HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients

HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The HLA-G gene shows several polymorphisms involved in mRNA and protein levels. We decided to study the implication of two polymorphisms (rs371194629; 14bp INS/DEL and rs1063320; +3142 C/G) in paired tissue samples (tumoral and non-tumoral) from 107 Spanish patients with gastric adenocarcinoma and 58 healthy control individuals, to assess the possible association of the HLA-G gene with gastric adenocarcinoma susceptibility, disease progression and survival. The presence of somatic mutations involving these polymorphisms was also analyzed. The frequency of the 14bp DEL allele was increased in patients (70.0%) compared to controls (57.0%, p=0.025). In addition, the haplotype formed by the combination of the 14bp DEL/+3142 C variants is also increased in patients (54.1% vs 44.4%, p=0.034, OR=1.74 CI95% 1.05-2.89). Kaplan-Meier analysis revealed that 14bp DEL/DEL patients showed lower 5-year life-expectancy than INS/DEL or INS/INS (p=0.041). Adjusting for TNM staging (Cox regression analysis) disclosed a significant difference in death risk (p=0.03) with an expected hazard 2.6 times higher. Finally, no somatic mutations were found when comparing these polymorphisms in tumoral vs non-tumoral tissues, which indicates that this is a preexisting condition in patients and not a de novo, tumor-restricted, event. In conclusion, the variants predominant in patients were those increasing HLA-G mRNA stability and HLA-G expression, clearly involving this molecule in gastric adenocarcinoma susceptibility, disease progression and survival and making it a potential target for immunotherapeutic approaches.

Download Full-text

Increased RCAS1 Expression Is Associated with Advanced Histopathological Stage and Poor Prognosis in Patients with Gastric Adenocarcinoma

Disease Markers ◽

10.1155/2013/527548 ◽

2013 ◽

Vol 35 ◽

pp. 213-219 ◽

Cited By ~ 4

Author(s):

Constantinos Giaginis ◽

Themistoclis Efkarpidis ◽

Paraskevi Alexandrou ◽

Efstratios Patsouris ◽

Gregory Kouraklis ◽

...

Keyword(s):

Gastric Adenocarcinoma ◽

Cox Regression ◽

Human Tumor ◽

Clinicopathological Parameters ◽

Rank Test ◽

Survival Times ◽

Biological Behaviour ◽

Tissue Samples ◽

Cox Regression Analysis ◽

Expression Levels

Background. The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that has been considered to play a crucial role in tumor progression by enabling cancer cells to evade immune surveillance. The present study aimed to evaluate the clinical significance of the RCAS1 expression in gastric adenocarcinoma.Material and Methods. RCAS1 protein expression was assessed immunohistochemically on 54 gastric adenocarcinoma tissue samples and was analyzed in relation to clinicopathological parameters, tumor proliferative capacity, and patients’ survival.Results. Enhanced RCAS1 expression levels were significantly associated with advanced histopathological stage and presence of organ metastasis (P=0.0084andP=0.0327). Gastric cancer patients with elevated RCAS1 expression levels showed significantly shorter survival times compared to those with low RCAS1 expression (log-rank test,P=0.0168). In multivariate analysis, histopathological stage and grade of differentiation as well as the RCAS1 expression were identified as independent prognostic factors (Cox regression analysis,P=0.0204,P=0.0035, andP=0.0081).Conclusions. Our data support the evidence that RCAS1 upregulation may contribute to gastric malignant progression, representing a useful biomarker to predict the biological behaviour and prognosis in gastric neoplasia.

Download Full-text

Survival analysis of patients with stage T2a and T2b perihilar cholangiocarcinoma treated with radical resection

10.21203/rs.3.rs-22931/v1 ◽

2020 ◽

Author(s):

Jian Zhao ◽

Wei Zhang ◽

Jun Zhang ◽

Yi Zhang ◽

Wenjie Ma ◽

...

Keyword(s):

Cox Regression ◽

Staging System ◽

Predictive Performance ◽

Radical Resection ◽

Tnm Staging ◽

Perihilar Cholangiocarcinoma ◽

Curative Intent ◽

Cox Regression Analysis ◽

Significant Difference ◽

8Th Edition

Abstract Background: Both the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) for perihilar cholangiocarcinoma (pCCA) had the same definition for T2a and T2b. But the value of this classification as prognostic factors remains unclear. Methods: 178 patients with stage T2a or T2b who underwent curative intent resection for pCCA between Jan 2010 and Dec 2018 were enrolled. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate Cox regression analysis. The overall survival (OS) were calculated by Kaplan-Meier method.Results: There was no significant difference in OS between T2a and T2b group. The median OS were 37 and 31 months (P=0.354). Both the 7th and 8th edition of the AJCC TNM staging demonstrated a poor prognostic predictive performance. High level of AST (≥85.0IU/L) and CA19-9 (≥1000 U/mL), vascular resection and lower pathological differentiation of the tumor were the independent predictors for poor survival after resection.Conclusion: The newly released 8th edition of AJCC staging system demonstrated a poor ability to discriminate the prognosis of patients with stage T2a and T2b after resection for pCCA.

Download Full-text

Survival analysis of patients with stage T2a and T2b perihilar cholangiocarcinoma treated with radical resection

10.21203/rs.3.rs-22931/v3 ◽

2020 ◽

Author(s):

Jian Zhao ◽

Wei Zhang ◽

Jun Zhang ◽

Yi Zhang ◽

Wenjie Ma ◽

...

Keyword(s):

Cox Regression ◽

Staging System ◽

Tnm Staging ◽

Perihilar Cholangiocarcinoma ◽

Curative Intent ◽

Cox Regression Analysis ◽

Significant Difference ◽

Ajcc Staging System ◽

Ajcc Staging ◽

8Th Edition

Abstract Background: Both the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (pCCA) had the same definition for T2a and T2b. But the value of this classification as prognostic factor remains unclear. Methods: 178 patients with stage T2a or T2b who underwent curative intent resection for pCCA between Jan 2010 and Dec 2018 were enrolled. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate Cox regression analysis. The overall survival (OS) were calculated by Kaplan-Meier method.Results: There was no significant difference in OS between T2a and T2b groups，and the median OS duration were 37 and 31 months (P=0.354). Both the 7th and 8th edition of the AJCC TNM staging demonstrated a poor prognostic predictive performance. High level of preoperative AST (≥85.0IU/L) and CA19-9 (≥1000 U/mL), vascular resection and lower pathological differentiation of the tumor were the independent predictors for poor survival after resection.Conclusion: The newly released 8th edition of AJCC staging system demonstrated a poor ability to discriminate the prognosis of patients with stage T2a and T2b pCCA after resection.

Download Full-text

Survival analysis of patients with stage T2a and T2b perihilar cholangiocarcinoma treated with radical resection

10.21203/rs.3.rs-22931/v2 ◽

2020 ◽

Author(s):

Jian Zhao ◽

Wei Zhang ◽

Jun Zhang ◽

Yi Zhang ◽

Wenjie Ma ◽

...

Keyword(s):

Cox Regression ◽

Staging System ◽

Tnm Staging ◽

Perihilar Cholangiocarcinoma ◽

Curative Intent ◽

Cox Regression Analysis ◽

Significant Difference ◽

Ajcc Staging System ◽

Ajcc Staging ◽

8Th Edition

Download Full-text

Predictive Model for Live Birth at 12 Months After Starting In-Vitro Fertilization Treatment

MedPharmRes ◽

10.32895/ump.mpr.2.2.5 ◽

2018 ◽

Vol 2 (2) ◽

pp. 5-20

Author(s):

Vu Ho ◽

Toan Pham ◽

Tuong Ho ◽

Lan Vuong

Keyword(s):

In Vitro Fertilization ◽

Live Birth ◽

Cox Regression ◽

Financial Burden ◽

Oocyte Retrieval ◽

Operating Characteristics ◽

Vitro Fertilization ◽

Cox Regression Analysis ◽

Significant Difference

IVF carries a considerable physical, emotional and financial burden. Therefore, it would be useful to be able to predict the likelihood of success for each couple. The aim of this retrospective cohort study was to develop a prediction model to estimate the probability of a live birth at 12 months after one completed IVF cycle (all fresh and frozen embryo transfers from the same oocyte retrieval). We analyzed data collected from 2600 women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) at a single center in Vietnam between April 2014 and December 2015. All patients received gonadotropin-releasing hormone (GnRH) antagonist stimulation, followed by fresh and/or frozen embryo transfer (FET) on Day 3. Using Cox regression analysis, five predictive factors were identified: female age, total dose of recombinant follicle stimulating hormone used, type of trigger, fresh or FET during the first transfer, and number of subsequent FET after the first transfer. The area under the receiver operating characteristics curve for the final model was 0.63 (95% confidence interval [CI] 0.60‒0.65) and 0.60 (95% CI 0.57‒0.63) for the validation cohort. There was no significant difference between the predicted and observed probabilities of live birth (Hosmer-Lemeshow test, p > 0.05). The model developed had similar discrimination to existing models and could be implemented in clinical practice.

Download Full-text

The prognostic and diagnostic significance of the neutrophil-to-lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study

British Journal of Cancer ◽

10.1038/s41416-021-01445-3 ◽

2021 ◽

Author(s):

Philip J. Johnson ◽

Sofi Dhanaraj ◽

Sarah Berhane ◽

Laura Bonnett ◽

Yuk Ting Ma

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Prognostic Factor ◽

Cox Regression ◽

Prognostic Models ◽

Controlled Study ◽

Cox Regression Analysis ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Significant Difference

Abstract Background The neutrophil–lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC). Methods In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis. Results On entry into the study (‘baseline’), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage. Conclusion NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.

Download Full-text

Single modality radical radiotherapy is an acceptable alternative for the older patient with squamous cell carcinoma of the oesophagus

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2020-000492 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000492

Author(s):

Sarah Derby ◽

Matthew Forshaw ◽

Caroline Lowrie ◽

Derek Grose ◽

Husam Marashi ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cox Regression ◽

Multimodality Treatment ◽

Radical Radiotherapy ◽

Older Patient ◽

Older Population ◽

Cox Regression Analysis ◽

Significant Difference

BackgroundOesophageal cancer remains a common cause of cancer mortality worldwide. Increasingly, oncology centres are treating an older population and comorbidities may preclude multimodality treatment with chemoradiotherapy (CRT). We review outcomes of radical radiotherapy (RT) in an older population treating squamous cell carcinoma (SCC) oesophagus.MethodsPatients over 65 years receiving RT for SCC oesophagus between 2013 and 2016 in the West of Scotland were identified. Kaplan-Meier and Cox-regression analysis were used to compare overall survival (OS) between patients treated with radical RT and radical CRT.ResultsThere were 83 patients over 65 years treated with either RT (n=21) or CRT (n=62). There was no significant difference in median OS between CRT versus RT (26.8 months vs 28.5 months, p=0.92). All patients receiving RT completed their treatment whereas 11% of CRT patients did not complete treatment.ConclusionSurvival in this non-trial older patient group managed with CRT is comparable to that reported in previous trials. RT shows better than expected outcomes which may reflect developments in RT technique. This review supports RT as an alternative in older patients, unfit for concurrent treatment.

Download Full-text

Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada

Cancers ◽

10.3390/cancers13112844 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2844

Author(s):

Christopher J. D. Wallis ◽

Bobby Shayegan ◽

Scott C. Morgan ◽

Robert J. Hamilton ◽

Ilias Cagiannos ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Clinical Decision Making ◽

Cox Regression ◽

De Novo ◽

Population Based ◽

Population Based Study ◽

Cox Regression Analysis ◽

Lymphocyte Ratio ◽

Laboratory Markers

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan–Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71–83). The median survival was 18 months (IQR: 10–31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

Download Full-text

Impact of Hybrid Operating Rooms on Long-Term Clinical Outcomes Following Fenestrated and Branched Endovascular Aortic Repair

Journal of Endovascular Therapy ◽

10.1177/1526602821996725 ◽

2021 ◽

pp. 152660282199672

Author(s):

Giovanni Tinelli ◽

Marie Bonnet ◽

Adrien Hertault ◽

Simona Sica ◽

Gian Luca Di Tanna ◽

...

Keyword(s):

Operating Room ◽

Clinical Outcomes ◽

Cox Regression ◽

Statistical Significance ◽

Aortic Aneurysms ◽

Study Patient ◽

Cox Regression Analysis ◽

Significant Difference ◽

The Impact

Purpose: Evaluate the impact of hybrid operating room (HOR) guidance on the long-term clinical outcomes following fenestrated and branched endovascular repair (F-BEVAR) for complex aortic aneurysms. Materials and Methods: Prospectively collected registry data were retrospectively analyzed to compare the procedural, short- and long-term outcomes of consecutive F-BEVAR performed from January 2010 to December 2014 under standard mobile C-arm versus hybrid room guidance in a high-volume aortic center. Results: A total of 262 consecutive patients, including 133 patients treated with a mobile C-arm equipped operating room and 129 with a HOR guidance, were enrolled in this study. Patient radiation exposure and contrast media volume were significantly reduced in the HOR group. Short-term clinical outcomes were improved despite higher case complexity in the HOR group, with no statistical significance. At a median follow-up of 63.3 months (Q1 33.4, Q3 75.9) in the C-arm group, and 44.9 months (Q1 25.1, Q3 53.5, p=0.53) in the HOR group, there was no statistically significant difference in terms of target vessel occlusion and limb occlusion. When the endograft involved 3 or more fenestrations and/or branches (complex F-BEVAR), graft instability (36% vs 25%, p=0.035), reintervention on target vessels (20% vs 11%, p=0.019) and total reintervention rates (24% vs 15%, p=0.032) were significantly reduced in the HOR group. The multivariable Cox regression analysis did not show statistically significant differences for long-term death and aortic-related death between the 2 groups. Conclusion: Our study suggests that better long-term clinical outcomes could be observed when performing complex F-BEVAR in the latest generation HOR.

Download Full-text

Assessment of the value of adjuvant radiotherapy for treatment of gastric adenocarcinoma based on pattern of post-surgical progression

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02304-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Peng Wang ◽

Haihua Zhou ◽

Gaohua Han ◽

Qingtao Ni ◽

Shengbin Dai ◽

...

Keyword(s):

Local Recurrence ◽

Gastric Adenocarcinoma ◽

Adjuvant Radiotherapy ◽

Cox Regression ◽

Radical Resection ◽

Progression Rate ◽

Cox Regression Analysis ◽

T Stage ◽

Local Progression ◽

Degree Of Differentiation

Abstract Purpose To assess the value of adjuvant radiotherapy for treatment of gastric adenocarcinoma and to investigate subgroups of patients suitable for adjuvant radiotherapy. Methods and materials Data from 785 patients with gastric adenocarcinoma who had undergone D1/D2 radical resection and adjuvant chemotherapy were collected, the site of first progression was determined, and the relationship between the rate of local recurrence and clinicopathologic features was analyzed. Results By the end of the follow-up period, progression was observed in 405 patients. Local recurrence was observed as the first progression in 161 cases. The local recurrence rate was significantly lower than the non-local progression rate (20.5% vs 31.5%, p=0.007). Multivariate Cox regression analysis showed a significant relationship among degree of differentiation, T stage, N stage, and rate of local recurrence. Conclusions Not all patients with gastric carcinoma required adjuvant radiotherapy. However, patients with poorly differentiated cancer cells, advanced T stage (T3/T4), and positive lymph nodes, which included patients in the T4N1-2M0 subgroup, were recommended for adjuvant radiotherapy.

Download Full-text