查看“PIK3CA”的源代码

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            <strong>PIK3CA</strong> 基因编码磷脂酰肌醇-3-激酶（PI3K）的 <strong>p110α</strong> 催化亚基。作为 <strong>[[PI3K/AKT/mTOR信号通路]]</strong> 的核心组分，PIK3CA 在调节细胞生长、增殖、存活、代谢及血管生成中发挥枢纽作用。在生理条件下，PI3K 的激活受到受体酪氨酸激酶（RTK）的精确调控。然而，当 PIK3CA 发生激活性突变（常见于激酶结构域 <strong>H1047R</strong> 或螺旋结构域 <strong>E542K/E545K</strong>）时，会导致 PI3K 信号持续性活化，进而驱动肿瘤的发生与进展，并诱导对内分泌治疗、靶向治疗的获得性耐药。它是人类实体瘤中突变频率最高的癌基因之一。
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            <div style="font-size: 1.25em; font-weight: bold; letter-spacing: 1.2px;">PIK3CA (p110α)</div>
            <div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Gene & Protein Profile (点击展开)</div>
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                    [[文件:Protein_PIK3CA_Structure_PDB.png|110px|p110α 催化亚基结构 (PDB: 4JPS)]]
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                <div style="font-size: 0.85em; color: #64748b; margin-top: 15px; font-weight: 600;">p110α/p85α 复合物</div>
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                    <th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc; width: 40%;">基因符号</th>
                    <td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;"><strong>PIK3CA</strong></td>
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                    <th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">基因全名</th>
                    <td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha</td>
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                    <th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">常用别名</th>
                    <td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">PI3K-alpha, p110α, CLOVE, MCM</td>
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                    <th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">染色体位置</th>
                    <td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">3q26.32</td>
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                    <th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">生物分类</th>
                    <td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;"><em>Homo sapiens</em> (智人)</td>
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                    <th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">Entrez Gene</th>
                    <td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">5290</td>
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                    <th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">HGNC ID</th>
                    <td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">8975</td>
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                    <th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">OMIM</th>
                    <td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">171834</td>
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                    <th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">UniProt</th>
                    <td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">P42336</td>
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                    <th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">酶学分类</th>
                    <td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">脂质激酶 (EC 2.7.1.153)</td>
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                    <th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">蛋白长度</th>
                    <td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">1068 AA</td>
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                    <th style="text-align: left; padding: 8px 15px; color: #475569; background-color: #f8fafc;">分子量</th>
                    <td style="padding: 8px 15px; color: #0f172a;">~110 kDa</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分子机制与致癌路径</h2>
    
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        PIK3CA 突变通过解除 p85 调节亚基的抑制作用或增强与膜脂质的结合能力，催化脂质第二信使 PIP3 的过量产生。这一过程启动了下游效应级联，最终导致蛋白质合成失控。
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            PIK3CA 突变<br><span style="font-size: 0.85em; opacity: 0.8; font-weight: normal;">(螺旋/激酶域)</span>
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        <div style="color: #94a3b8; font-size: 1.5em;">➔</div>
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            PIP3 积聚<br><span style="font-size: 0.85em; opacity: 0.8; font-weight: normal;">& AKT 磷酸化</span>
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        <div style="color: #94a3b8; font-size: 1.5em;">➔</div>
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            mTOR 激活<br><span style="font-size: 0.85em; opacity: 0.8; font-weight: normal;">& 蛋白合成增加</span>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">临床特征与治疗现状客观评估</h2>
    <p style="margin: 15px 0; text-align: justify;">
        基于目前精准肿瘤学证据，PIK3CA 在不同瘤种中的分布及靶向干预现状分析如下：
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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 22%;">评估维度</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">临床客观表现与技术特征</th>
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                <td style="padding: 12px; border: 1px solid #cbd5e1; font-weight: 600; background-color: #fcfdfe; color: #546e7a;">乳腺癌关联性</td>
                <td style="padding: 12px; border: 1px solid #cbd5e1; color: #334155; line-height: 1.6;">约 <strong>40%</strong> 的 HR+/HER2- 晚期乳腺癌携带 PIK3CA 突变。它是该亚型最主要的驱动因子之一，且与氟维司群等内分泌治疗的早期耐药密切相关。</td>
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                <td style="padding: 12px; border: 1px solid #cbd5e1; font-weight: 600; background-color: #fcfdfe; color: #546e7a;">靶向治疗突破</td>
                <td style="padding: 12px; border: 1px solid #cbd5e1; color: #334155; line-height: 1.6;">选择性 p110α 抑制剂（如 <strong>[[阿培利司]]</strong>）已获批联合内分泌治疗用于 PIK3CA 突变的晚期乳腺癌。此外，针对该靶点的新一代别构抑制剂和降解剂正处于临床研究中。</td>
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                <td style="padding: 12px; border: 1px solid #cbd5e1; font-weight: 600; background-color: #fcfdfe; color: #546e7a;">消化道肿瘤特征</td>
                <td style="padding: 12px; border: 1px solid #cbd5e1; color: #334155; line-height: 1.6;">在结直肠癌（约 15%-20%）和胃癌中也常见 PIK3CA 突变，常伴随 KRAS 突变或 MSI-H 特征。PIK3CA 状态被认为是抗 EGFR 单抗治疗反应的潜在负性预测指标。</td>
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                <td style="padding: 12px; border: 1px solid #cbd5e1; font-weight: 600; background-color: #fcfdfe; color: #546e7a;">检测技术规范</td>
                <td style="padding: 12px; border: 1px solid #cbd5e1; color: #334155; line-height: 1.6;">推荐使用 <strong>[[NGS]]</strong> 进行组织或 <strong>[[液体活检]]</strong>（ctDNA）检测。由于该突变具有时间与空间异质性，晚期患者在治疗进展后进行再次分子分型具有重要临床价值。</td>
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        <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span>
        
        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [1] <strong>André F, et al. (2019).</strong> <em>Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer.</em> <strong>New England Journal of Medicine</strong>.<br>
            <span style="color: #475569;">[点评]：SOLAR-1 研究，确立了阿培利司在 HR+ 乳腺癌中的地位。</span>
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            [2] <strong>Samuels Y, et al. (2004).</strong> <em>High frequency of mutations of the PIK3CA gene in human cancers.</em> <strong>Science</strong>.
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            [3] <strong>NCCN Guidelines Version 1.2025:</strong> <em>Breast Cancer - Management of PIK3CA-mutated HR+ tumors.</em>
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        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [4] <strong>Fruman DA, et al. (2017).</strong> <em>The PI3K Pathway in Human Disease.</em> <strong>Cell</strong>.
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        <p style="margin: 12px 0;">
            [5] <strong>中国专家共识 (2025修订版).</strong> <em>PIK3CA 突变晚期乳腺癌分子检测与靶向治疗专家共识.</em> <br>
            <span style="color: #475569;">[点评]：规范了检测平台选择、阈值判读与不良反应（高血糖）管理路径。</span>
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        <div style="background-color: #0f172a; color: #ffffff; text-align: center; font-weight: bold; padding: 10px; letter-spacing: 1px;">PI3K/AKT/mTOR 信号通路与致癌基因导航</div>
        
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                <th style="width: 20%; padding: 12px; background-color: #f1f5f9; color: #475569; text-align: right; font-weight: 600;">关联基因</th>
                <td style="padding: 12px; text-align: left; color: #1e40af;">[[AKT1]] • [[PTEN]] • [[mTOR]] • [[TSC1/2]] • [[PIK3R1]]</td>
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                <th style="width: 20%; padding: 12px; background-color: #f1f5f9; color: #475569; text-align: right; font-weight: 600;">临床癌种</th>
                <td style="padding: 12px; text-align: left; color: #1e40af;">[[乳腺癌]] • [[子宫内膜癌]] • [[结直肠癌]] • [[头颈部鳞癌]]</td>
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                <th style="width: 20%; padding: 12px; background-color: #f1f5f9; color: #475569; text-align: right; font-weight: 600;">核心技术</th>
                <td style="padding: 12px; text-align: left; color: #1e40af;">[[NGS]] • [[阿培利司]] • [[内分泌耐药分析]] • [[液体活检]]</td>
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            分类: [[遗传学]] | [[肿瘤学]] | [[致癌基因]] | [[精准医疗]]
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