scholarly journals Clinical impact of abdominal versus mediastinal metastases as a prognostic factor for poor outcomes following esophageal cancer surgery: a retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yutaka Miyawaki ◽  
Hiroshi Sato ◽  
Shuichiro Oya ◽  
Hirofumi Sugita ◽  
Yasumitsu Hirano ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Regression Analysis ◽  
Lymph Node ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Systemic Recurrence ◽  
Significant Difference

Abstract Background Surgery is still the mainstay of radical treatment for resectable esophageal cancer (EC). It is apparent that the presence or spread of lymph node metastasis (LNM) is a powerful prognostic factor in patients with EC who are eligible for curative treatment. Although the importance and efficacy of lymph node dissection in radical esophagectomy have been reported, the clinical or prognostic relevance of specific metastatic patterns within the mediastinal cavity and abdomen remains unclear. Methods We retrospectively analyzed the association of postoperative survival with clinical mediastinal LNM (cMLNM) and abdominal LNM (cALNM) in 157 patients who underwent radical EC surgery at our hospital between May 2012 and March 2018. Results A significant difference in cause-specific survival (CSS) was observed between patients with and without cALNM (log-rank p = 0.000). A multivariate Cox regression analysis revealed that cALNM and thoracic surgery (mediastinal lymphadenectomy via conventional open right thoracotomy or video-assisted thoracoscopic surgery) independently predicted CSS (p = 0.0007 and 0.021, respectively). Moreover, a significant difference in systemic recurrence-free survival was observed between those with and without cALNM (log-rank p = 0.000). Multivariate Cox regression analysis revealed that cALNM and sex independently predicted systemic recurrence-free survival (p = 0.000 and 0.015, respectively). Conclusion cALNM was an independent poor prognostic factor for CSS after EC surgery. It may also be an independent prognostic factor for postoperative systemic recurrence, which can shorten the CSS. For patients with cALNM-positive EC who have a high potential risk of systemic metastases, more extensive treatment besides the conventional perioperative systemic chemotherapy may be necessary.

scholarly journals Clinical Impact of Abdominal Versus Mediastinal Metastases as a Prognostic Factor for Poor Outcomes Following Esophageal Cancer Surgery: A Retrospective Study

2020 ◽  
Author(s):  
Yutaka Miyawaki ◽  
Hiroshi Sato ◽  
Shuichiro Oya ◽  
Hirofumi Sugita ◽  
Yasumitsu Hirano ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Lymph Node ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Systemic Recurrence ◽  
Significant Difference ◽  
Node Metastases

Abstract BackgroundSurgery is still the mainstay of radical treatment for resectable esophageal cancer (EC). It is apparent that the presence or spread of lymph node metastasis is a powerful prognostic factor in patients with EC who are eligible for curative treatment. Although the importance and efficacy of lymph node dissection in radical esophagectomy have been reported, the clinical or prognostic relevance of specific metastatic patterns within the mediastinal cavity and abdomen remains unclear. MethodsWe retrospectively analyzed the association between postoperative survival with clinical mediastinal lymph node metastases (cMLNMs) and abdominal lymph node metastases (cALNMs) in 143 patients who underwent radical EC surgery at our hospital between May 2012 and July 2017.ResultsA significant difference in cause-specific survival (CSS) was observed between patients with and without cALNM (log-rank p=0.000). A multivariate Cox regression analysis revealed that cALNM and thoracic surgery (mediastinal lymphadenectomy via conventional open right thoracotomy or video-assisted thoracoscopic surgery) independently predicted CSS (p=0.001 and 0.037, respectively). Moreover, a significant difference in systemic recurrence-free survival was observed between those with and without cALNM (log-rank p=0.000). Multivariate Cox regression analysis revealed that cALNM and sex independently predicted systemic recurrence-free survival (p=0.005 and 0.013, respectively). ConclusioncALNM was an independent poor prognostic factor for CSS after EC surgery. It may also be an independent prognostic factor for postoperative systemic recurrence, which can shorten CSS. For patients with cALNM-positive EC who have a high potential risk of systemic metastases, more extensive treatment besides the conventional perioperative systemic chemotherapy may be necessary.

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

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.

National trends in local excision and esophagectomy for cT1N0 esophageal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 62-62 ◽  
Author(s):  
Emily C. Sturm ◽  
Whitney Zahnd ◽  
John D. Mellinger ◽  
Sabha Ganai
Keyword(s):  
Esophageal Cancer ◽  
Regression Analysis ◽  
Local Excision ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Chi Square ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Chi Square Analysis ◽  
Over Time

62 Background: Esophageal cancer management has evolved due to improvements in staging and treatment strategies. Endoscopic local excision presents an attractive option for definitive management of T1 cancers, avoiding the morbidity of esophagectomy. We hypothesized that for cT1N0 cancers, patients who underwent local excision would have lower survival compared to esophagectomy due to potential discordant staging. Methods: The National Cancer Database was queried for esophageal squamous cell carcinoma (SCC) and adenocarcinoma (AC) with AJCC T1N0 clinical stage who underwent local excision (n = 1625) or esophagectomy (n = 3255) between 1998 and 2012. Chi-square analysis was used to compare demographic and clinical characteristics by procedure. Chi-square trend analysis was performed to assess trends in procedure type over time. Cox Regression analysis was performed to assess survival by procedure controlling for demographic and clinical characteristics. Results: Between 1998 and 2012, the proportion of patients who underwent local excision increased from 12% to 50% for all patients (p < 0.001); from 17% to 40% for SCC patients (p < 0.001); and from 9% to 51% for AC patients (p < 0.001). Surgical procedure varied significantly by demographic, socioeconomic status, facility, and tumor-related factors. 65% of cT1N0 cancers had concordant clinical and pathological staging after esophagectomy, with 11% having positive nodal disease; 44% were concordant after local excision. While no significant difference was seen in unadjusted survival, adjusted Cox Regression analysis indicated worse survival after esophagectomy compared to local excision for all cases (HR 1.67; 95% CI, 1.40-2.00) and for ACs with concordant staging (HR 1.54; 95% CI, 1.11-2.14). Conclusions: Local excision for cT1N0 esophageal cancer has increased over time. Staging concordance for esophagectomy is seen in two-thirds of cases. Contrary to our hypothesis, patients undergoing local excision for T1N0 cancers have better overall survival than those undergoing esophagectomy, which may reflect early differences in mortality and/or selection bias. As this study was unable to distinguish T1a from T1b, further analysis is warranted.

Prognostic impact of LDH and HCG levels in marker-positive seminomas.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 392-392 ◽  
Author(s):  
Christoph Alexander Seidel ◽  
Gedske Daugaard ◽  
Tim Nestler ◽  
Alexey Tryakin ◽  
Christian Daniel Fankhauser ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Serum Levels ◽  
Rank Test ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Oncological Outcomes ◽  
Log Rank Test

392 Background: The prognostic impact of LDH and HCG serum levels in marker positive metastatic seminoma patients is uncertain. This analysis evaluated the association between LDH and HCG levels with oncological outcomes in this patient population. Methods: Seminoma patients with elevated HCG levels were retrospectively analyzed. After stratification according to tumor marker levels pre- and post-orchiectomy, outcomes of subgroups were compared using log-rank test and cox-regression analysis. Study endpoints were cancer specific- (CSS) and recurrence-free survival (RFS). Results: In total, 429 HCG-positive metastatic seminoma patients (stage II n=291; stage III n=138) diagnosed between 1981 and 2018 were included. LDH + HCG levels ranged from 124 U/l to 8833 U/l (median: 619; IQR: 955) + 2 IU/l to 283,782 IU/l (median: 20; IQR: 63) pre- and from 107 U/l to 8650 U/l (median: 324; IQR: 481) + 0 IU/l to 36700 IU/l post-orchiectomy (median: 30; IQR: 121), respectively. Five-year CSS and RFS rates were 90% and 79%, respectively. Patients with LDH levels pre-orchiectomy <1.5 UNL (n=142) had a 5-year CSS (RFS) rate of 97% (88%), compared to 86% (81%) for ≥1.5 to 3 UNL (n=40), 83% (77%) for >3 to 5 UNL (n=44) and 83% (72%) for >5 UNL (n=44) (CSS p <0.001; RFS p=0.142). Concerning LDH levels post-orchiectomy this stratification was not significant but patients with LDH levels ≥3 UNL (n=77) displayed an impaired prognosis associated with a 5-year CSS (RFS) rate of 85% (79%) compared to 94% (82%) for levels <3 UNL (n=186) (CSS p=0.025; RFS p=0.447). Patients with HCG levels ≥2000 IU/l (n=17) pre- but not post-orchiectomy had a 5-year CSS (RFS) rate of 73% (60%) compared to 94% (79%) for patients with HCG levels <2000 IU/l (n=855) (CSS p=0.09; RFS p=0.04). In cox-regression analysis LDH ≥1.5 UNL (p=0.037; HR 3.32, CI95%1.08-10.26) and HCG levels ≥2000 IU/l (p=0.044; HR 3.69, 95%CI1.04-13.13) pre-orchiectomy were confirmed as prognostic factors for CSS. Conclusions: LDH levels inversely correlate with survival outcomes, suggesting ≥1.5 UNL pre- and ≥3 UNL post-orchiectomy as potential cut-off values for further risk assessment. Patients with extensive HCG elevations may represent an unfavorable subgroup concerning RFS and CSS, but only few patients were affected.

scholarly journals SCUBE3 serves as an independent poor prognostic factor in breast cancer

2021 ◽  
Author(s):  
Qin Huo ◽  
Xi He ◽  
Zhenwei Li ◽  
Fan Yang ◽  
Shengnan He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Functional Enrichment ◽  
High Expression ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Significant Difference

Abstract Background: Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. Methods: The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein-protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. Results: We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in age, histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2+ (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95 % CI: 1.20-6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95 % CI: 1.06-3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression.Conclusions: These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.

scholarly journals Significant Effect of Polymorphisms inCYP2D6andABCC2on Clinical Outcomes of Adjuvant Tamoxifen Therapy for Breast Cancer Patients

2010 ◽  
Vol 28 (8) ◽  
pp. 1287-1293 ◽  
Author(s):  
Kazuma Kiyotani ◽  
Taisei Mushiroda ◽  
Chiyo K. Imamura ◽  
Naoya Hosono ◽  
Tatsuhiko Tsunoda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Plasma Concentrations ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Tag Snps ◽  
Risk Alleles ◽  
Significant Difference ◽  
Variant Alleles

PurposeThe clinical efficacy of tamoxifen is suspected to be influenced by the activity of drug-metabolizing enzymes and transporters involved in the formation, metabolism, and elimination of its active forms. We investigated relationships of polymorphisms in transporter genes and CYP2D6 to clinical outcome of patients receiving tamoxifen.Patients and MethodsWe studied 282 patients with hormone receptor–positive, invasive breast cancer receiving tamoxifen monotherapy, including 67 patients who have been previously reported. We investigated the effects of allelic variants of CYP2D6 and haplotype-tagging single nucleotide polymorphisms (tag-SNPs) of ABCB1, ABCC2, and ABCG2 on recurrence-free survival using the Kaplan-Meier method and Cox regression analysis. Plasma concentrations of tamoxifen metabolites were measured in 98 patients receiving tamoxifen 20 mg/d.ResultsCYP2D6 variants were significantly associated with shorter recurrence-free survival (P = .000036; hazard ratio [HR] = 9.52; 95% CI, 2.79 to 32.45 in patients with two variant alleles v patients without variant alleles). Among 51 tag-SNPs in transporter genes, a significant association was found at rs3740065 in ABCC2 (P = .00017; HR = 10.64; 95% CI, 1.44 to 78.88 in patients with AA v GG genotypes). The number of risk alleles of CYP2D6 and ABCC2 showed cumulative effects on recurrence-free survival (P = .000000055). Patients carrying four risk alleles had 45.25-fold higher risk compared with patients with ≤ one risk allele. CYP2D6 variants were associated with lower plasma levels of endoxifen and 4-hydroxytamoxifen (P = .0000043 and .00052), whereas no significant difference was found among ABCC2 genotype groups.ConclusionOur results suggest that polymorphisms in CYP2D6 and ABCC2 are important predictors for the prognosis of patients with breast cancer treated with tamoxifen.

scholarly journals Sonographic Features of Triple-Negative Breast Carcinomas Are Correlated With mRNA–lncRNA Signatures and Risk of Tumor Recurrence

2021 ◽  
Vol 10 ◽  
Author(s):  
Jia-wei Li ◽  
Jin Zhou ◽  
Zhao-ting Shi ◽  
Na Li ◽  
Shi-chong Zhou ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Breast Imaging ◽  
Tumor Recurrence ◽  
Triple Negative ◽  
Cox Regression ◽  
Multivariate Logistic Regression Analysis ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Risk Of Recurrence

BackgroundTo determine a correlation between mRNA and lncRNA signatures, sonographic features, and risk of recurrence in triple-negative breast cancers (TNBC).MethodsWe retrospectively reviewed the data from 114 TNBC patients having undergone transcriptome analysis. The risk of tumor recurrence was determined based on the correlation between transcriptome profiles and recurrence-free survival. Ultrasound (US) features were described according to the Breast Imaging Reporting and Data System. Multivariate logistic regression analysis determined the correlation between US features and risk of recurrence. The predictive value of sonographic features in determining tumor recurrence was analyzed using receiver operating characteristic curves.ResultsThree mRNAs (CHRDL1, FCGR1A, and RSAD2) and two lncRNAs (HIF1A-AS2 and AK124454) were correlated with recurrence-free survival in patients with TNBC. Among the three mRNAs, two were upregulated (FCGR1A and RSAD2) and one was downregulated (CHRDL1) in TNBCs. LncRNAs HIF1A-AS2 and AK124454 were upregulated in TNBCs. Based on these signatures, an integrated mRNA–lncRNA model was established using Cox regression analysis to determine the risk of tumor recurrence. Benign-like sonographic features, such as regular shape, circumscribed margin, posterior acoustic enhancement, and no calcifications, were associated with HIF1A-AS2 expression and high risk of tumor recurrence (P&lt;0.05). Malignant-like features, such as irregular shape, uncircumscribed margin, no posterior acoustic enhancement, and calcifications, were correlated with CHRDL1 expression and low risk of tumor recurrence (P&lt;0.05).ConclusionsSonographic features and mRNA–lncRNA signatures in TNBCs represent the risk of tumor recurrence. Taken together, US may be a promising technique in determining the prognosis of patients with TNBC.

scholarly journals SCUBE3 serves as an independent poor prognostic factor in breast cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qin Huo ◽  
Xi He ◽  
Zhenwei Li ◽  
Fan Yang ◽  
Shengnan He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Functional Enrichment ◽  
High Expression ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Significant Difference

Abstract Background Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. Methods The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein–protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. Results We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2 + (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI 1.20–6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI 1.06–3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression. Conclusions These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.

scholarly journals A Novel Gene Signature-Based Model Predicts Biochemical Recurrence-Free Survival in Prostate Cancer Patients after Radical Prostatectomy

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 1 ◽  
Author(s):  
Shi ◽  
Bao ◽  
Weischenfeldt ◽  
Schaefer ◽  
Rogowski ◽  
...  
Keyword(s):  
Decision Making ◽  
Regression Analysis ◽  
Risk Factor ◽  
Biochemical Recurrence ◽  
Cox Regression ◽  
Gene Signature ◽  
Clinicopathological Features ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis

Abstract: Currently, decision-making regarding biochemical recurrence (BCR) following prostatectomy relies solely on clinical parameters. We therefore attempted to develop an integrated prediction model based on a molecular signature and clinicopathological features, in order to forecast the risk for BCR and guide clinical decision-making for postoperative therapy. Using high-throughput screening and least absolute shrinkage and selection operator (LASSO) in the training set, a novel gene signature for biochemical recurrence-free survival (BCRFS) was established. Validation of the prognostic value was performed in five other independent datasets, including our patient cohort. Multivariate Cox regression analysis was performed to evaluate the importance of risk for BCR. Time-dependent receiver operating characteristic (tROC) was used to evaluate the predictive power. In combination with relevant clinicopathological features, a decision tree was built to improve the risk stratification. The gene signature exhibited a strong capacity for identifying high-risk BCR patients, and multivariate Cox regression analysis demonstrated that the gene signature consistently acted as a risk factor for BCR. The decision tree was successfully able to identify the high-risk subgroup. Overall, the gene signature established in the present study is a powerful predictor and risk factor for BCR after radical prostatectomy.

scholarly journals Increased Expression of Integrin Subunit α3 is Correlated with Worse Recurrence-Free Survival in Thyroid Cancer

2021 ◽  
Author(s):  
Jun-jie Ma ◽  
Cheng Xiang ◽  
Heng-qing Zhu ◽  
Bing-long Bai ◽  
Ping Wang
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Genetic Alterations ◽  
Functional Enrichment ◽  
Integrin Subunit ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis

Abstract Objective: To investigate the potential effect of integrin subunit α3 (ITGA3) on thyroid cancer (THCA). Materials and Methods: Based on bioinformatics databases, the expression levels of ITGA3 were firstly analyzed, followed by evaluating the prognostic significance of ITGA3 in THCA patients. Cox regression analysis predicted the independent prognostic factors for THCA. Then, cBioportal and GSCA databases were applied to evaluate genetic alterations of ITGA3. Functional enrichment analysis was conducted using the R package. Finally, the upstream microRNAs of ITGA3 were determined. Results: ITGA3 gene and protein levels were higher in the THCA group than normal group (all P <0.05). And ITGA3 mRNA expression was significantly related to cancer stage and histological subtype (all P <0.01). Moreover, high expression of ITGA3 was associated with poor recurrence-free survival (RFS) of THCA patients in all subgroups (all P <0.01). Cox regression analysis presented that ITGA3 overexpression was an independent prognostic factor for worse RFS in THCA patients. Besides, significant relations were observed between ITGA3 and genetic alterations (FDR <0.01). Functional enrichment analysis indicated ECM-receptor interaction, and cell adhesion molecules were the shared regulatory pathways. We also found that ITGA3 might be the target gene of hsa-miR-3129, hsa-miR-181d, hsa-miR-181b, hsa-miR-199a, and hsa-miR-199b, which were all correlated with THCA patient prognosis. Conclusions: ITGA3 could be a reliable biomarker and promising therapeutic target for improving the diagnosis and clinical outcomes of THCA patients.

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