). Methods: A retrospective analysis using a population-based database between 2004 and 2016 was carried. A 10-fold cross-validation with 200 repetitions was used to choose the best fit multivariate Cox model based on the net-benefit of decision curve analysis. Net-benefit, Harrell's C concordance statistic (C-statistic) of calibration plot, and area under the receiver operating characteristic curve (AUC) were used to evaluate the model prediction accuracy. Nomograms of the OS and CSS were generated based on the best fit model. Results: Of the 6,792 patients with VSCC, 5,094 (75%) and 1,698 (25%) were allocated to the training and validation cohort, respectively. All the variables were balanced between the training and validation cohorts. Age, insurance, tumor size, pathological grade, radiotherapy, chemotherapy, invasion depth, lymphadenectomy, sentinel lymph nodes biopsy, surgery, N stage, and M stage were in the best fit model for generating nomograms. The decision curve analysis, calibration plot, and receiver operating characteristic (ROC) curve show the better prediction performance of the model compared to previous studies. The C-statistics of our model for OS prediction are 0.80, 0.83, and 0.81 in the training, validation, and overall cohorts, respectively, while for CSS prediction are 0.83, 0.85, and 0.84. The AUCs for 3- and 5-year OS are the same and are 0.81, 0.83, and 0.81 in the training, validation, and overall cohorts, respectively. The AUCs for 3- and 5-year CSS are 0.78 and 0.80, 0.79 and 0.80, and 0.79 and 0.80 in those three cohorts. Conclusions: Our model shows the best prediction accuracy of the OS and CSS for patients with vulvar cancer (VC), which is of significant clinical practice value.

Radiotherapy Plus Chemotherapy Leads to Prolonged Survival in Patients With Anaplastic Thyroid Cancer Compared With Radiotherapy Alone Regardless of Surgical Resection and Distant Metastasis: A Retrospective Population Study.

Background: Whether anaplastic thyroid cancer (ATC) patients benefit more from radiotherapy plus chemotherapy (RCT) than from radiotherapy alone (RT) was controversial. We aimed to investigate the effectiveness of RCT versus RT on ATC overall and within subgroups by surgical resection and distant metastasis in a large real-world cohort. Methods: Patients with ATC diagnosed between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results Program database. Inverse probability weighting (IPW) was performed to balance variables between the two groups. Multivariate Cox proportional hazard model and Fine-Gray compete-risk model were carried out to investigate prognostic factors relating to overall survival (OS) and cancer-specific survival (CSS). Subgroup analysis was carried out, and a forest plot was graphed. Results: Of the 491 ATC patients, 321 (65.4%) were in the RCT group and 170 (34.6%) were in the RT group. The median OS was 4 months [interquartile range (IQR) 2-7] and 2 months (IQR 1-4) for patients in the RCT and RT groups, respectively. As indicated by the inverse probability weighting multivariate regression, RCT was associated with significantly improved OS (adjusted HR = 0.69, 95% CI = 0.56-0.85, p < 0.001) and CSS (adjusted subdistribution HR = 0.77, 95% CI = 0.61-0.96, p = 0.018). The prominent effect of RCT versus RT alone remains significant within each subgroup stratified by surgical resection and distant metastasis. Older age, single marital status, surgical resection, distant metastasis, and tumor extension were significant prognostic factors of survival. Conclusions: RCT contributes to prolonged OS and CSS compared with RT alone in ATC patients, regardless of surgical resection and distant metastasis. RCT should be preferentially applied to ATC patients.

Safety and Benefit Of Sentinel Lymph Nodes Biopsy Compared to Regional Lymph Node Dissection in Primary Vulvar Cancer Patients Without Distant Metastasis and Adjacent Organ Invasion: A Retrospective Population Study.

BACKGROUND: The safety and benefit of sentinel lymph node biopsy (SLNB) compared with regional lymph node dissection (RLND) and no lymph nodes removed (NA) in patients with vulvar squamous cell cancer (VSCC) was not well studied. METHODS: A retrospective analysis on VSCC patients without distant metastasis and adjacent organ invasion from the Surveillance, Epidemiology, and End Results Program database between 2004 and 2016 was carried out. Within subgroups stratified by negative (LN-) or positive (LN+) regional lymph node findings, inverse probability weighting (IPW) adjusted multivariate Fine-Gray compete risk (CR) model and accelerated failure time (AFT) model was used to investigate the factors associated with and cancer-specific survival (CSS) and overall survival (OS). RESULTS: Of the 3,161 VSCC patients treated with surgery, 287 (9.1%) underwent SLNB, 1,716 (54.3%) underwent RLND, and 1,158 (36.6%) had no regional lymph nodes removed. As illustrated by IPW adjusted multivariate regressions, SLNB was significantly associated with prolonged CSS (LN-, adjusted sub-proportional hazard ratio [sHR] = 0.42; 95% confidence interval [CI], 0.19-0.93; P=0.032; LN+, adjusted sHR = 0.29; 95% CI, 0.16-0.54, P<0.001) and OS (LN-, adjusted time ratio [TR] = 1.38; 95% CI, 0.82-2.32; P=0.226; LN+, adjusted TR = 2.68; 95% CI, 1.73-4.14; P<0.001), although the effect of SLNB on OS was not significant within the LN- cohort. Moreover, SLNB led to improved CSS (adjusted sHR = 0.40; 95% CI, 0.23-0.70; P = 0.001) and OS (adjusted TR=1.15, 95% CI 0.76-1.73, P=0.279) compared with NA. Age was a significant prognostic factor of CSS and OS, whereas tumor size, surgery type, and invasion depth were not. CONCLUSIONS: SLNB leads to significantly prolonged CSS and OS in VSCC surgery patients without distant metastasis and adjacent organ invasion than RLND, except for the similar OS in the LN- cohort. SLNB could be carried out preferentially for VSCC surgery patients without distant metastasis and adjacent organ invasion, irrespective of tumor size, surgery type, invasion depth, and regional lymph nodes metastasis. Further prospective clinical trials are warranted to confirm the findings of this study.