Prognostic risk stratification value of MACC1 expression in patients with gastric cancer.

BACKGROUND: The prognostic significance of metastasis-associated in colon cancer-1 (MACC1) has been explored in a variety of malignancies. However, its clinical relevance in patients with gastric cancer (GC) is limited, also remains controversial. METHOD: In this study, we retrospectively evaluated the prognostic value of lesion MACC1 expression in 347 GC patients. Lesion MACC1 expression was analyzed with immunohistochemistry and grouped as MACC1low (n = 172) and MACC1high (n = 175) cases. RESULTS: Data revealed that the degree of MACC1 expression is not related to patient sex, age and disease stage (all p > 0.05). Survival analysis showed that only post-operation advanced pT (p = 0.018), pN (p < 0.001), pM (p = 0.001) and AJCC stages (p < 0.001) are significantly associated with shorter survival, while no obvious difference was observed between MACC1low and MACC1high cases (p = 0.158). However, we found that survival for female (p = 0.032), older (p = 0.028), and early disease stage (pT stage I + II, p = 0.033) patients with MACC1high are remarkably worse than those with MACC1low. CONCLUSION: In summary, our findings revealed that, though MACC1 expression is not associated with the survival of the whole cohort, the prognostic risk stratification value of lesion MACC1 expression in subgroups of patients with gastric cancer should be noted.

Pre-operative neutrophil-to-lymphocyte ratio is an independent prognostic factor in patients with gastric cancer.

OBJECTIVE: To evaluate the prognostic significance of peripheral lymphocyte count and its derived inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), in a cohort of patients with gastric cancer (GC). METHODS: In this retrospective study, the clinical characteristics and follow-up information, both pre- and post-operative within one week of laboratory findings, of 338 patients with GC who underwent radical gastrectomy were retrieved, and their prognostic significance was evaluated. RESULTS: Both lower pre- and post-operative lymphocyte counts and higher NLR and SSI were significantly related to advanced tumour (pT) and disease stages (American Joint Committee on Cancer [AJCC]) in patients with GC. Log-rank survival analysis showed that, in addition to traditional pT, pN, pM, and AJCC stages, both lower pre- (p = 0.041) and post-operative (p = 0.002) lymphocyte counts and higher NLR (ppre < 0.001 and ppost = 0.008) and SSI (ppre = 0.014 and ppost = 0.145) were associated with worse survival. Cox proportional hazards analysis revealed that pre-operative NLR (p = 0.018; hazard ratio = 1.778) was an independent predictor of prognosis in patients with GC. Moreover, when the pre-operative NLR was divided into NLRlow and NLRhigh, NLRhigh showed stratified prognostic value for patient sex (male, p = 0.001; female, p = 0.044), age (younger, p = 0.005; older, p = 0.005), and AJCC stage III (p = 0.007). CONCLUSION: Pre-operative NLR is an independent prognostic factor for patients with GC and has stratified prognostic value for patients with AJCC stage III GC.

Prognostic significance of the immune checkpoint HLA-G/ILT-4 in the survival of patients with gastric cancer.

OBJECTIVE: Human leukocyte antigen-G (HLA-G) and its receptors, including immunoglobulin-like transcripts (ILT)-2 and ILT-4, are closely associated with cancer development and clinical outcomes of patients. However, the clinical significance of HLA-G and ILT-2/-4 in gastric cancer (GC) is limited. METHODS: In this study, the percentage of HLA-G-, ILT-2 and ILT-4 positive tumor cells in 127 GC lesion suspensions of tumor cells gated for epithelialcelladhesionmolecule(EpCAM) was determined using multicolor flow cytometry and their clinical significance was evaluated. RESULTS: Our data showed that the median percentages of HLA-G-, ILT-2, and ILT-4 expressing GC cells were 18.0%, 67.80%, and 1.42%, respectively, and co-expression of HLA-G/ILT-2, HLA-G/ILT-4, and ILT-2/ILT-4 was 16.9%, 1.42%, and 1.70%, respectively. Kaplan-Meier survival results revealed that besides post-operation N status (p = 0.006), M status (p = 0.001), and AJCC clinical stage (p < 0.001), only high percentage of ILT-4+ GC cells was a significant factor for worse survival of patients with GC (overall survival [OS]: 42.9 months vs. 84.5 months; p = 0.031). However, among female patients with GC (n = 31), high percentage of either HLA-G+ (OS: 18.5 months vs. 89.3 months; p = 0.001) or ILT-4+ (OS: 17.9 months vs. 85.8 months; p = 0.002) GC cells was markedly associated with a poor prognosis. CONCLUSION: Our findings revealed that among HLA-G, ILT-2, and ILT-4, only a high percentage of ILT-4+ GC cells was significantly related to poor prognosis in the entire cohort of patients with GC. However, high percentage of HLA-G+ and ILT-4+ GC cells is associated with poor clinical outcome among female patients with GC.

Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer.

BACKGROUND: Bladder cancer is the 10th most common cancer and most common urothelial malignancy worldwide. Prognostic biomarkers for bladder cancer patients are required for individualized treatment. Monocarboxylate transporter 4 (MCT4), encoded by SLC16A3 gene, is a potential biomarker for bladder cancer because of its crucial role in the lactate efflux in the aerobic glycolysis process. We aimed to study the association between MCT4 expression and the overall survival (OS) of bladder cancer patients. METHODS: The published single-cell RNA sequencing data of 49,869 bladder cancer cells and 15,827 normal bladder mucosa cells and The Cancer Genome Atlas (TCGA) bladder cancer cohort data were used to explore the mRNA expression of SLC16A3 in bladder cancer. Eighty-nine consecutive bladder cancer patients who had undergone radical cystectomy were enrolled as a validation cohort. The expression of MCT4 proteins in bladder cancer specimens was detected using immunohistochemistry staining. The Kaplan-Meier survival analysis and Cox regression were performed to analyze the association between MCT4 protein expression and OS in bladder cancer patients. RESULTS: SLC16A3 mRNA was upregulated in bladder cancer cells. The upregulated genes in SLC16A3-positive epithelial cells were enriched in the glycolysis process pathway and monocarboxylic acid metabolic process pathway. Patients with high SLC16A3 mRNA expression showed significantly poor OS (p = 0.016). High MCT4 protein expression was also found to be an independent predictor for poor OS in bladder cancer patients (HR: 2.462; 95% CI: 1.202~5.042, p = 0.014). A nomogram was built based on the results of the multivariate Cox analysis. CONCLUSION: Bladder cancer with high SLC16A3 mRNA expression has a poor OS. High MCT4 protein expression is an independent prognostic factor for bladder cancer patients who had undergone radical cystectomy.

Comprehensive Transcriptomic Analysis Reveals the Role of the Immune Checkpoint HLA-G Molecule in Cancers.

Human leukocyte antigen G (HLA-G) is known as a novel immune checkpoint molecule in cancer; thus, HLA-G and its receptors might be targets for immune checkpoint blockade in cancer immunotherapy. The aim of this study was to systematically identify the roles of checkpoint HLA-G molecules across various types of cancer. ONCOMINE, GEPIA, CCLE, TRRUST, HAP, PrognoScan, Kaplan-Meier Plotter, cBioPortal, LinkedOmics, STRING, GeneMANIA, DAVID, TIMER, and CIBERSORT were utilized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. In this study, we comprehensively analysed the heterogeneous expression of HLA-G molecules in various types of cancer and focused on genetic alterations, coexpression patterns, gene interaction networks, HLA-G interactors, and the relationships between HLA-G and pathological stage, prognosis, and tumor-infiltrating immune cells. We first identified that the mRNA expression levels of HLA-G were significantly upregulated in both most tumor tissues and tumor cell lines on the basis of in-depth analysis of RNAseq data. The expression levels of HLA-G were positively associated with those of the other immune checkpoints PD-1 and CTLA-4. Abnormal expression of HLA-G was significantly correlated with the pathological stage of some but not all tumor types. There was a significant difference between the high and low HLA-G expression groups in terms of overall survival (OS) or disease-free survival (DFS). The results showed that HLA-G highly expressed have positive associations with tumor-infiltrating immune cells in the microenvironment in most types of tumors (P<0.05). Additionally, we identified the key transcription factor (TF) targets in the regulation of HLA-G expression, including HIVEP2, MYCN, CIITA, MYC, and IRF1. Multiple mutations (missense, truncating, etc.) and the methylation status of the HLA-G gene may explain the differential expression of HLA-G across different tumors. Functional enrichment analysis showed that HLA-G was primarily related to T cell activation, T cell regulation, and lymphocyte-mediated immunity. The data may provide novel insights for blockade of the HLA-G/ILT axis, which holds potential for the development of more effective antitumour treatments.

HLA-G/ILTs Targeted Solid Cancer Immunotherapy: Opportunities and Challenges.

Immune checkpoint inhibitors (ICIs) have become a promising immunotherapy for cancers. Human leukocyte antigen-G (HLA-G), a neoantigen, its biological functions and clinical relevance have been extensively investigated in malignancies, and early clinical trials with "anti-HLA-G strategy" are being launched for advance solid cancer immunotherapy. The mechanism of HLA-G as a new ICI is that HLA-G can bind immune cell bearing inhibitory receptors, the immunoglobulin-like transcript (ILT)-2 and ILT-4. HLA-G/ILT-2/-4 (HLA-G/ILTs) signaling can drive comprehensive immune suppression, promote tumor growth and disease progression. Though clinical benefits could be expected with application of HLA-G antibodies to blockade the HLA-G/ILTs signaling in solid cancer immunotherapy, major challenges with the diversity of HLA-G isoforms, HLA-G/ILTs binding specificity, intra- and inter-tumor heterogeneity of HLA-G, lack of isoform-specific antibodies and validated assay protocols, which could dramatically affect the clinical efficacy. Clinical benefits of HLA-G-targeted solid cancer immunotherapy may be fluctuated or even premature unless major challenges are addressed.

Prognostic Significance of Immune Checkpoints HLA-G/ILT-2/4 and PD-L1 in Colorectal Cancer.

Immune checkpoint inhibitors (ICIs) have become a promising area of research for cancer treatment. In addition to the well-known ICIs targeting PD-1/PD-L1, HLA-G/ILT-2/-4 is relatively new immune checkpoint that has been evaluated in early clinical trials in patients with advanced solid tumors. In this study, the expression of HLA-G (n=157), ILT-2/4 (n=82), and PD-L1 (n=70) in epithelial cell adhesion molecule (EpCAM)-positive colorectal cancer (CRC) cells was analyzed by multicolor flow cytometry, and the prognostic significance of these molecules was evaluated. In EpCAM+ CRC cells, the median percentages of HLA-G, ILT-2, ILT-4, and PD-L1 were 14.90%, 67.70%, 8.55% and 80.30%, respectively. In addition, a positive correlation was observed between them (all p<0.001). Higher levels of these immune checkpoint proteins are associated with lymph node metastasis. In addition to the AJCC stage (p=0.001), Kaplan-Meier survival analysis showed that higher levels of HLA-G (p=0.041), ILT-2 (p=0.060), ILT-4 (p<0.001), PD-L1 (p=0.012), HLA-GILT4 (p<0.001) and ILT-2ILT-4 (p<0.001) were significantly associated with shorter survival of CRC patients. When CRC patients were stratified by early and advanced AJCC stages, HLA-G levels were only related to the survival among CRC patients with early disease stage (p=0.024), while ILT-4 levels were significant for both CRC patients with early (p=0.001) and advanced (p=0.020) disease stages. Multivariate cox regression analysis revealed that advanced AJCC stage (HR=2.435; p=0.005) and higher ILT-4 levels (HR=2.198; p=0.063) were independent risk factors for poor outcomes in patients with CRC. In summary, among the immune checkpoints, HLA-G/ILT-2/4 and PD-L1, ILT-4 is the most significant prognostic indicator of CRC. This finding indicated that a combination of immunotherapy strategies, such as ILT-4 blockade, could improve the clinical outcomes in patients with cancer. Moreover, multicolor flow cytometry can be employed as a reliable and efficient, alternative to immunohistochemistry, for evaluating the immune checkpoint proteins expressed in tumor lesions.

Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions.

Signaling pathway between human leukocyte antigen (HLA)-G and immune inhibitory receptors immunoglobulin-like transcript (ILT)-2/4 has been acknowledged as one of immune checkpoints, and as a potential target for cancer immunotherapy. Like other immune checkpoints, inter- and even intratumor heterogeneity of HLA-G could render a rather complexity for HLA-G-target immunotherapy. However, little information for intratumor heterogeneity of HLA-G is available. In this study, HLA-G expression in a serial section of colorectal cancer (CRC) lesions from three CRC patients (each sample with serial section of 50 slides, 10 randomized slides for each antibody), three different locations within a same sample (five CRC), and three case-matched blocks that each includes 36 esophageal cancer samples, were evaluated with immunohistochemistry using anti-HLA-G antibodies (mAbs 4H84, MEM-G/1 and MEM-G/2 probing for all denatured HLA-G isoforms, 5A6G7, and 2A12 probing for denatured HLA-G5 and HLA-G6 isoforms). Our results revealed that, in addition to the frequently observed inter-tumor heterogeneity, intratumor heterogeneous expression of HLA-G is common in different areas within a tumor in CRC and esophageal cancer samples included in this study. Moreover, percentage of HLA-G expression probed with different anti-HLA-G antibodies also varies dramatically within a tumor. Given HLA-G has been considered as an important immune checkpoint, intratumor heterogeneity of HLA-G expression, and different specificity of anti-HLA-G antibodies being used among studies, interpretation and clinical significance of HLA-G expression in cancers should be with caution.

The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis.

Human leukocyte antigen (HLA)-G, a non-classical HLA-class I molecule, has a low polymorphism frequency, restricted tissue distribution and immunoinhibitory property. HLA-G expression in tumor cells and cells chronically infected with virus may enable them to escape from host immune surveillance. It is well-known that the HLA-G molecule is a novel biomarker and potential therapeutic target that is relevant in various types of cancers, but its role in cervical cancer has not been fully explored. In this review, we aim to summarize and discuss the immunologic role of the HLA-G molecule in the context of HPV infections and the process of cervical cancer carcinogenesis. A better understanding of the potential impact of HLA-G on the clinical course of persistent HPV infections, cervical epithelial cell transformation, tumor growth, recurrence and metastasis is needed to identify a novel diagnostic/prognostic biomarker for cervical cancer, which is critical for cervical cancer risk screening. In addition, it is also necessary to identify HLA-G-driven immune mechanisms involved in the interactions between host and virus to explore novel immunotherapy strategies that target HLA-G/immunoglobulin-like transcript (ILT) immune checkpoints.

Higher Levels of Pre-operative Peripheral Lymphocyte Count Is a Favorable Prognostic Factor for Patients With Stage I and II Rectal Cancer.

The clinical significance of peripheral blood parameters has been considered to be a potential prognostic indicator for malignancies. In this study, 224 colorectal cancer (CRC; ncolon = 103; nrectal = 121) patients who underwent resection were enrolled, and the pre- and post-operative clinical laboratory data within 1 week, before and after surgery, were collected. The prognostic value of the counts of white blood cell (WBC), neutrophil, lymphocyte and platelet, the neutrophil to lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) were analyzed. Data revealed that pre-operative lymphocyte count (pre-LC) was much higher than that of post-LC (p < 0.001), and only rectal cancer patients with pre-LChigh (>median: 1.61 × 109/L) had a significantly better overall survival (OS) and 5-year survival rate (SR) than those with pre-LClow (OS: 62.3 vs. 49.5 months; SR: 74.0 vs. 43.0%; p = 0.006). Cox's proportional hazard models revealed that pre-LChigh was an independent, favorable prognostic factor for rectal cancer patients (hazard ratio = 0.348; p = 0.003). Moreover, when the disease stages were stratified, the pre-LChigh was significantly associated with better prognosis of rectal cancer patients with stage I + II rectal cancer (n = 65; OS: 67.5 vs. 54.3 months; p = 0.011). Taken together, our study revealed that pre-operative lymphocyte count is an independent prognostic factor for patients with stage I and II rectal cancer.

Intercellular transfer of HLA-G: its potential in cancer immunology.

Intercellular protein transfer between cancer cells and immune cells is a very common phenomenon that can affect different stages of host antitumor immune responses. HLA-G, a non-classical HLA class I antigen, has been observed to be widely expressed in various malignancies, and its immune-suppressive functions have been well recognised. HLA-G expression in cancer cells can directly mediate immune tolerance by interacting with inhibitory receptors such as ILT2 and ILT4 expressed on immune cells. Moreover, a network of multiple directional intercellular transfers of HLA-G among cancer cells and immune cells through trogocytosis, exosomes and tunnelling nanotubes provides malignant cells with an alternative ploy for antigen sharing and induces more complex heterogeneity, to modulate immune responses, ultimately leading to immune evasion, therapy resistance, disease progression and poor clinical outcome. Herein, we discuss the relative aspects of the intercellular transfer of HLA-G between tumor cells and immune cells and its potential use in tumor immunology research and translational cancer therapy.

Predictive value of post-operative neutrophil/lymphocyte count ratio for surgical site infection in patients following posterior lumbar spinal surgery.

OBJECTIVE: Surgical site infection (SSI) is a common complication in patients following posterior lumbar spinal surgery. Various laboratory data such as laboratory parameters derived neutrophil/lymphocyte count ratio (NLR), have been applied for the prediction of SSI, but more studies are necessary to evaluate the significance of these indicators. Here, our study aims to investigate the predictive value of total white blood cells (WBCs), count and percentages of neutrophils and leukocytes, NLR, and C-reactive protein (CRP) for surgical site infection (SSI) in patients after posterior lumbar spinal surgery. METHODS: A total of 293 patients who underwent posterior lumbar spinal surgery were enrolled in this study. Each patient's medical history was retrospectively reviewed, and patients were divided into the deep SSI group (n = 13) and the non-SSI group (n = 280). Laboratory data including total WBC, count and percentages of neutrophils and leukocytes, NLR at 1 week before the operation and the 4 and 7 days post-operation, and CRP at 4 and 7 days post-operation were analysed between the SSI and non-SSI groups. Moreover, predictive power and cut-off of NLR for SSI were determined by receiver operating characteristic curve (ROC) results. RESULTS: Data revealed that the medians of NLR were markedly increased in the SSI group as compared to that in non-SSI group at 4 days (p = 0.011) and 7 days (p = 0.047) post-operation. Moreover, the neutrophil percentage was also dramatically increased in the SSI group at both 4 and 7 days post-operation (p = 0.010 and p = 0.030) respectively compared to the non-SSI group. However, no significant difference was observed between the groups 1 week before the operation. ROC results showed that NLR at 4 days (cut-off >5.19; sensitivity: 61.5%; specificity: 77.6%; AUC = 0.708) and 7 days (cut-off >3.85; sensitivity: 69.2%; specificity: 62.7%; AUC = 0.663) post-operation could significantly discriminate the SSI and non-SSI groups. Logistic regression analysis showed that NLR at both post-operative time points (OR = 1.218; p = 0.003 and OR = 1.296; p = 0.048) could be valuable predictors for SSI. CONCLUSION: NLR at 4 and 7 days post-operation are valuable laboratory predictors for SSI in patients with posterior lumbar spinal surgery.

The Emerging Roles of Human Leukocyte Antigen-F in Immune Modulation and Viral Infection.

Human leukocyte antigens (HLAs) play various critical roles in both innate and adaptive immunity through processes such as presenting antigens to T cells and serving as ligands for receptors expressed on natural killer (NK) cells. Among the HLA class I family, the clinical significance and biological function of HLA-F have been the least investigated and have remained elusive for a long period of time. Previous studies have revealed that HLA-F expression might be involved in various physiological and pathological processes, such as pregnancy, viral infection, cancer, transplantation, and autoimmune diseases. However, recent data have shown that, akin to other HLA family members, HLA-F molecules can interact with both activating and inhibitory receptors on immune cells, such as NK cells, and can present a diverse panel of peptides. These important findings pave new avenues for investigations regarding the functions of HLA-F as an important immune regulatory molecule. In the present review, we summarize the studies on the role of HLA-F in immune modulation, with a special emphasis placed on the roles of HLA-F and KIR3DS1 interactions in viral infection.

Prognostic and Risk Stratification Value of Lesion MACC1 Expression in Colorectal Cancer Patients.

The up-regulated metastasis-associated in colon cancer 1 (MACC1) expression and its clinical significance has been explored in a varity of malignancies. In this study, lesion MACC1 expression in 503 CRC patients (N colon = 332, N rectal = 171) were analyzed with immunohistochemistry, and its correlation with clinical parameters, patient survival, and its impact on prognostic stratification were evaluated. Data revealed the survival of patient with MACC1high is markedly worse than that of MACC1low (mean overall survival: 80.1 vs. 90.4 months; p = 0.001) and is an independent prognostic predictor (hazard ratio = 1.533; p = 0.005). More importantly, for the first time, we demonstrated that MACC1 status exhibited a significantly prognostic power for stratified clinical parameters such as patient age and gender, particular TNM status, and distinct AJCC disease stage. In summary, our findings indicated that MACC1 is a valuable prognostic and risk stratification biomarker for colorectal cancer patients.

Significance of plasma MACC1 levels on the prognostic stratification in patients with colorectal cancer.

The clinical significance of metastasis-associated in colon cancer-1 (MACC1) has been investigated but the relevance of peripheral MACC1 levels was rather limited. Herein, our data revealed that plasma MACC1 levels in 117 colorectal cancer patients (CRC) were dramatically higher than that in normal controls (P < 0.001), and with a strong discrimination power between the two groups (AUC = 0.960, P < 0.001). Moreover, MACC1 is an independent prognostic factor for CRC patients. When clinical parameters stratified by MACC1low and MACC1high , MACC1 levels exhibited further significant predictive value. Summary, plasma MACC1 levels could be a useful prognostic and diagnostic biomarker, and could improve the prognostic value of traditional prognosticators for colorectal cancer patients.

Heterogeneity of HLA-G Expression in Cancers: Facing the Challenges.

Phenotypic heterogeneity has been observed in most malignancies, which represents a considerable challenge for tumor therapy. In recent decades, the biological function and clinical significance of the human leukocyte antigen (HLA)-G have been intensively explored. It is now widely accepted that HLA-G is a critical marker of immunotolerance in cancer cell immune evasion and is strongly associated with disease progress and prognosis for cancer patients. Moreover, it has recently been emphasized that the signaling pathway linking HLA-G and immunoglobulin-like transcripts (ILTs) is considered an immune checkpoint. In addition, HLA-G itself can generate at least seven distinct isoforms, and intertumor and intratumor heterogeneity of HLA-G expression is common across different tumor types. Furthermore, HLA-G heterogeneity in cancers has been related to disease stage and outcomes, metastatic status and response to different therapies. This review focuses on the heterogeneity of HLA-G expression in malignant lesions, and clinical implications of this heterogeneity that might be relevant to personalized treatments are also discussed.

Clinical Significance of Potential Unidentified HLA-G Isoforms Without α1 Domain but Containing Intron 4 in Colorectal Cancer Patients.

The ectopic HLA-G expression in malignancies has been extensively explored and clinical significance of the molecule was widely acknowledged. Besides previously well-documented seven isoforms (HLA-G1~-G7), other novel isoforms of HLA-G have been reported but their clinical relavenace remians evaluated. In this study, lesion HLA-G expression in 379 case-matched serial section primary colorectal cancers (CRC) were evaluated with mAb 4H84 (recognizing an epitope in HLA-G α1 domain), and mAb 5A6G7 (recognizing an epitope encoded by intron 4), respectively. Data showed that HLA-G positive staining with mAbs 4H84 and 5A6G7 was 70.7 and 60.4%, respectively. When percentage of HLA-G expression detected with mAb 4H84 subtracted that with mAb 5A6G7, the difference (ΔHLA-G) with negative (ΔHLA-Gneg), comparable (ΔHLA-Gcom) and positive (ΔHLA-Gpos) were observed in 64 (16.9%), 159 (42.0%), and 156 (41.2%) cases, respectively. Noteworthy, unexpected immunostaining was observed in 44 (11.6%) lesions that no staining was detected with mAb 4H84 but positive with mAb 5A6G7 (4H84neg5A6G7pos). This staining pattern was unpredictable because all seven known HLA-G isoforms containing the α 1 domain could be recognized by the mAb 4H84. Moreover, patients with ΔHLA-Gneg had obviously better survival than those with ΔHLA-Gcom and ΔHLA-Gpos (p = 0.017), and ΔHLA-G could be an independent prognostic factor for CRC patients (p = 0.008). Our findings provides the first report that potential unidentified HLA-G isoforms is of distinct clinical significance in CRC patients.

Prevalence of human papillomavirus genotypes and relative risk of cervical cancer in China: a systematic review and meta-analysis.

High-risk HPV (hrHPV) is related to cervical carcinogenesis, although clinical data comparing the natural history and carcinogenic potential of type-specific HPV remain limited. Furthermore, the nationwide prevalence rates of overall and type-specific HPV among women with cervical precancerous lesions and cancer have not been reported. Here, a meta-analysis was performed for type-specific HPV distribution among 30,165 HPV-positive women, including 12,094 invasive cervical cancers (ICCs), 10,026 cervical intraepithelial neoplasia grade 2/3 (CIN2/3), 3246 CIN1, and 4799 normal cervices from 45 PCR-based studies. We found that HPV16 was the most common hrHPV type involved in cervical disease. The HPV16 positivity rate varied little across normal (22.7%) and CIN1 individuals (23.6%) but increased through the CIN2 (37.6%) and CIN3 patients (51.9%) to 65.6% in ICC cases. HPV16, 18, 35, 39, 45, and 59 were more frequent in ICC than CIN3, with ICC:CIN3 ratios ranging from 2.3 for HPV18 to 1.1 for HPV35/45. HPV31, 33, 52, and 58 were more frequent in CIN3 compared with normal cervices but less common in ICC compared with CIN3 (ICC:CIN3 ratios ranging from 0.6 for HPV58 and 0.4 for HPV52). The ICC:normal ratios were particularly high for HPV18, 52 and 58 in West China (4.1, 3.9 and 2.9, respectively) and for HPV45 and 59 in North China (1.6 and 1.1, respectively). In summary, this study is the most comprehensive analysis of type-specific HPV distribution in cervical carcinogenesis and could be valuable for HPV-based cervical cancer screening strategies and vaccination policies in China.