Objective: Increased expression of programmed death-ligand 1 (PD-L1) on tumor cells can be found in various malignancies; however, very limited information is known about its role in anal squamous cell carcinoma (ASCC). This study explored PD-L1 expression in ASCC patients and its association with patients' clinicopathological features, CD8+ T cell infiltration, and prognosis. Methods: Formalin-fixed paraffin- embedded tumor samples from 26 patients with ASCC were retrieved. The levels of PD-L1 expression on the membrane of both tumor cells and tumor-infiltrating mononuclear cells (TIMCs) were evaluated by immunohistochemistry. CD8+ T cell densities, both within tumors and at the tumor-stromal interface, were also analyzed. Baseline clinicopathological characteristics, human papilloma virus (HPV) status, and outcome data correlated with PD-L1-positive staining. Results: PD-L1 expression on tumor cells and TIMCs was observed in 46% and 50% of patients, respectively. Nineteen patients (73%) were HPV positive, with 7 showing PD-L1-positive staining on tumor cells and 9 showing PD-L1-positive staining on TIMCs. Increasing CD8+ density within tumors, but not immune stroma, was significantly associated with decreased PD-L1 expression by both tumor cells and TIMCs (P=0.0043 and P=0.0007). Patients with negative PD-L1 expression had significantly better progression-free survival (P=0.038 and P=0.0443) and a non-statistically significant trend toward longer overall survival (P=0.0882 and P=0.1222) compared with patients with positive PD-L1 expression. Conclusion: PD-L1 is widely expressed on the membrane of tumor cells and TIMCs in ASCCs. Its negative impact on prognosis may be due to the diminished CD8+ T cell infiltration within tumors.
Non-small cell lung cancer (NSCLC) prognosis and risk of lymph node positivity (LN+) are reference points for reasonable treatments. The aim of the current study was to investigate the effect of age on LN+ and NSCLC death. Data from the Surveillance, Epidemiology, and End Results (SEER) registry were used to identify 82,253 patients with NSCLC diagnosed between 1988 and 2008. All the patients underwent standard lung cancer surgery with lymph node examination. Demographic and clinicopathological parameters were extracted and compared among each age group. Impact of age on LN+ and NSCLC death was evaluated by the Cochran-Armitage trend test and logistic univariate and multivariate analyses for all T stages. Overall, 22,711 (27.60%) patients of the entirety had lymph node metastasis and 28,968 (35.22%) patients died of NSCLC within 5 years. With the increase in age, LN+ rates decreased regardless of T stages (P<0.001), whereas NSCLC-specific mortality increased in stages T1-T3 (P<0.001). Controlling other covariates in multivariable logistic regression, age remained an independent risk factor for LN+ in all T stages (P<0.05) and in stages T1-T3 (P<0.05). Our SEER analysis demonstrated a higher rate of LN+ and lower mortality in younger patients with NSCLC, after accounting for other covariates.
Purpose: It is well demonstrated that being married is associated with a better prognosis in multiple types of cancer. However, whether the protective effect of marital status varied across race/ethnicity and gender in patients with hepatocellular carcinoma remains unclear. Therefore, we aimed to evaluate the roles of race/ethnicity and gender in this relationship. Patients and methods: We identified eligible patients from Surveillance, Epidemiology and End Results (SEER) database during 2004-2012. Overall and cancer-specific survival differences across marital status were compared by Kaplan-Meier curves. We also estimated crude hazard ratios (CHRs) and adjusted hazard ratios (AHRs) with 95% confidence intervals (CIs) for marital status associated with survival by race/ethnicity and gender in Cox proportional hazard models. Results: A total of 12,168 eligible patients diagnosed with hepatocellular carcinoma were included. We observed that married status was an independent protective prognostic factor for overall and cancer-specific survival. In stratified analyses by race/ethnicity, the AHR of overall mortality (unmarried vs married) was highest for Hispanic (AHR = 1.25, 95% CI, 1.13-1.39; P<0.001) and lowest for Asian or Pacific Islander (AHR = 1.13; 95% CI, 1.00-1.28; P=0.042). Stratified by gender, the AHR was higher in males (AHR = 1.27; 95% CI, 1.20-1.33; P<0.001). Conclusion: We demonstrated that married patients obtained better survival advantages. Race/ethnicity and gender could influence the magnitude of associations between marital status and risk of mortality.
Esophageal cancer (EC) is an extremely aggressive, lethal malignancy that is increasing in incidence worldwide. At present, definitive chemoradiotherapy is accepted as the standard treatment for locally advanced EC. The EC guidelines recommend a radiation dose of 50.4 Gy for definitive treatment, yet the outcomes for patients who have received standard-dose radiotherapy remain unsatisfactory. However, some studies indicate that a higher radiation dose could improve local tumor control, and may also confer survival benefits. Some studies, however, suggest that high-dose radiotherapy does not bring survival benefit. The available data show that most failures occurred in the gross target volume (especially in the primary tumor) after definitive chemoradiation. Based on those studies, we hypothesize that at least for some patients, more intense local therapy may lead to better local control and survival. The aim of this review is to evaluate the radiation dose, fractionation strategies, and predictive factors of response to therapy in functional imaging for definitive chemoradiotherapy in esophageal carcinoma, with an emphasis on seeking the predictive model of response to CRT and trying to individualize the radiation dose for EC patients.
Background: The prognosis of pancreatic carcinoma (PC) remains poor and the American Joint Committee on Cancer (AJCC) 8th staging system for survival prediction in PC patients after curative resection is still limited. Thus, the aim of this study is to refine a valuable prognostic model and novel staging system for PC with curative resection. Methods: The data of 3,458 patients used in this study were retrieved from the Surveillance, Epidemiology, and End Results database registry of National Cancer Institute. The prognostic value of lymph node ratio (LNR) was analyzed in the primary cohort and prognostic nomogram based on the LNR was established to create a novel staging system. Then, analyses were conducted to evaluate the application of the formulated nomogram staging system and the AJCC 8th staging system. The predictive performance of model was further validated in the internal validation cohort. Results: Significant positive correlations were found between LNR and all factors except for surgical procedures. The results of univariate and multivariate analyses showed that LNR was identified as an independent prognostic indicator for overall survival (OS) in both primary and validation cohorts (all P < 0.001). A prognostic nomogram based on the LNR was formulated to obtain superior discriminatory abilities. Compared with the AJCC 8th staging system, the formulated nomogram staging system showed higher hazard ratios of stage II, III, and IV disease (reference to stage I disease) that were 1.637, 2.300, and 3.521, respectively, by univariate analyses in the primary cohort and the distinction between stage I, II, and III disease at the beginning or end of the survival curves was more apparent. All these results were further verified in the validation cohort. Conclusion: LNR can be considered as a useful independent prognostic indicator for PC patients after curative resection regardless of the surgical procedures. Compared with the AJCC 8th staging system, the formulated nomogram showed superior predictive accuracy for OS and its novel dstaging system revealed better risk stratification.
Background: The purpose of this study was to clarify whether pretreatment tumor burden-related index, including the gross tumor volume (GTV) of metastatic lymph nodes (V-LN) and maximum diameter of metastatic lymph nodes (D-LN), and inflammatory markers, consisting of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), are useful for assessing the therapeutic effects and prognosis with secondary lymph node metastasis (LNM) receiving chemoradiotherapy (CRT) or radiotherapy (RT) alone after resection of esophageal squamous cell carcinoma (ESCC). Patients and methods: A total of 119 patients with secondary LNM after resection of ESCC were recruited and received curative RT only or CRT. The enrolled patients were grouped according to the median values of NLR, PLR, V-LN, and D-LN. The relationship between the responsiveness to treatment and these markers was analyzed by logistic analysis. The Kaplan-Meier method and log-rank test were adopted to calculate and compare the overall survival (OS) rates with these markers. The Cox models were used to carry out multivariate analyses. Results: Univariate logistic regression analysis showed that the responses to treatment were highly associated with treatment method (P=0.011), NLR (P=0.000), PLR (P=0.003), V-LN (P=0.000), and D-LN (P=0.000). Next, multivariate logistic regression analysis showed that therapeutic method (hazard ratio [HR]=1.225, P=0.032), NLR (HR=2.697, P=0.019), and V-LN (HR=4.607, P=0.034) were independent risk factors for tumor response. Additionally, Kaplan-Meier survival analysis of this cohort revealed that NLR (chi(2)=27.298, P=0.000), PLR (chi(2)=16.719, P=0.000), V-LN (chi(2)=48.823, P=0.000), D-LN (chi(2)=40.724, P=0.000), and treatment methods (chi(2)=18.454, P=0.018) were significantly associated with OS. Furthermore, multivariate analysis was performed, and the results showed that therapeutic method (HR=1.223, P=0.048), NLR (HR=2.000, P=0.018), V-LN (HR=2.379, P=0.020), and D-LN (HR=2.901, P=0.002) were considered independent prognostic factors for OS. Conclusion: This study found that NLR and V-LN were promising as predictive markers for therapeutic effects, and NLR combined with V-LN and with D-LN might be useful biomarkers in predicting outcomes in patients with secondary LNM receiving CRT or single RT after esophagectomy.
Colorectal cancer is one of the most common human malignant tumors. Recent research has shown that colorectal cancer is a dysbacteriosis-induced disease; however, the role of intestinal bacteria in colorectal cancer is unclear. This review explores the role of intestinal flora in colorectal cancer. In total, 57 articles were included after identification and screening. The pertinent literature on floral metabolites in colorectal cancer from three metabolic perspectives - including carbohydrate, lipid, and amino acid metabolism - was analyzed. An association network regarding the role of intestinal flora from a metabolic perspective was constructed by analyzing the previous literature to provide direction and insight for further research on intestinal flora in colorectal cancer.
Background: The hypermethylation of APC gene is observed in various cancers, including esophageal cancer (EC). However, the association between APC methylation and the initiation and progression of EC is poorly understood. Purpose and methods: The current study systematically reviewed studies on abnormal methylation of APC in EC and quantitatively synthesized 18 studies by meta-analysis involving 1008 ECs, 570 Barrett's esophagus (BE), and 782 controls. Results: Our results showed higher methylation of APC in EC (OR = 23.33, P < 0.001) and BE (OR = 9.34, P < 0.001) than in normal controls. Whereas APC methylation in EC was similar to that in BE (P = 0.052), it was not associated with tumor stage (P = 0.204). Additionally, APC methylation was not significantly associated with overall survival (OS) and relapse-free survival (RFS) in patients with EC. The performance of APC methylation for the detection of EC and BE achieved areas under the receiver operating characteristic curves of 0.94 and 0.88, respectively. Conclusion: Our results imply that APC methylation detection is a potential diagnostic bio-marker for EC and BE.
Adrenal myelolipoma with hyperandrogenemia is extremely rare. We report a case of a 26-year-old Chinese female with schizophrenia, who presented with a hormonally active tumor causing hyperandrogenemia. The mass was found by computerized tomography when she had her gynecologic examination for secondary amenorrhea, and it was confirmed to be an adrenal myelolipoma after a histopathological study. She was referred for a left adrenal laparoscopic excision, and the size of adrenal myelolipoma was found to be more than 10 cm. We report this case because large adrenal myelolipomas with hyperandrogenemia and schizophrenia are rare, and adrenal myelolipoma associated with hyperandrogenemia might be determined by the enzymes involved in the production of hormones.
Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues of digestive systems and mediate specific uptake of small molecule substrates in facilitative manner. Given the important role of SLC proteins in maintaining normal functions of digestive system, dysregulation of these protein in digestive system neoplasms may deliver biological and clinical significance that deserves systemic studies. In this review, we critically summarized the recent advances in understanding the role of SLC proteins in digestive system neoplasms. We highlighted that several SLC subfamilies, including metal ion transporters, transporters of glucose and other sugars, transporters of urea, neurotransmitters and biogenic amines, ammonium and choline, inorganic cation/anion transporters, transporters of nucleotide, amino acid and oligopeptide organic anion transporters, transporters of vitamins and cofactors and mitochondrial carrier, may play important roles in mediating the initiation, progression, metastasis, and chemoresistance of digestive system neoplasms. Proteins in these SLC subfamilies may also have diagnostic and prognostic values to particular cancer types. Differential expression of SLC proteins in tumors of digestive system was analyzed by extracting data from human cancer database, which revealed that the roles of SLC proteins may either be dependent on the substrates they transport or be tissue specific. In addition, small molecule modulators that pharmacologically regulate the functions of SLC proteins were discussed for their possible application in the treatment of digestive system neoplasms. This review highlighted the potential of SLC family proteins as drug target for the treatment of digestive system neoplasms.
Introduction: Breast cancer is the most common cancer in women worldwide. The association between body mass index (BMI) and breast cancer risk has been paid more attention in the past few years, but the findings are still controversial. To obtain a more reliable conclusion, we performed a dose-response meta-analysis on 12 prospective cohort studies comprising 22,728,674 participants. Methods: Linear and nonlinear trend analyses were conducted to explore the dose-response relationship between BMI and breast cancer risk. The summary relative risk (SRR) and 95% confidence intervals (CIs) were used to evaluate the cancer risk. Results: The overall results showed a weak positive association between a 5-unit increase in BMI and breast cancer risk, indicating that a 5 kg/m(2) increase in BMI corresponded to a 2% increase in breast cancer risk (SRR: 1.02, 95% CI: 1.01-1.04, p<0.001). Notably, further subgroup meta-analysis found that higher BMI could be a protective factor of breast cancer risk for premenopausal women (SRR: 0.98, 95% CI: 0.96-0.99, p<0.001). In addition, the dose-response result demonstrated that there was a linear association between BMI and breast cancer risk (P-nonlinearity = 0.754). Conclusion: In summary, this dose-response meta-analysis of prospective cohort studies showed that every 5 kg/m(2) increase in BMI corresponded to a 2% increase in breast cancer risk in women. However, higher BMI could be a protective factor in breast cancer risk for premenopausal women. Further studies are necessary to verify these findings and elucidate the pathogenic mechanisms.
Background: The AURA3 clinical trial has shown that advanced non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations in circulating tumor DNA (ctDNA) could benefit from osimertinib. Purpose: The aim of this study was to assess the usefulness of QuantStudio (TM) 3D Digital PCR System platform for the detection of plasma EGFR T790M mutations in NSCLC patients, and compare the performances of 3D Digital PCR and ARMS-PCR. Patients and methods: A total of 119 Chinese patients were enrolled in this study. Mutant allele frequency of plasma EGFR T790M was detected by 3D Digital PCR, then 25 selected samples were verified by ARMS-PCR and four of them were verified by next generation sequencing (NGS). Results: In total, 52.94% (69/119) had EGFR T790M mutations detected by 3D Digital PCR. In 69 positive samples, the median mutant allele frequency (AF) was 1.09% and three cases presented low concentration (AF <0.1%). Limited by the amount of plasma DNA, 17 samples (AF <2.5%) and eight samples (T790M-) were selected for verification by ARMS-PCR. Four of those samples were verified by NGS as a third verification method. Among the selected 17 positive cases, ten samples presented mutant allele frequency <0.5%, and seven samples presented intermediate mutant allele frequency (0.5% AF 2.5%). However, only three samples (3/17) were identified as positive by ARMS-PCR, namely, P6 (AF = 1.09%), P7 (AF = 2.09%), and P8 (AF = 2.21%). It is worth mentioning that sample P9 (AF = 2.05%, analyzed by 3D Digital PCR) was identified as T790M-by ARMS-PCR. Four samples were identified as T790M+ by both NGS and 3D Digital PCR, and typically three samples (3/4) presented at a low ratio (AF <0.5%). Conclusion: Our study demonstrated that 3D Digital PCR is a novel method with high sensitivity and specificity to detect EGFR T790M mutation in plasma.
Background: According to recent clinical observations, deficient DNA mismatch repair (dMMR) is capable of improving antitumor effects of the PD-1/PD-L1 pathway, suggesting that dMMR may act as a prognostic indicator of PD-1/PD-L1 antibody drugs. In this study, we examined the dMMR and PD-1/PD-L1 expression, as well as explored the correlation of dMMR status with PD-1/PD-L1 expression in cervical cancer patients, in order to optimize cervical cancer patient selection for PD-1/PD-L1 antibody drug treatment, which is helpful to avoid adverse effects and keep costs manageable. Methods: Sixty-six tissue samples from patients with squamous cell carcinoma were collected, and data of their clinical characteristics were also gathered. Based on these samples, the expression levels of MLH1, MSH2, and PD-L1 in cancer cells were tested by immunohistochemical assay (IHC). Moreover, PD-1/PD-L1 expression in tumor-invading lymphocytes (TILs) was detected by IHC as well. Six single-nucleotide-repeat markers of microsatellite instability (MSI), including NR-27, MONO-27, BAT-25, NR-24, NR-21, and BAT-26, were tested by capillary electrophoresis sequencer analysis. According to expression of MLH1, MSH2 and the MSI test, all 66 cases were divided into dMMR or proficient DNA mismatch repair (pMMR) groups. The comparisons of dMMR and PD-L1 in cancer cells and of PD-1/PD-L1 in TILs were conducted categorized by age, childbearing history, history of abortion, ethnicity, and cancer cell differentiation subgroup. Furthermore, PD-L1 levels in cancer cells and PD-1/PD-L1 in TILs were analyzed and compared in both dMMR and pMMR subgroups. Results: Of the patient samples, 25.8% were associated with dMMR. PD-L1 in cancer cells, PD-L1 in TILs, and PD-1 in TILs took up 59.1%, 47.0%, and 60.6%, respectively. The data indicated that both dMMR and PD-L1 overexpression resulted from lower cancer differentiation, more incidences of childbearing, and a history of abortion. Abortion could significantly increase PD-1 expression levels in TILs. Additionally, more incidence of childbearing or older age (35-55 years) was able to upregulate PD-L1 expression in TILs. Statistical difference of PD-L1 in cancer cells could be observed between dMMR and pMMR subgroups. In the dMMR group, PD-L1 in cancer cells and PD-1 in TILs had no correlation (r(s) = 0.161, p=0.537), but in the pMMR group, they had good correlation (r(s) = 0.645, p<0.001). Conclusion: According to prior studies and our own experiments, PD-L1 in both cancer cells and TILs and PD-1 in TILs are widely observed in cervical cancer patients, indicating that there may be potential to apply PD-1/PD-L1 antibody drugs in cervical cancer. dMMR patients are associated with higher PD-L1 expression compared with pMMR ones, which suggested that PD-1/PD-L1 antibody drugs may work well in dMMR cervical cancer patients. Moreover, in patients with more incidences of childbearing or abortion, dMMR may be a molecular detection target for clinical application of PD-1/PD-L1 antibody drugs.
Background: Recent studies have indicated that the C-reactive protein/albumin (CRP/ALB) ratio (CAR) may represent a simple inflammation-based index for assessing the host inflammatory response. In this study, the prognostic value of the CAR for distant metastasis-free survival (DMFS) in nasopharyngeal carcinoma (NPC) was assessed. Methods: A total of 1,168 non-metastatic NPC patients from Sun Yat-sen University Cancer Center were retrospectively included. The optimal cutoff value for CAR was defined by the Cutoff Finder online tool. Propensity case-matched analysis was performed to adjust for potential differences in baseline characteristics. Subsequently, the prognostic value of the CAR for DMFS was validated in a 756 validation cohort with NPC. Results: The optimal CAR cutoff value was 0.081. Patients with high CAR values had significantly poorer DMFS than those with low CAR in univariate and multivariate analyses before propensity score matching. The CAR could also significantly stratify patients into different risks of developing distant metastasis in subgroup analysis. Propensity score analyses showed that CAR remained a prognostic factor for DMFS, thus excluding other interpretations and selection bias. Moreover, the prognostic value of the CAR was robustly confirmed in the external validation cohort. Conclusion: CAR is an inexpensive and easy-to-measure inflammatory index that may aid clinicians in the development of individualized treatment and follow-up strategies for patients with non-metastatic NPC.
Objectives: Surgical resection remains a controversial treatment for hepatocellular carcinoma (HCC) within different Barcelona Clinic Liver Cancer (BCLC) stages. The objective of this study was to evaluate the long-term outcome of patients undergoing surgical resection (SR) compared to non-surgical treatments across different BCLC stages. Patients and methods: One thousand four hundred forty-three HCC patients within BCLC 0, A, B and C stages were identified. Overall survival was compared by log-rank test among patients within different BCLC stages and among patients receiving different treatments (SR vs locoregional therapy [LRT] vs best supportive care). Propensity score matching analysis was introduced to mitigate the confounding biases between the groups. Results: The median survival time of the patients diminished from early, intermediate to advanced BCLC stages (BCLC 0-A 43 [range 0-100] months vs BCLC B 32 [range 0-100] months vs BCLC C 27 [range 0-90] months, all p<0.05). Patients undergoing SR presented with better liver function and more favorable tumor status and, consequently, displayed significant better overall survival than patients receiving LRT or best supportive care at different BCLC stages. In adjusted cohort after propensity score matching, patients who were surgically treated consistently had more favorable outcome than those who were non-curatively treated across different BCLC stages (median survival [range]: BCLC stage B: resection 45 [0-100] months vs LRT 36 [0-81] months, p=0.002; BCLC stage C: resection 39 [3-77] months vs LRT 27 [0-54] months, p=0.003). Conclusion: Surgical resection should be considered as a radical treatment for selected HCC patients regardless of the BCLC stages when appropriate.